Natural History of Early, Localized Prostate Cancer
Jan-Erik Johansson, MD, PhD
Ove Andrén, MD
Swen-Olof Andersson, MD, PhD
Paul W. Dickman PhD
Lars Holmberg, MD, PhD
Anders Magnuson, BSc
Hans-Olov Adami, MD, PhD
JAMA, June 9, 2004 – Vol 291, No. 22

Without understanding the natural history of prostate cancer diagnosed at an early, localized stage, patient counseling and clinical management are difficult. The challenge is to maximize the possibilities for survival without extensive over- treatment. Even without initial treatment, only a small proportion of all patients with cancer diagnosed at an early clinical stage die from prostate cancer within 10 to 15 years following diagnosis. However, to our knowledge, no study has hitherto adequately analyzed whether patients who escaped metastasis and death during those 10 to 15 years without treatment continue to have an indolent, nonfatal disease course or whether in the long term, tumor progression takes a more aggressive course. Recently, a randomized trial demonstrated that radical prostatectomy may further reduce the low-death rate in early prostate cancer by approximately 50%. Because it takes several years after operation for this benefit to emerge, age at diagnosis, comorbidity that influences life expectancy and long-term natural history will determine the potential ad vantage with radical primary treatment.

This study focuses on information that aids clinical decision making, namely the association between prognostic factors available at diagnosis and the long-term natural history in patients without initial treatment. Such knowledge can help us understand whether there are men with prostate cancer and a long life expectancy in whom early radical treatment might be justified despite the fact that they have favorable prognostic signs seen from a perspective of 5 to 10 years of follow-up. We studied these issues prospectively in the largest population-based cohort ever impaneled to analyze survival following watchful waiting of patients with early prostate cancer. Complete follow-up of this cohort has now been achieved during an average of 21 years, and only 9% of the patients are still alive.

METHODS
Patients
The patients comprised a population- based cohort of patients with early, initially untreated prostate cancer as previously described in detail. The TNM system and the World Health Organization classification of malignant diseases were used. At the time of diagnosis, all patients underwent a clinical examination, excretory urography, chest radiography, bone scan, and skeletal radiography (if needed) and had routine blood samples taken. The nodal status was not known for any of the patients. Prostate-specific antigen (PSA) testing was not available, and no screening activities for prostate cancer took place during the period when this cohort was recruited.

From March 1977 through February 1984, a total of 654 new cases of prostate cancer were diagnosed among residents in the regionally well-defined catchment area in central Sweden. Patients were given no initial treatment if the tumor growth was localized to the prostate gland as judged by digital rectal examination (T0-T2) and no distant metastases were present (306 patients). This was in accordance with the standard management at the time in Sweden. The following restrictions were applied, however, among those with palpable tumors (T1-T2). From March 1977 through February 1979, only patients with a highly differentiated tumor (grade 1) were included in the untreated group. From March 1979 through the end of the recruitment period, patients younger than 75 years at diagnosis and with moderately or poorly differentiated tumors (grades 2-3) were randomly allocated to receive local radiation (10 patients) or no treatment, and only the latter group was included in this cohort study. Patients 75 years or older were not treated and included in the study.

Among the 227 eligible patients, 4 (2%) were given initial treatment and had to be excluded from the analyses. The distribution of the study group of 223 patients by age, stage, and grade at the time of diagnosis is shown in TABLE 1. The mean age at diagnosis was 72 years (range, 41-91 years). Altogether 106 (48%) cases were detected by histopathologic examinations of specimens obtained at operations for suspected benign prostatic hyperplasia. The remaining 117 patients had a palpable clinical disease localized to the prostate gland. A review by an experienced histopathologist confirmed the initial diagnosis in all cohort members. Approximately two thirds of patients had highly differentiated tumors, whereas only 9 (4%) had a poorly differentiated tumor.

Procedures
All 223 patients were followed up from diagnosis until death or the end of the observation period (September 1, 2001). No patient was lost to follow- up. Clinical examination, laboratory tests, and bone scans were performed every 6 months during the first 2 years after diagnosis and subsequently once a year during the first 10 years of observation and thereafter at least once every second year. Those in whom the cancer progressed to symptomatic disease were treated with exogenous estrogens or orchidectomy.

Local progression was defined as tumor growth through the prostate capsule (T3) as judged by digital rectal examination. Development of distant metastasis (Ml) was classified as generalization. If both local progression and metastatic disease were present, the patient was classified as having generalized disease.

During the first 6 years of follow- up, all patients who were still alive and consented underwent a new fine- needle biopsy every other year. We obtained such biopsy specimens from 178 (80%) of the 223 patients. Although this procedure has lower than 100% sensitivity, notably for impalpable tumors, remaining cancer growth was confirmed cytologically in most patients:
45 (73%) among those with TOl disease, 24 (92%) among those with TOd disease, and 90 (100%) among those with T1-2 disease. Altogether 31(17%) of 178 patients showed evidence of de differentiation. Twenty-one patients (18%) changed from high to moderate differentiation, 7 (13%) from moderate to low differentiation, and 3 (3%) from high to low differentiation.

The medical records of all deceased patients were reviewed. In most in stances, the cause of death determined in real time was obvious on clinical grounds alone. An autopsy was per formed if the cause of death was not clear. Prostate cancer was recorded as the underlying cause of death, a contributory cause of death, or unrelated to death as described in detail in a previous re port. If treatment of the prostate cancer was related to death (chiefly due to cardiovascular complications following estrogen administration), prostate cancer was recorded as a contributory cause. As a validation, we compared our own classification of causes of death with those recorded in the Swedish Death Register. This information was obtained through record linkage between our study cohort and the Swedish Death Register based on the individually unique national registration number as signed to all Swedish residents. There was agreement in 90% of the patients and no evidence of systematic overascertainment or underascertainment of prostate cancer as cause of death in our data. Although based on small numbers, there was no evidence that the disagreement was larger in older than in younger patients.

Statistical Methods
We estimated various measures of patient survival using the actuarial (life- table) method. Cause-specific survival was estimated by considering only deaths due to prostate cancer as events of interest (deaths due to other causes were considered censored), observed survival by considering deaths due to any cause as events, and progression- free survival by considering progression as the event of interest. We also estimated relative survival, defined as the ratio of observed survival to the expected survival of a comparable group from the general population assumed to be free of prostate cancer. We estimated expected survival using the Hakulinen method based on Swedish population life tables stratified by age, sex, and calendar time. We also calculated prostate cancer—specific mortality rates (deaths per 1000 person- years at risk) and associated 95% confidence intervals (CIs). We estimated Poisson regression models to study the association between prostate cancer mortality and time since diagnosis while adjusting for age at diagnosis, stage, and grade. Relative survival was estimated using software developed at the Finnish Cancer Registry.’ All other analyses were per formed using Stata statistical software (Stata Corporation, College Station, Tex). All reported P values are 2-sided. Statistical significance was P<.05.

RESULTS
Overall Findings
During a mean observation period of 21 years, 89 patients (40%) experienced progression of disease, and of these 39 (17% of the entire cohort) developed generalized disease. A total of 203 patients (91% of the entire cohort) died during follow-up, with prostate cancer considered the cause of death in 35 (16% of the entire cohort; Table 1). Among patients who were 70 years or younger at diagnosis, 22 (22%) died from prostate cancer during follow- up, whereas this proportion de creased markedly at higher ages. The proportion of patients dying from prostate cancer was strikingly similar among those with nonpalpable (TO) tumors detected at transurethral resection (18 patients [ and those with a palpable tumor (17 patients [ In contrast, poor differentiation was a strong predictor of prostate cancer— specific death.

Progression and Survival Rates
Although based on small numbers, the progression and mortality rates remained fairly constant during the first three 5-year periods following diagnosis. Averaged over the first 15 years, the rate of progression to metastatic disease was 18 per 1000 per son-years (95% CI, 13-25) and the prostate cancer mortality rate was 15 per 1000 person-years (95% CI, 10-21). In contrast, an approximately 3-fold higher rate was found both for progression and death during follow-up beyond 15 years (Table 2). This increase was almost statistically significant for progression (P= .06) and statistically significant for death (P=.0l).

TABLE 3 shows various measures of survival after 15 and 20 years of follow- up. During this 5-year period, the progression-free survival among all patients decreased from 45.0% to 36.0%. The low and rapidly decreasing ob served survival reflects chiefly the impact of causes of death other than prostate cancer. Most notably, however, we found a substantial decline by approximately 25 percentage points in both the relative and the cause-specific survival rate during the last 5 years of follow-up. FIGURE 1 further illustrates how a gradual decline in relative and cause- specific survival seemingly occurred more rapidly after approximately 16 years of follow-up. This change seemed to affect tumors regardless of initial stage and also to affect tumors that were both initially highly and moderately differentiated. The gloomy outlook among patients with poorly differentiated tumors became manifested already within the first 5 years of follow-up.

Prostate cancer mortality was slightly higher among patients whose cancer was diagnosed at 70 years or younger than among those whose cancer was diagnosed at older ages (Table 2). Strikingly similar mortality rates were found among patients who had localized non- palpable cancer compared with those who had a cancer in stage Ti or T2. In contrast, the mortality rate was 70% higher among men with a nonpalpable diffuse cancer. With regard to differentiation, the mortality rate in creased drastically from highly to poorly differentiated tumors (Table 2).

Multivariable Analyses
Multivariable Poisson regression models were fitted to quantify the independent effects of follow-up time, age at diagnosis, grade, and stage (TABLE 4). Our analyses showed a significant (approximately 6-fold) higher mortality rate after 15 years of follow-up compared with the first 5 years. The strong prognostic impact of grade, notably of poorly differentiated tumors, was also con firmed. In contrast, neither age at diagnosis nor stage of disease was significantly associated with risk of death due to prostate cancer. Although we had limited power to test interaction, the risk of death due to prostate cancer after 15 or more years of follow-up com pared with 0 to 14 years was similar among patients with cancer diagnosed before (relative risk, 4.1) and after (relative risk, 3.1) 70 years of age.

A separate model was fitted in which the event of interest was local progression. In this analysis, we disregarded if and when regional and/or distant progression or metastases were ascertained. Except for age at diagnosis, the pattern for local progression was strikingly different from that of death due to prostate cancer (Table 4). Hence, the risk of local progression did not in crease over follow-up time, and the association with grade was weak. More over, compared with T0l tumors, growth beyond the prostate capsule was 2 or 3 times more likely in patients with T0d and T1-2 tumors, respectively.

COMMENT
Although our cohort of patients with early stage, initially untreated prostate cancer has been previously followed up in great detail during an average of 15 years, the additional 6 years included in this analysis revealed an un expected change in prognostic out look; the cause-specific survival rate de creased by almost 25 percentage points, reflecting an approximate 3-fold in crease in prostate cancer mortality rate compared with the first 15 years of follow-up. This change occurred consistently across stage and grade except for poorly differentiated cancers in which excess mortality becomes manifest al ready during early follow-up. We were unable to conceive of any bias that could have spuriously generated these recent findings. Indeed, the internal validity of our population-based study should be high because we achieved complete follow-up and used standardized procedures for clinical examination, ascertainment of disease progression, and classification of death. Moreover, the slight difference between cause-specific and relative survival estimates were largely consistent overtime. This argues against any shifting criteria for classification of cause of death, since the relative survival rate reflects excess mortality (compared with mortality in the general population) and is thus unaffected by any subjective judgment. Prostate cancer mortality rates were mirrored closely by rates of disease progression to metastatic disease. Hence, chance is the only realistic alternative to a real deterioration in prognosis after long-term follow-up, and the level of statistical significance argues against this explanation.

If our data reflect a real phenomenon, they would imply that the probability of progression from localized and indolent to metastatic mortal disease in creases markedly after long-term follow up. This progression is not restricted to cancers diagnosed due to clinical symptoms but includes also tumors detected incidentally at transurethral re section due to presumed benign prostatic hyperplasia. Our survival data, supported by biopsy specimens taken during follow-up, would further imply that these latter lesions are either incompletely removed or multifocal with malignant clones left at a trans urethral resection. Contrary to emerging views, our data also suggest that metastases may arise as a consequence of late mutations rather than being determined already by the early mechanisms of malignant transformation. According to a rival interpretation, the phenomenon we observed reflects transformation of new, more aggressive cancer clones rather than progression of those initially detected. Empirical testing of these complementary, but not mutually exclusive, theories seems difficult.

It may be difficult to validate our survival data in any new cohort study of watchful waiting since aggressive treatment of localized prostate cancer has become more routine now than it was 25 years ago when we started to assemble our cohort.’ Indeed, it has been estimated that approximately 60000 men undergo radical prostatectomy yearly in the United States alone, and the number performed annually in England increased nearly 20-fold between 1991 and 1999.’ This development toward treatment with a curative intent may further accelerate following recent documentation that radical prostatectomy reduces prostate cancer mortality by approximately 50%. Hence, support for our findings has to be found chiefly in existing studies of watchful waiting. Other such cohorts are, however, few and small, none of them are population based and prospective, and virtually no follow-up data are available be yond 15 years after diagnosis. Within these constraints, experience during the first 10 years after diagnosis is strikingly similar in existing cohorts of patients with early stage prostate cancer left without initial treatment, with a favorable course of the disease for men with highly or moderately differentiated tumors.

From a public health perspective, implications of late progression from early stage to mortal disease may not be significant because without PSA testing, average age at diagnosis of prostate cancer is so high that competing causes of death predominate (Table 1). Al though it is well established that an excess death rate continues long term in population-based cohorts of prostate cancer patients, these data do not enable distinction of deaths generated by patients initially diagnosed as having localized disease. In our entire cohort, 25 (11%) of 223 patients died from prostate cancer within 15 years of diagnosis and an additional 10 during subsequent follow-up until a time when only 9% of all patients in the cohort were still alive and therefore at risk of progression. Assuming that radical prostatectomy prevents approximately 50% of prostate cancer deaths, approximately 18 patients (8%) in our entire cohort (that is, 0.5 X 35) would have experienced a survival benefit, whereas the remaining 205 would not. However, among elderly men, reducing the risk of death from prostate cancer by a certain amount may have limited impact on their overall survival.

Our data may be important for counseling and clinical management of individual patients. Postponement of death is not the only treatment objective because local progression may create substantial suffering. Indeed, many of our patients experienced symptomatic local growth without generalized disease (Table 1), requiring treatment with estrogens or orchidectomy. Obviously, radical prostatectomy is a major procedure with substantial ad verse effects, chiefly impotence and incontinence. Because these complications are surprisingly well tolerated, many patients may prefer a radical prostatectomy even if prolonged survival is an uncertain consequence. Our data may be particularly relevant to otherwise healthy men diagnosed as having prostate cancer at an early age. If such patients are in their 60s or younger, disease progression that occurs after 15 or more years may be a real concern, arguing for early local treatment with a curative intent. In patients with a PSA-detected cancer, such counseling is, however, complicated by the fact that a lead time that cannot be individually determined has to be added to the approximately 15 years that may precede more rapid tumor progression.

One important and complicated question is how the findings of this study relate to the current era when many patients are detected by means of PSA testing. The results are directly relevant for patients with clinical disease diagnosed before the PSA era and also to preclinical disease detected at trails- urethral resection for presumed benign prostatic hyperplasia. Indeed, as shown in Table 4, these 2 categories of patients experienced similar risk of dying from prostate cancer. The natural history we have described reflects also what would happen among PSA-detected cancer if the lead time could be accommodated and the patients were left without early therapeutic intervention. How ever, a substantial proportion of PSA diagnosed cancers represents overdetection of subclinical disease. These cancers would never have surfaced clinically during the patient’s lifetime, either because they are indolent or because death occurs from competing causes before clinical manifestation of the malignancy. By definition, these cancers do not generate any mortality.

In conclusion, our data indicate that the probability of progression to a more aggressive and lethal phenotype may in crease after long-term follow-up of prostate cancers that are diagnosed at an early stage and initially left without treatment. These findings argue for early radical treatment of patients with long life expectancy. Not only would such surgical intervention potentially prevent deaths, it would also convey prevention from disability caused by lo cal tumor growth.

Author Affiliations: Departments of urology and Clinical Medicine (Drs Johansson, Andrén, and Andersson) and Statistical unit, Center for Clinical Research (Mr Magnuson), Orebro university Hospital, and Center for Assessment of Medical Technology (Drs Johansson and Andersson), Orebro, Sweden; Department of Medical Epidemiology and Biostalistics, Karolinska Institute, Stock holm, Sweden (Drs Dickman and Adami); Regional On cologic Center, University Hospital, Uppsala, Sweden (Dr Holmberg); and Department of Epidemiology and the Harvard Center for Cancer Prevention, Harvard School of Public Health, Boston, Mass (Dr Adami).

Corresponding Author: Jan-Erik Johansson, MD, PhD, Department of Urology, Orebro University Hospital, SE-701 85 Orebro, Sweden (lan-erik.johansson@orebroll.se).

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Waiting Time in Prostate Cancer
Alfred I. Neugut, MD, PhD
Victor R. Grann, MD, MPH
JAMA, June 9, 2004 – Vol 291, No. 22

The study from Johansson and Colleagues published in this issue of THE JOURNAL illustrates why oncologists often substitute the jargon of survival rates to sidestep using the magic word cure, which is really what’s on every patient’s mind. In this well- conducted investigation, the researchers complete more than 2 decades of follow-up for a cohort of more than 200 Swedish men with early-stage prostate cancer from before the prostate-specific antigen (PSA) era who were treated with watchful waiting. Earlier reports by Johansson et al documented the relatively high rates of recurrence and mortality for those with high-grade tumors and the relatively lower rates among those with low-grade tumors, extending up to about 15 yearn of follow-up! In the current article, the authors extend their follow-up to more than 20 years and find a surprising acceleration in the recurrence and mortality rates of the patients with low-grade tumors. The result is that more aggressive disease indeed occurs after 15 years of follow-up for these patients.

One lesson, of course, is that cure is only an abstract concept in certain types of cancer. Clearly, prostate cancer joins breast cancer in this arena. It is well known that 5-year survival in breast cancer is not adequate and that even after 10 and 20 years, women continue to experience recurrence, with no plateau in the survival curves. Prostate cancer, similar to breast cancer in many other respects, shares this common feature.

What is unusual, however, is not the continued progression to recurrence and mortality, but the acceleration. Why did this occur? One possibility is that new technology was introduced, including the use of PSA testing and computed tomography or magnetic resonance imaging, and so more prostate cancer recurrence was recognized than in prior years, a variant on the Will Rogers phenomenon” Because PSA testing became available with these radiologic techniques, disease that would have been unrecognized in the first 10 to 15 years (up to 1985 or 1990) of cohort follow-up would have remained unrecognized while becoming recognized in the finals or more yea of the study. Thus, there is not truly an acceleration in the occurrence of recurrence, simply an increased rate of its detection and diagnosis. Another possibility is that the recurrences represent a different clone of prostate cancer within the prostate, and not simply recurrence of the original prostate cancer. Since this initially untreated cohort of patients, followed up for 20 years, was treated for symptomatic progression of cancer with either estrogen therapy or orchiectomy, dedifferentiation of hormone-resistant cancers may have occurred. Furthermore, the use of estrogen therapy may have led to cardiovascular disease or thrombophlebitis, potentially fatal adverse effects of therapy that would have been attributed to prostate cancer.

Whatever the reason for the acceleration, this is the first study to have such long follow-up of a cohort with prostate cancer. As such, it has some relevance, as the authors state, for treatment. Although the 5-year survival rate is a valid metric for comparing the results of randomized clinical trials, the use of this outcome for a cohort of untreated patients across time or place may be misleading. The randomized trial of radical prostatectomy, also conducted in Sweden, had a 50% reduction in prostate cancer-specific mortality for the radical prostatectomy group compared with the watchful waiting group, with no significant improvement in overall morta1ity. However, the short follow-up time of this trial (ie, only 6.2 years) is not sufficient for the assessment of prostate cancer outcomes. Longer follow-up beyond 5-year survival is needed in this trial and in other studies to fully assess the real benefits of radical prostatectomy.

Also, the patient population in the current study by Johansson et al is, on average, 70 Years or older. Younger patients will need more aggressive treatment, particularly given the poor long-term outcomes and the increasing survival that they will have from other causes. Furthermore, because of their increased age and longevity, there may also be a survival bias because they have survived competing causes of mortality. As a consequence, all age-dependent causes of death will increase, especially for a disease such as prostate cancer.

Most important, this cohort was assembled prior to the advent of widespread PSA testing. What relevance and what implications do the findings have in the current era of PSA screening? Two ongoing studies of watchful waiting for patients with localized low-risk prostate cancer are measuring PSA levels and using PSA doubling times as an indication for therapeutic intervention. Screening, of course, adds lead time to the follow-up and thus the extent of follow-up before progression and mortality potentially will be even longer than this study shows.

These studies remain confusing in terms of their overall implications for prostate cancer screening. After all, one of the key questions in prostate cancer remains: Why isn’t it obvious that prostate cancer screening with PSA works? Many of the ingredients for successful screening have always been present in prostate cancer, such as an excellent potential screening test, good stage-specific survival, and down staging with use of the screening test. The incidence of prostate cancer increased dramatically in the United States starting in 1988, with a peak around 1992, but no clear-cut subsequent decline in prostate cancer mortality has occurred. The study by Johansson et al adds one more datum: the fact that long follow-up may be necessary to ob serve the full benefits of earlier diagnosis and treatment.

A major question has been whether the use of radical prostatectomy improves survival, a question addressed by the recent radical prostatectomy randomized trial from Sweden and by the Prostate Cancer Intervention Versus Observation Trial (PIVOT), now in progress. But perhaps one of the key problems is the one raised in this study, ie, the length of follow-up necessary to demonstrate a survival benefit. It is difficult to think in terms of conducting a randomized trial for screening with a horizon of 15 to 20 years, but perhaps that is exactly what will be necessary to really observe the impact of PSA screening on prostate cancer.

Author Affiliations: Department of Medicine and Hated Irving Con1 Cancer Center, College of Physicians and Surgeons, and the Department of Epidemiology. Mailman School of Public Health, Columbia University. New York, NY.

Corresponding Author: Alfred I. Neugut, MD, PhD, Division of Medical Oncology College of Physicians and Surgeons. Columbia University, 630W 168th St, MSPH 725, New York. NY 10032 (ain1@columbia.edu).

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Brachytherapy Guided by Fusion Images: Less Rectal Toxicity
Published in the July 2004 Volume 13 Number 7 issue of Oncology News International

SAN FRANCISCO—Rectal toxicity among prostate cancer patients who are treated with brachytherapy can be diminished by using information obtained from a fusion of two images to guide placement of the radioactive seeds within the tumor, Rodney Ellis MD, assistant professor if urology, Case Western Reserve School of Medicine, Cleveland, reported at the 99th Annual Meeting of the American Urological Association (abstract 1071).

Functional and anatomical image fusion has been rendered practical in recent years by the advent of more powerful computers. By superimposing a functional image that provides clues to cells’ disease status upon an anatomic image showing an individual patient’s prostate and surrounding area, it is possible to guide brachytherapy more precisely, Dr. Ellis said.

The functional, or cancer-detecting, image is obtained via scintography with ProstaScint (capromab pendetide), a monoclonal antibody to prostate-specific membrane antigen (PSMA) that is labeled with the radioisotope indium-III and then administered intravenously. This image is superimposed on a CT scan, which, by itself, provides a high-resolution image of pelvic and prostate anatomy but little or no information about the location of cancerous tissue.

Superimposition of the two images pinpoints tumor locations within the individual patient, potentially allowing more carefully targeted needle placement while minimizing unnecessary radiation exposure to the rectum, urethra, and bladder.

ProstaScint is FDA approved for imaging of prostate cancer patients at high risk of pelvic lymph node metastases or for whom there is a high clinical suspicion of occult metastatic disease. PSMA is expressed in many primary and metastatic prostate cancer lesions, and its expression in prostate cancer cells is generally unchanged or increased in patients treated with hormonal therapy.

Dr. Ellis and his colleagues first started treating patients with fusion-image-guided brachytherapy in February 1997. In 1998, they published results indicating that Prosta Scint uptake closely tracked with the presence of tumor tissue, as determined by biopsy. While subsequent reports have discussed the efficacy of this treatment approach, Dr. Ellis said, the current study is the first to provide detailed toxicity results.

In the current study, 65 low-risk, 43 intermediate-risk, and 24 high-risk prostate cancer patients between 41.5 and 81 years old (median age, 65) were treated with either brachytherapy alone (78 patients) or external-beam radiation therapy (EBRT) plus a brachytherapy boost (54 patients). Radiation Therapy Oncology Group (RTOG) bowel function questionnaires were administered to all patients before treatment and every 3 to 6 months thereafter.

Acute grade 1 rectal toxicities, namely increased frequency or change in the quality of bowel habits, occurred in 41.9% of patients, while 3.1% experienced acute grade 2 toxicities (diarrhea requiring medication, or discomfort requiring analgesics).

Rates of chronic grade 1 toxicities (mild diarrhea, cramping, or slight rectal bleeding) at 4, 7, 12 18, 21, and 30 months postimplant were 12.1% 11.3%, 14.0% 16.0%, 9.8%, and 83%, respectively. At equivalent observation intervals, rates of chronic grade 2 toxicities (moderate diarrhea or intermittent rectal bleeding) were 0.9%, 0.0%, 2.5%, 1.3%, 7.8%, and 4.2%.

There were no acute or chronic rectal toxicities above grade 2, and no patient required colonoscopy, fulguration, or blood transfusion.

While Dr. Ellis cautioned that the study contained no control arm, he noted that these preliminary toxicity results compare favorably with those of previously published studies. He and his colleagues are continuing to monitor patients for late toxicities.

Earlier reports by Dr. Ellis and his colleagues have described 4-year cure rates of 100% for 80 low- and intermediate risk patients treated with brachytherapy only. Five-year cure rates for 66 intermediate-risk patients treated with brachytherapy and EBRT ranged from 68.6% for those with at least three risk factors to 100% for those with only one risk factor. Dr. Ellis said these results are markedly higher than those of most other published series.

In about a year or so, he intends to publish results on an expanded patient population of 270 patients treated with fusion-image-guided brachytherapy.

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Cancer deaths down in U.S., report finds
First-ever drop in lung cancer among women
MSNBC staff and news service reports
Updated: 12:24 p.m. ET June 3, 2004

WASHINGTON - More Americans are surviving cancer for five years or more and deaths from cancer overall are steadily declining, according to the latest annual report on cancer published Thursday in the journal Cancer.

For the first time, fewer women are being diagnosed with lung cancer, the joint report from the American Cancer Society, Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries finds.

Not everyone is reaping the gains: Minorities still are more likely than whites to die from cancer, says the report.

Cancer remains the second leading cause of death in the United States behind heart disease. This year 1.368 million Americans will learn they have cancer and 563,700 will die of it.

The “Annual Report to the Nation on the Status of Cancer, 1975-2001” finds that cancer rates dropped 0.5 percent per year from 1991 to 2001, while death rates from all cancers combined dropped 1.1 percent per year from 1993 to 2001.

This is due to better prevention, screening that catches cancer early enough to treat it, and better therapies.

Drop in lung cancer among women
Most striking in this latest tally is what’s happening with the No. 1 cancer killer: Rates of female lung cancer diagnoses have declined about 2 percent a year since 1998, years after men began a similar improvement.

Smoking became common among men long before women, and the resulting lung cancer consequently struck men sooner.

Lung cancer remains the nation’s top-killing malignancy for both sexes, and the second most common cancer. But it slowly declined among men starting in the early 1990s as older smokers died and fewer young men took up the habit — a pattern doctors expect to eventually see in women.

The report says female death rates from lung cancer have leveled off, remaining virtually unchanged since 1995, the report says.

“The first-ever drop in lung cancer incidence rates in women is remarkable proof that we are making a difference in the number one cancer killer, and is powerful evidence that our successful efforts must continue,” said John Seffrin, chief executive officer of the American Cancer Society.

Nonetheless about 174,000 Americans will be diagnosed with lung cancer this year and 160,000 will die of it.

The report builds on one issued by the American Cancer Society alone in January, which also showed overall cancer diagnosis and death rates dropping across the United States.

Survival milestone
The report’s other new finding: More people are living at least five years after a diagnosis of most types of cancer.

Five-year survival is a major milestone for cancer patients, and the scientists found significant gains over the past two decades in how often that milestone was met.

The joint report compares five-year survival rates of cancer patients diagnosed between 1975 and 1979 to those diagnosed between 1995 and 2000.

For men, survival rates improved the most — more than 10 percent — for cancers of the prostate, colon and kidney, and for melanoma and leukemia.

For women, the biggest survival improvements came in colon, kidney and breast cancers.

What does that mean? Today, 99.3 percent of men diagnosed with prostate cancer will live five years, up from 70 percent in the 1970s. Five-year survival for breast cancer is 88 percent, up from 75 percent in the 1970s.

But that survival is strongly connected to how early cancer is caught, stressed co-author Brenda Edwards of the NCI’s cancer-control division.

The report found that patients with the most deadly forms such as lung, pancreatic or liver cancers were only a little more likely to survive.

The racial gap
When looking at all cancers combined, black men are 26 percent more likely to die of a malignancy than white men, and Hispanic men are 16 percent more likely than non-Hispanic whites, said the Cancer Society’s Jemal.

Black women are 52 percent more likely to die of cancer than white women, and Hispanic women 20 percent more likely, he said.

Much of the disparity reflects minorities’ poorer access to cancer prevention and early detection services, Jemal said.

But notable differences remain even when scientists examine people diagnosed at the same stage of cancer, said NCI’s Edwards.

Black women were more likely to die of breast cancer, even though that disease is more common among whites.

Access to the best treatment options probably plays a role, as may additional illnesses patients have that complicate cancer treatment, Edwards said. “It’s not one simple story as to what is our national cancer burden,” she cautioned.

Added Jemal: “We know much about cancer. We need to apply everything about cancer control equally to all populations.”

And almost every racial and ethnic minority was more likely than whites to die of cancer.

The Associated Press and Reuters contributed to this report.

Click here to view this article and others at the MSNBC web site.

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Cancer Survivors Parks Now in 20 Cities
By Jane Erikson
Published in volume XXVI No. 4 / February 25, 2004 of Oncology Times, pp 28,30

Twenty-six years ago, Richard Bloch was diagnosed with lung cancer and given three months to live. Ever since then, Mr. Bloch—the “R” of the H&R Block tax- preparation firm—has been spreading his message that “cancer does not mean death.”

To draw attention to his message, Mr. Bloch and his wife, Annette, started the R.A. Bloch Cancer Foundation, initially holding “Cancer Survivors Day” rallies to draw public attention to cancer patients as survivors. The rallies have been held each June since 1986, now in more than 700 cities throughout the United States, according to the foundation.

The Foundation (www.blochcancer.org) also operates a Cancer Hotline 800-433-0464 with 550 volunteers answering questions. More recently, the Blochs have been building cancer survivors parks in major cities around the country, including Chicago, Cleveland, Houston, Indianapolis, Kansas City, New Orleans, Omaha, Phoenix, and— most recently—Tucson.

Tucson’s Cancer Survivors Plaza is the 20th park the foundation has built. The goal is to build 50 parks through out the United States and Canada, in cities with populations of at least one million.

Each of the parks is built along streets where people can drive by every day and see a sign that says “Cancer Survivors.”

“People see the signs and they get the idea that cancer does not mean death,” Mr. Bloch said. “And then when their cancer is diagnosed, they will remember the park, and think of those words and feel hope.”

“I don’t think there is such a thing as an unbeatable cancer,” he said in an interview. “Attitude had a lot to do with my beating cancer. I was told I wasn’t going to live more than three months. But I was lucky enough to find the right doctors. I had tremendous support from my family, which is very important. I had a strong desire to live. I have a strong faith in God. A lot of people said prayers for me. You put it all together, and I lived.”

The Bloch Foundation covers the $1 million cost of building each park, and donates $100,000 for maintenance when the park is completed.

3 Basic Elements
Each of the 20 parks includes the same three basic elements.
• The first is sculpture designed by local and regiona1 artists that portray the theme “Cancer...There is hope.”
• Second is a “Positive Mental Attitude Walk,” built around a series of plaques engraved with inspirational messages such as “There is no cancer from which someone has not been cured” and “Cancer is the most curable of all chronic diseases.”
• The third element is a “Road to Recovery Walk,” which includes more plaques describing basic strategies for beating cancer.

Among the messages: “Eat a well-balanced diet to maintain an effective immune system” and “Find a qualified physician who believes you can be successfully treated .Do everything your physician suggests, and do everything you believe might help that your physician says will not hurt. You are the boss. This is your life.”

Complement Local Environments
Plans for each park are reviewed by the Blochs. Each park is designed to complement local environments.

Kansas City’s park features a massive arch of triumph. Omaha’s has 14 stainless steel columns designed to create a column of light. Houston’s park features carved stone work covered in wrought iron with a dome that holds 2,000 lights.

The park in Columbus features a large rotunda that looks out over the river that winds through the city. Chicago’s park features two highly visible granite columns on Lake Shore Drive.

Tucson’s 1.2-acre Cancer Survivors Plaza stands on the edge of the city’s central Reid Park. It features native plants, bright colors, a tiered fountain, and other painted tiles, which are all reflective of Mexican folk art. A steel ramada, laser-cut with intricate folk-art patterns, creates a movement of light and shadow that changes throughout the day and time of year.

Seven nearly life-sized bronze statues depict individuals—an elderly couple a young family, a woman running as if toward a finish line—making their way through an obstacle course that symbolizes cancer treatment.
Twenty-two plaques offer hope and information, and benches through out the plaza offer visitors the opportunity to relax and reflect.

Breast cancer survivor Beth Walk- up, wife of Tucson Mayor Bob Walkup, called the plaza “a celebration” for any one who has gone through or may be going through cancer treatment. “You can celebrate our lives every day here,” Mrs. Walkup said at the park’s dedication in early December.

Laurie Young, Director of Development and Communications for the Arizona Cancer Center, said Tucson’s new Cancer Survivors Plaza will play an important role in raising local awareness about cancer.

“It’s the kind of place people can go to find solace if they have lost some one to cancer or if they have cancer themselves, and that’s great,” Ms. Young said. “And if it reminds them to quit smoking and otherwise do what they can to protect themselves from cancer, that’s important too.”

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Prostate Cancer - Radiation After Surgery Helps Keep Prostate Cancer At Bay
By M.S.W., ZoeMed Inc. Copyright 2000, All Rights Reserved

Radiation therapy after surgery for men with prostate cancer lessens the chance of the cancer coming back, regardless of whether the radiation was administered immediately after surgery or after the cancer recurred, according to a new study in the June 2004 issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology.

Many studies recently have shown that radiation after surgery reduces the chances that the prostate cancer will recur. For prostate cancer, there are two main types of postoperative radiation therapy - adjuvant and salvage. Adjuvant is administered after the primary treatment (in this case, surgery) has been completed and it appears the cancer cells have been killed. Salvage is administered if prostate cancer has started to come back and the physician is trying to save the patient by treating the disease with radiation therapy. In this study, the researchers wanted to see which type of postoperative radiation therapy was best for men with prostate cancer. Between 1989 and 1997, 69 patients were referred for adjuvant radiation therapy and 88 patients with evidence of a recurrence were treated with salvage radiation therapy. The men in the salvage group received radiation, on average, 40 months after surgery while the patients in the adjuvant group were treated with radiation an average of three months post surgery. According to the study, salvage radiation therapy was significantly less effective when the patient’s PSA level rose over 1.

“The PSA level was the key factor in this study,” said Michael Hagan, M.D., Ph.D., the lead author of the study and a member of the Department of Radiation Oncology at the Medical College of Virginia Hospitals in Richmond.
“Today, practitioners follow prostatectomy patients very closely. As a result, salvage radiation therapy is usually initiated quite early. The results from both centers in the study were excellent when radiation treatment was initiated while the serum PSA level was less than 1 ng/ml.”

Dr. Hagan added, “This study shows that the policy for salvage radiation therapy is likely to be as effective as adjuvant radiation therapy only when the institution or practitioner monitors the patient’s PSA level very closely after prostatectomy.”
Cancer LifeCenter - Article 10029

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Radiation Therapy Effective for Some Men With Recurrent Cancer After Radical Prostatectomy
Published in the May/June 2004 edition of Coping With Cancer, pg 57

For men with prostate cancer who have had their prostate removed and later show signs of cancer recurrence, several factors can help predict response to subsequent radiation therapy, according to a study in a recent issue of The Journal of the American Medical Association.

Principal investigator Kevin M. Slawin, MD, of Baylor College of Medicine and The Methodist Hospital, Houston, and colleagues conducted a multicenter analysis of the outcome of salvage radiotherapy in a group of men with recurrence of prostate cancer after radical prostatectomy to identify variables that are associated with an effective response.

“On the basis of our results, we believe that patients with positive surgical margins who experience relapse after radical prostatectomy should be strongly considered for salvage radio therapy, even those with high-grade disease and/or a rapid PSA doubling time. We have developed a predictive model to estimate the likelihood of treatment success for a given individual that will help guide physicians in the selection of patients for this therapy,” the researchers write. “The clinical implications of our findings are that locally recurrent prostate cancer appears to be more common than previously reported, that it is frequently associated with aggressive features, and that salvage radiotherapy offers the possibility of cure for a substantial proportion of patients with a rapid PSA doubling time and high-grade cancer”

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Prostate Cancer in 15% of Men With Normal PSA
Best Test May Be to Follow PSA Levels Over Time, Expert Says
By Daniel DeNoon
Reviewed By Michael Smith, MD on Wednesday, May 26, 2004 WebMD Medical News

May 26, 2004 -- Fifteen out of every 100 older men with a normal PSA test actually has prostate cancer, a new study shows.

PSA --prostate-specific antigen –is a chemical marker given off by cells of the prostate gland. Suspiciously high PSA levels are often an early sign of prostate cancer. A PSA over 4 ng/mL usually means that a man will have to undergo needle biopsy of his prostate.

Men breathe a sigh of relief when their doctor tells them their PSA is normal. But some men with a low PSA do have cancer. Until now, it wasn’t clear how many, says researcher Charles A. Coltman Jr., MD, chair of the Southwest Oncology Group in San Antonio.

“Our study emphasizes that there is a range of PSA levels, from 0 to 4, across which a man can have prostate cancer,” Coltman tells WebMD. “There is not a clear cut cutoff based on PSA alone which allows you to define individuals who need to be biopsied.”

Driving home Coltman’s point is a dramatic picture. It shows a high-grade prostate cancer -- from a man whose PSA level was less than 1. The picture and the study it illustrates appear in the May 27 issue of The New England Journal of Medicine.

Individualized Prostate Cancer Screening
Coltman says that men and their doctors can no longer rely on PSA levels alone when deciding whether to have a prostate biopsy.

“The situation now is that the individual man with his individual urologist will have to assess what the person feels are his risk factors,” he says. “In consultation with his doctor, the individual man must come to grips with the question of whether or not a biopsy should be done. It will become a more personalized interaction.”

Who’s at high risk? Men with the following factors have the highest risk of prostate cancer:
• Age. A man’s risk of prostate cancer increases with age.
• Race. “African American men have the highest incidence of prostate cancer and the highest death rate from prostate cancer of any men in the world,” Coltman says.
• Family history. A man’s risk increases if his brother or father has had prostate cancer.

Prostate Cancer With a Normal PSA
In their study, Coltman and colleagues analyzed data from a clinical trial of nearly 10,000 men. After seven years, they had a prostate biopsy whether they had a high PSA or not.

About 3,000 of these men never had a PSA level of more than 4.0. Fifteen percent of these men tuned out to have prostate cancer. And 15% of these cancers were life-threatening, high-grade tumors.

The chances of prostate cancer -- and of high-grade cancer-- went up as PSA levels rose. But high- grade cancers were seen in men at all PSA levels.

Should Doctors Look for Trouble?
How hard should doctors look for prostate cancers? In an editorial accompanying the Coltman team’s study, Johns Hopkins researcher H. Ballentine Carter, MD, notes that a man’s lifetime risk of prostate cancer is 16%. Yet his risk of dying from prostate cancer is only 3%.

“In the age range of 60 years to 80 years, about 30% to 40% of men have small prostate cancers,’ Carter tells WebMD. “Now, this article tells us, we have the ability today to detect those.”

If doctors look harder for prostate cancers, they will find them. If they do this, a lot of men will have unnecessary surgery or radiation therapy. If they don’t, some men who might have been saved by early detection will die.

“We already know we are overdetecting the disease,” Carter says. “A lot of men who have prostate cancer are not going to have their disease harm or bother them during their lifetimes. Unless they were biopsied, they never would have known that they had prostate cancer during their life. The lower we set the PSA threshold, the more unnecessary treatments we’ll have.”

Like Coltman, Carter says a man’s risk factors for prostate cancer have to be taken into account. But he would be very careful about sending a man with a midrange PSA level to get a biopsy.

“If I met someone in their 60s at a PSA level of 2.5 or 3.0 or 3.5,1 would say, ‘Look, there is a high probability you do not have prostate cancer. Let’s monitor your PSA over time and see if it changes,” Carter explains. “There shouldn’t be any urgency to try to detect these tumors when PSA is in this range. These tumors grow very slowly. They still will be curable later when their PSA is 4.”

Carter warns that it’s a different story for men in their 40s. For them, a midrange PSA level may well mean trouble.

“These are the men we should be concerned about if they have a prostate level of 2.5 or 3,” he says.

Carter suggests that more important than a single PSA test is the speed at which PSA levels change over time. An increase of 0.5 nglmL to 0.75 ng/mL during the course of a year is worrisome, he says. Coltman, however, says he wonders whether most men would be comfortable waiting for a year to find out whether they have cancer.

Coltman and Carter agree that better tests for prostate cancer are sorely needed. These yet-to-be invented tests would find some marker on prostate cancer cells. It is hoped the marker would show not just that the cancer is there, but whether it is a cancer a man has to worry about.

“All of us men sit on a gland like that and we are all concerned,” Coltman says. “We are frantically engaged in attempts to understand the biology of prostate cancer. We frantically want to find markers that would not only be predictive of prostate cancer, but also would help identify those prostate cancers that are at high risk to go on and spread.”

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ARTICLE: The Emerging Role and Needs of Family Caregivers in Cancer Care
Written By: Myra Glajchen, DSW
Published in the March/April 2004 edition of The Journal of Supportive Oncology, pp 145-155

Abstract
Involvement of family caregivers is essential for optimal treatment of cancer patients in ensuring treatment compliance, continuity of care, and social support, particularly at the end of life. The diagnosis of cancer presents a major crisis not only to the patient but also to the patient's primary caregiver. Caregivers often assume this role under sudden and extreme circumstances, with minimal preparation and uneven guidance and support from the healthcare system. The primary setting for the delivery of care to patients with cancer has shifted from the hospital to the home as a result of increased use of outpatient services for cancer treatment, shortened hospital visits, longer survival, and the trend for caregivers to accommodate patients' desire to be cared for at home for as long as possible. Caring for a family member with cancer poses significant challenges, with considerable psychological and physical con- sequences for the caregiver. Family caregiving has gained attention in the past decade with growing realization that support for family care- givers benefits the caregiver, the patient, and the healthcare team. This article will attempt to provide an understanding of the multifaceted role of caregivers in cancer care, describe the impact of this role on the care- giver's quality of life, impart an understanding of the caregiver's burden and unmet needs, highlight adaptational requirements of caregivers along the disease trajectory, and describe interventions for providing support to nonmedical persons caring for patients with cancer.

The Emerging Role and Needs of Family Caregivers in Cancer Care
More than 15 million adults currently provide care to relatives with cancer in the United States. Caring for patients with advanced medical illness is a demanding role. As care has shifted from the hospital to the home, the role of the family caregiver has been transformed into a complex, multifaceted responsibility that many are ill prepared to assume.

One of the most important roles of the care- giver is assisting the cancer patient with pain management. Approximately 30%-45% of cancer patients experience pain in the early stages of the illness, and an average of 75% of patients with advanced cancer experience pain. Caregivers are expected to assess and report information regarding the patient's pain, including the source, nature, and amount of pain. They must identify and report side effects of the patient's therapy as well as new symptoms experienced by the patient. Care- givers are required to decide which medication to dispense, when to give it and at what dosage. They are frequently required to dispense pain medication or remind the patient to take a scheduled dose.

Caregivers are expected to keep records and control the technical aspects of pain management. They are expected to fill and refill pain prescriptions, which presupposes such skills as proficiency with insurance reimbursement, the ability to follow medical instructions, and the ability to anticipate the need for refills ahead of time. Technological advances in pain management require caregivers to engage in more complex care tasks, including managing patient-controlled analgesia pumps, epidural catheters, and home infusions -- responsibilities that can be terrifying for even the most sophisticated of caregivers. Nevertheless, involvement of family caregivers is essential for optimal treatment of cancer patients at the end of life, especially in ensuring treatment compliance, continuity of care, and social support.

Caregivers function as home health Rides and companions. They are expected to provide patients with emotional support, conversation, and other forms of distraction. They are asked to complete insurance forms, provide meals, arrange transportation, and provide personal care. The caregiver is forced to navigate the rapidly changing healthcare system, including obtaining information that can be difficult to find, managing payment requests, and paying bills.

Caregivers function as legal and medical assistants. The patient-family unit is expected to make decisions about treatment options, goals of care, advance directives, role changes, and finances. Care- givers manage home-care professionals; handle medical emergencies; facilitate transitions (eg, home to hospital to hospice or long-term care facility); obtain medical, financial, and legal advice; prepare for the patient's death; and arrange the funeral.

Clearly, caregivers of cancer patients have multifaceted expectations and needs. Unfortunately, the healthcare system does little to address caregivers' needs and concerns-they are automatically assumed capable of performing complex medical care tasks at home, their symptom management and coping skills are seldom appraised, and their own physical health is rarely considered.

Impact of Caregiving on the Caregiver's Quality of Life
The cancer experience affects not only the patient but also the caregiver, and in profound ways. Caring for a person with cancer is demanding and overwhelming and can be a stressful experience that may erode the physical and psychological health of the caregiver. Caregivers describe the experience of caring for a loved one who is near death as influencing many domains of life. The impact of pain on a caregiver's quality of life has been described as having four distinct dimensions: physical, psychological, social, and spiritual.

PHYSICAL IMPACT
Physical demands of caregiving are generally related to the patient's medical situation, including disease stage, symptoms, functionality, fatigue level, and side-effect profile. Cancer patients require various levels of support depending upon the stage of their disease; the more time required of the caregiver in doing tasks for the patient, the more disrupted will be the caregiver's schedule and emotional well-being. Caregivers who are providing 24-hour-a-day care often experience cumulative sleep disruption, and fatigue is common. From a physical and practical standpoint, caregiving has been described as relentless, marked by constant monitoring of the patient's medical condition, pro- vision of personal and nursing care, and assuming duties previously performed by the patient. Care- givers describe stress and strain that can parallel or surpass the patient's. In fact, at least one prospective population-based cohort study found that the strain of caring for a patient with cancer in- creased the caregiver's risk of mortality by 63% within 5 years.

PSYCHOLOGICAL IMPACT
Psychological demands of caregiving relate to anxiety, distress, and depression in both the patient and the caregiver. Caregivers have their own emotional responses to the patient's diagnosis and prognosis and may require coaching and emotional support separate and apart from the patient. When family caregivers undertake new and stressful responsibilities associated with caregiving, they experience profound psychological strain. Family members of seriously ill patients have been found to experience as much, or more, distress than even the patient suffers. This distress results from both the caregiver role and from witnessing the patient's suffering. Caregivers of patients with cancer-related pain report even higher levels of depression, tension, and mood disturbance than caregivers of pain-free patients. Over the long term, caregiving may result in serious depression, social withdrawal, and impaired quality of life.

Although most research has focused on the assessment of the negative psychological ramifications associated with caregiving, the psychological rewards and satisfaction of caregiving have also recently been recognized. One study found that levels of distress were reduced when positive feelings outweighed the negative feelings of care- giving. Another study demonstrated that home-based palliative caregiving resulted in life-enriching experiences for many caregivers, including opportunities for reciprocity, finding meaning in the situation, and spending time with the patient. Still another study found that in home- based family caregiver situations, positive bereavement outcomes predominated over negative reactions because the caregivers had an overall sense of having accomplished something difficult and extremely valuable.

SOCIAL IMPACT
The social demands of caregiving profoundly impact the caregiver's burden, especially with regard to relationship and financial factors. The characteristics of the relationship between patient and caregiver can have important ramifications. Approximately 70% of caregivers of cancer patients are spouses, 20% are adult daughters or daughters- in-law. and 10% are friends or extended-family members. If marital or relationship strain predates the onset of the patient's illness, the caregiver may approach caregiving grudgingly. Elderly spouses or spouses in need of assistance themselves may be more distressed by the patient's physical impairments owing to their age-associated health limita tions. For adult children who are fulfilling the caregiving role, juggling the demands of work, children, and spouses in addition to the demands of caregiving can be overwhelming.

The financial impact and economic costs associated with cancer also contribute to caregiver bur den. For patients with no insurance or inadequate insurance coverage, obtaining pain relief may be a struggle. Even patients with adequate insurance incur substantial financial burdens related to deductibles, co-payments, uncovered services such as transportation or home care, lost salaries and work, over-the-counter medications, household modifications, and alternative treatments such as herbs and vitamins. Limitations on the number of prescriptions allowed by some insurers, as well as monthly and refill limits, further contribute to the burden placed on caregivers.

SPIRITUAL IMPACT
Spiritual well-being has been increasingly recognized as an important factor for patients with cancer and their caregivers. Spirituality can have a profound influence on the distress, ability to cope, and quality of life of seriously ill patients and their family caregivers. While religion is defined as a specific set of beliefs and practices associated with a recognized religious denomination, spirituality is described as a construct that includes faith and meaning [18]. Spirituality encompasses experiential and existential aspects, such as a sense of peace and connectedness [19]. Spirituality has been de - fined as a thought process or belief system that al lows a person to experience a transcendent meaning in life—including the conviction that one is fulfilling a unique role and purpose in one’s life [20, 21].

A recent study evaluating quality of life, life satisfaction, and spirituality in patients with cancer or in patients undergoing rehabilitation found that spirituality was one factor among many associated with both life satisfaction and quality of life [22]. Other studies have also demonstrated relationships between spiritual factors and lower levels of anxiety and distress in cancer patients and between spirituality and experiencing a better quality of life. It has been proposed that spiritual beliefs and practices can enhance patients’ well-being through social support (sense of belonging) and improved coping strategies (higher self-esteem and sense of control over illness) [23]. Spiritual beliefs also may help patients and caregivers construct a meaningful framework fir their illness and result ant suffering, and this may promote acceptance of the situation [24].

Taylor [25] surveyed patients and their caregivers to determine their expectations with regard to having their spiritual needs addressed. The results of this survey supported the notion that many patients and caregivers were eager for spiritual care. Spiritual needs identified by participants in this study included kindness and respect; talking and listening; prayer; connecting with symmetry, authenticity, and physical presence; quality temporal nursing care; and mobilizing religious or spiritual resources.

Unmet Caregivers’ Needs
Despite the known adverse effects of family caregiving, the healthcare system does little to address caregivers’ needs and concerns. Unfortunately, in this era of high patient volume and brief patient appointments, caregivers may be acknowledged only briefly during the decision-making and discharge-planning portions of patients’ medical visits [Glajchen M, Kornblith A, Homel P, Fraidin L, Mauskop A, Portenoy RK. Development of a brief caregiver screening scale for caregivers of the medically ill (2003, in progress)]. Few practitioners or institutions provide effective programs for screening for caregiver burden or distress or for offering help when it is identified. Without proper support, caregivers face an extreme burden, both psychologically and physically.

To provide adequate emotional and physical support for the caregiver, the needs of caregivers, especially their unmet needs, must be appreciated. Caregivers of cancer patients frequently report un met needs in physical, psychosocial, economic, and instrumental domains, In a recent literature review, 60%—90% of patients and their caregivers were found to have a need for assistance in at least one area, with the needs most often reported by cancer patients and their caregivers being assistance with personal adjustment to illness (38%—70%),psycho- social support (30%—60%), transportation (31%.— 58%), financial assistance (50%—52%), home care (1O%—42%), and medical information (3%—29%) [26]. Between 18% and 30% of patients and care- givers reported that assistance for at least one need was unmet.

Other studies have also demonstrated a high degree of unmet needs for caregivers. In a study of terminally ill adults and their caregivers, 87% of patients reported unmet needs, with the most frequently cited being assistance with transportation (62%), homemaking services (55%), nursing care (29%), and personal care (26%). Most of the pa tients relied completely on family and friends to provide this assistance; only 15% relied on paid assistance 127]. For caregivers of cancer patients, such care may translate into 20 or more hours of care a week, the equivalent of an unpaid part-time job [ Before developing programs to meet care- givers’ needs, an assessment of their most pressing concerns is essential.

Cross-Cultural Considerations
Studies show that Hispanic and African- American patients and caregivers underutilize community health resources—counseling and support groups, home care, residential care, and hospice ser vices. The reasons for this underutilization are many. One important reason is that strong family ties may prevent minority caregivers from seeking help outside the family unit. Both Hispanic and African-American caregivers feel obligated to live close to their parents in order to provide assistance as needed [ In a 1996 study comparing African-American, Caucasian, and Hispanic caregivers, Guarnaccia and Parra [30] found that 65% of Hispanic patients and 60% of African-American patients lived with the family of their caregiver. The minority families relied more on informal caregiving front friends and relatives and had larger social support networks than the Caucasian families.

However, this increased sense of obligation to provide care for older family members is associated with more caregiving hours, greater resignation about caregiving, higher caregiver strain, and a larger reduction in household income than that re ported by Caucasian caregivers [31]. A study by Covinsky et al [32] analyzed reports of employment loss due to caregiving. Results showed that African-American and Hispanic caregivers were more likely than Caucasian caregivers to reduce their work hours to care for the patient. In addition, minority caregivers were reluctant to use for mal nursing homes services for their loved one. The decision to reduce work hours rather than place their relative in a nursing home was associated with increased psychological, social, and financial burdens.

In a recent landmark study, the impact of pain on Caucasians, African-Americans, and Hispanics was studied. Hispanics were less likely to know the cause of their pain than either of the other two groups. Hispanics were the least likely to visit a healthcare practitioner for their pain, which may not be surprising considering that, of the three groups, they were the least likely to have medical insurance, Hispanics reported having friends and family who were “very supportive” more often than did African-Americans. However, Hispanics were more likely to feel isolated, to say that pain had ruined their life, and to feel that they were not valued by their family and friends [33].

In the same study, factors that predicted disabling pain included an annual income of less than $25,000 and an educational level below that pf a high-school graduate. Although ethnicity was not a factor in predicting disabling pain, Hispanics and African were more likely than Caucasians to have lower in comes and lower levels of education, making them more at risk for disabling pain.

Accepting the burden of caregiving may lead to depression. Caregivers who have no outside help are more depressed than those who receive help from secondary informal caregivers or formal resources [29]. Despite reporting stress, many His panic and African-American caregivers do not seek outside help even when they are aware of support groups and other resources. The barrier to care may he a reluctance to share familial problems with outsiders. However, minority caregivers respond better to direct recruitment efforts through personal contacts and face-to-face inter views, strategies that are often too labor intensive for typical caregiver programs.

Similarly, underuse of hospice services has been reported in both the African-American and His panic communities. For African-Americans, barriers to hospice use include lack of availability, lack of community awareness, lack of trust in social ser vice providers, and misperceptions of the role of hospice services, Since African-Americans rely heavily on closely knit groups of friends and family, they are less inclined to welcome strangers, such as hospice workers, into their networks [34]. In addition, a prerequisite to hospice care is the presence of a primary caregiver in the home. Since African-American family members often have to work, no one is at home to care for the patient, and the patient may thus be barred from hospice care. Members of the African-American community may also he uncomfortable with the concept of palliative care, which seems to encourage the patient to give up and stop fighting [35]. These cross-cultural issues are important in assessing caregivers’ needs and in designing clinical and educational programs to meet those needs.

Adaptational Tasks at Different Points Along the Disease Course
The caregiver’s role and the burden of caregiving are profoundly affected by the cancer patient’s stage of illness and goals of care. Caregivers of patients receiving palliative care have been shown to have significantly lower quality-of-life and health scores than patients who are in active, curative treatment [35]. The physical and emotional demands of caregiving reach their peak as the disease progresses to the terminal phase. The period during which patients enter hospice is often characterized by profound unrest and intense strain. In addition to assuming many of the patient’s prior domestic responsibilities, family caregivers may have to forego social activities and work duties, resulting in job insecurity and isolation. Caregivers providing end-of-life care have been shown to experience increased emotional distress, regardless of the amount of care provided, when they are limited in their ability to participate in valued activities and interests [36]. Extensive research has shown that caregivers whose loved ones are receiving palliative care are at risk of developing a variety of psychological and physical problems, including anxiety, depression, fatigue, reduced self- esteem, and somatic health problems [11, 37, 38].

Recent studies have demonstrated that the caregiving experience affects the caregiver not only during the patient’s life hut also following the patient’s death, Inefficient psychological symptom control during the last months of a cancer patient’s life may predispose the surviving partner to long- term psychological morbidity [39]. In addition, the caregiver may he affected by the patient’s care, even after the patient has died. Bass et al [39] found that caregivers’ perceptions of the intensity and quality of support provided to the patient be fore death had a significant impact on their subsequent bereavement adjustment. In fact, the care- giver’s perception of the patient care he or she provided was more important for the surviving spouse’s or children’s adjustment than the support given directly to the caregiver during bereavement.

Assessment of Caregiver Quality of Life and Burden
Healthcare providers can he instrumental in providing direct assistance and referral to the care- giver so that patient care and caregiver well-being can he optimized. Several tools have been developed to assess caregiver quality of life [ and a brief caregiver screening scale to measure care- giver burden has recently been developed [Glajchen M, Kornblith A, Homel P, Fraidin L, Mauskop A, Portenoy RK. Development of a brief caregiver screening scale for caregivers of the medically ill (2003, in progress)]. Tools such as these can he used to assess caregiver functioning and to direct appropriate interventions. Because changes in patient- care needs and illness trajectory over time create different demands on the caregiver, the caregiver should he assessed at regular intervals throughout the course of the illness. The challenges faced by a caregiver at diagnosis or during an acute health crisis are dramatically different from the challenges faced as the patient nears the end of life.

Interventions for Caregivers of Cancer Patients
In response to the research conducted over the past two decades that has provided an understanding of caregivers’ roles and needs, several types of interventions have been developed with the goal of addressing these needs. In general, four types of interventions have been recognized as promoting the caregiver’s physical and emotional well-being: educational programs intended to increase care- givers’ knowledge; counseling or psychotherapy intended to reduce anxiety and depression; hospice or palliative home care intended to provide medical and psychosocial services for end-of-life care; and problem solving or skill building intend ed to improve skills and increase confidence.

EDUCATIONAL INTERVENTIONS
Education is an effective tool for helping cancer patients and their families understand the disease process, pain, other symptoms, and treatment options [46]. Information about the disease trajectory, the anticipated course, and the range of emotions experienced by families helps normalize the experience and enhances the sense of control that is often absent in cancer. The most important periods along the disease course for care- givers to receive information appear to be diagnosis, period of initial hospitalization, initiation of new treatments, recurrence, and the end-of-life phase [47]. However owing to the chronic nature of cancer and the range of tasks that need to he mastered at different points, caregivers’ information needs change over time [48].

Caregivers want factual information about cancer, its treatment, related symptoms, and side effects. They need specific details about what to do and how the particular cancer is likely to behave. In a recent survey of the information and education needs of cancer outpatients and their caregivers, the priority areas reported were [48]:
  • management of pain;
  • management of weakness and fatigue; and
  • the types of services available to facilitate patient care at home.

In the area of pain management, caregivers need to understand pharmacologic issues and medication instructions. Specifically, caregivers need instruction about which medications to use for pain relief, when to give the medication, how to assess the efficacy of pain control, how to monitor for side effects, arid how to identify negative results or ineffectiveness [49]. Caregivers have been shown to benefit from education in nonpharmacologic strategies for reducing pain, such as massage, use of lotions and ointments, and use of heat and cold compresses. Caregivers have responded favorably to education in distraction and relaxation techniques, as such skills promote caregiver confidence and reduce helplessness. Similarly, skills in positioning with pillows, mobilizing the patient, and assisting with ambulation in an effort to promote pain relief can be taught [49].

Especially important in cancer is the need to educate caregivers about alternative health practices that can exacerbate cancer pain and under mine treatment effectiveness. Toxic side effects, such as irreversible neuropathy, bleeding, and electrolyte imbalances, can result from alternative medical approaches to cancer treatment [50]. Desperate families may make erroneous decisions based upon misinformation in the media and on the Internet. Caregivers must be educated on the importance of reporting all alternative health practices to a healthcare provider. Importantly, caregivers must he educated about the support services that are available to them. Several studies have shown that patients and caregivers underutilize available resources owing to perceived lack of access, lack of information, or emotional exhaustion.
Unfortunately for caregivers, studies of doctor- patient communication show that medical issues tend to dominate, physicians tend to drive the discussion, and systems obstacles, such as lack of time, lack of space, and fragmentation in care, further hinder information exchange [48].

The role of family caregivers in fostering or hindering treatment compliance should not be under estimated. Caregivers’ knowledge and attitudes about pain management may influence the patient. If caregivers harbor fears of addiction, overdosing, or indirectly causing discomfort through side effects, they may guard the pain medication supply, limit its use, and undermedicate the patient [51]. Caregivers need training in the management of side effects, as side effects can cause patients to abandon the pain-treatment protocol prescribed for them. Educating caregivers about anticipated side effects and strategies for their amelioration is therefore essential.

COUNSELING OR SUPPORT INTERVENTIONS
Counseling or group-support intervention efforts are generally designed to enhance morale, self-esteem, coping, and sense of control while reducing anxiety and depression. Caregivers with low levels of emotional support have been identified as being more depressed over time [52]. Caregivers may be better equipped to meet their challenges if given the opportunity to discuss common problems and fears with healthcare professionals or others in a similar situation. Support groups, which promote information exchange and informal networking, appear to be most useful for providing social sup port for caregivers who are receptive to this type of assistance. Some caregivers, however, prefer individual counseling by clinicians whom they may recognize as “the experts.” Caregivers with psycho logical issues may respond best to individual counseling.

HOME HOSPICE AND PALLIATIVE CARE INTERVENTIONS
Hospice care involves a team-oriented approach for providing emotional and spiritual support for the patient and family, as well as offering expert medical care and pain management. Generally, this care is provided in the patient’s home or in a home-like setting. Palliative care is a medical specialty with the goal of extending the principles of hospice care to a broader population that could benefit from this type of care earlier in the disease process. Both hospice and palliative care focus on providing equal attention to the physical and psychosocial aspects of care, and both involve the patient and caregiver as the unit of care.

As patients become more debilitated, the demands for nursing care, social support, financial resources, and spiritual care increase considerably. Caregivers of palliative care patients report an increased need for time for themselves away from the home and time for their own personal needs [53]. Many caregivers report insufficient time to rest and inadequate sleep. To address caregivers’ needs for respite and personal time, the use of volunteers and short-term admission to inpatient facilities are useful. At this stage in the disease, care- givers should be instructed in methods of helping patients maintain some independence. Effective coping strategies reported by caregivers of home hospice cancer patients include learning more about the problem at hand, keeping busy, thinking positive, and talking about the problem with family and friends [54].

PROBLEM-SOLVING AND SKILL-BUILDING INTERVENTIONS
Throughout the caregiving process, caregivers assume a variety of new and complex roles and frequently lack the requisite resources or skills to undertake these roles. Nine core caregiving processes have recently been identified (Table 1) [55].

Mastery of each of these skills can be daunting for caregivers; therefore, interventions designed to help caregivers master these skills should he employed.

The most widely recognized and well-studied educational model for problem solving and skill building for caregivers is the Creativity, Optimism, Planning, and Expert information (COPE) program [56]. This program is designed to maximize care- givers’ effectiveness, sense of efficacy, and satisfaction through its four components. Models such as the one offered by COPE may empower caregivers and patients in coping with illness and can help moderate caregiver stress.

The Role of the Healthcare Team
Caregiving for a family member with cancer is a multifaceted, dynamic endeavor that has a pro found impact on the caregiver’s well-being, the patient’s care, and the treatment plan as a whole. Each member of the healthcare team has a role to play in meeting the needs of caregivers.

PHYSICIANS
Emanuel et al [27] found that caregiver bur den was significantly reduced by physicians who practiced “active listening.” In addition to listening attentively and proactively, oncologists are encouraged to provide information about the disease, its expected course, resources for pain management, and expected side effects of treatment.

In the absence of accurate information, patients and caregivers are more susceptible to misinformation from informal sources. Accurate information helps to reduce uncertainty and empowers care- givers by giving them a sense of control. In addition, caregivers derive emotional support from time spent with the healthcare professional. In general, caregivers report needing information about their loved one’s cancer, symptom etiology, what to expect in the future, treatment side effects, and management of medical emergencies [51].

NURSES
Nurses can play a role in integrating caregivers into the care plan by reinforcing medical education efforts and promoting an active role for caregivers in the care plan. Education for caregivers about the causes of cancer pain, the rationale for selecting a treatment approach, providing around- the-clock dosing for pain management, knowing what side effects to anticipate, and the treatment of those side effects should become a routine part of medical practice. In addition, most caregivers report that they discover nonpharmacological pain-management techniques informally or by trial and error. A brief instructional session by a nurse, rein forced with materials in print or electronic form, can serve as a catalyst for implementing these techniques and provide guidance for the proper use of heat, cold, massage, positioning, imagery, distraction, and other techniques [57].

SOCIAL WORKERS
Social workers can provide caregivers with guidance and information on the physical care of cancer patients; selection of home health aides; and accessibility to respite programs, counseling, sup port groups, financial assistance programs, and other resources [5]. They can provide counseling on illness adjustment issues and evaluate distress, coping, and the quality of life of both patient and caregiver, as well as the quality of the patient caregiver relationship. Referral to a psychologist or psychiatrist may he indicated for highly distressed caregivers. In addition, the social worker is adept at addressing the financial realities of treatment arid providing guidance in negotiating the healthcare system, a task that can become over whelming for overburdened and fatigued caregivers [58]. Costs associated with cancer include co payments, deductibles, and out-of-pocket costs for over-the-counter medications, as well as hidden costs arising from transportation, tolls, parking, nondrug medical supplies, environmental modifications, dietary needs, and lost wages [46].
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Table 1
Nine Core Caregiving Processes
1 Monitoring (ensuring changes in the patients condition have been noted)
2 Interpreting (making sense of what is observed)
3 Making decisions (selecting a course of action)
4 Taking action (carrying out decisions and instructions)
5 Providing hands-on care (carrying out nursing and medical procedures)
6 Making adjustments (progressively refining caregiver’s actions)
7 Accessing resources (obtaining what is needed)
8 Working together with the patient (sharing illness-related care in a way that is sensitive to the personalities and individuality of both patient and caregiver)
9 Negotiating the healthcare system (ensuring patients needs are adequately met)
Source: Schumacher et al [55]
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CHAPLAINS
Finally, the healthcare team’s chaplain can assess the role of religion and spirituality within the family, provide spiritual counseling, and guide other team members in strategies to address spiritual concerns and distress. Advanced-stage cancer—with its higher physical-symptom burden, greater distress, and reductions in quality of life and coping ability—may intensify spiritual and religious concerns [59]. Most patients want their spiritual needs and preferences to be addressed by their physicians [ Because these preferences may play a strong role in end-of-life decision making, they should become an integral part of all cancer treatment.

In sum, the social, psychological, and emotion al aspects of caregiving for the patient with cancer should he identified and supported by the entire healthcare team. Recognizing the psychological vulnerability among caregivers of cancer patients throughout the trajectory of the illness is essential in implementing specific interventions to promote coping, alleviate anxiety, and encourage problem solving.

End Article - For References Please Visit The Journal of Supportive Oncology

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The American Cancer Society estimates that during 2003 about 220,900 new cases of prostate cancer will be diagnosed in the United States. Prostate cancer is the most common cancer, excluding skin cancers, in American men. Prostate cancer is the second leading cause of cancer death in men in the United States, exceeded only by lung cancer. The American Cancer Society estimates that 28,900 men in the United States will die of prostate cancer during 2003. Prostate cancer accounts for about 10% of cancer-related deaths in men.

• Among men diagnosed with prostate cancer, 97% survive at least 5 years, 79% survive at least 10 years, and 57% survive at least 15 years. These figures include all stages and grades of prostate cancer but do not account for men who die from other causes.


• Eighty-five percent of all prostate cancers are found in the local and regional stages (local means it is still confined to the prostate; regional means it has spread from the prostate to nearby areas, but not to distant sites such as other organs). The 5-year relative survival rate for all of these men is nearly 100%.


• Of the roughly 6% of men whose prostate cancers have already spread to distant parts of the body at the time of diagnosis, 34% will survive at least 5 years.

(Information provided by the American Cancer Society)

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An article that appeared on WebMD in June, 2003 asked the question, "Why would a healthy man worry about prostate cancer?" After skin cancer, prostate cancer is the most common cancer in American males. Men's risk of getting prostate cancer is 16.7% however prostate cancer grows very slowly. Many men who have prostate cancer never know about it and usually die from something other than the cancer. Currently, early detection is the best way to prevent prostate cancer. Doctors advise men older than 50 to have annual digital rectal exams and PSA tests. However, men who are at a higher risk, particularly black men need to begin their annual screening at age 40.

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In September 2003 WebMD reported that the number of Americans that die from the four most common types of cancers is continuing to decrease. The report went on to show that as of the late 1990's the death rate for all cancers began to stabilize. Deaths due to prostate cancer have declined since 1994, but the rate of new prostate cancers has grown by 2-3% a year since 1995. From 1996 to 2000, the number of new prostate cancers was 66% higher among black men than white men. The report credits cancer screening for much of the gain of the new cancer cases, as well as the decline of cancer death rates.

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A study has shown that men who work with pesticides may have a slightly higher risk of prostate cancer than others. New research is showing that men whose job exposes them to high levels of pesticides have a 13% higher risk of prostate cancer than those with low levels of pesticide use. These findings were based on a study conducted from 1995 to 2001. This study was posted in the Journal of Occupational and Environmental Medicine.

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In the October 2003 issue of Oncology Times, Professor Richard Peto commented that "Suddenly in the 1990s death rates from breast cancer and prostate cancer turned around and started to drop," and a statistical analysis of the data from dozens of trial over 40 years indicates that the main reason is the introduction of hormone therapy, although earlier detection and better local control of