American Cancer Society prostate cancer survivorship care guidelines.

Prostate cancer survivors approach 2.8 million in number and represent 1 in 5 of all cancer survivors in the United States. While guidelines exist for timely treatment and surveillance for recurrent disease, there is limited availability of guidelines that facilitate the provision of posttreatment clinical follow-up care to address the myriad of long-term and late effects that survivors may face. Based on recommendations set forth by a National Cancer Survivorship Resource Center expert panel, the American Cancer Society developed clinical follow-up care guidelines to facilitate the provision of posttreatment care by primary care clinicians. These guidelines were developed using a combined approach of evidence synthesis and expert consensus. Existing guidelines for health promotion, surveillance, and screening for second primary cancers were referenced when available. To promote comprehensive follow-up care and optimal health and quality of life for the posttreatment survivor, the guidelines address health promotion, surveillance for prostate cancer recurrence, screening for second primary cancers, long-term and late effects assessment and management, psychosocial issues, and care coordination among the oncology team, primary care clinicians, and nononcology specialists. A key challenge to the development of these guidelines was the limited availability of published evidence for management of prostate cancer survivors after treatment. Much of the evidence relies on studies with small sample sizes and retrospective analyses of facility-specific and population databases.

Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial.

OBJECTIVE: To explore the prognostic and predictive value of baseline variables in 512 patients with metastatic castration-resistant prostate cancer from the phase III Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial who were randomized to receive sipuleucel-T or control. METHODS: The most powerful of these prognostic factors, baseline prostate-specific antigen (PSA), was subdivided into quartiles to evaluate treatment effect patterns. Cox regression analyses were used to assess predictors of overall survival (OS) and sipuleucel-T treatment effect within PSA quartiles. Median OS was estimated by the Kaplan-Meier method. RESULTS: PSA was the strongest baseline prognostic factor (P <.0001). Furthermore, the sipuleucel-T treatment effect appeared greater with decreasing baseline PSA. The OS hazard ratio for patients in the lowest baseline PSA quartile (≤22.1 ng/mL) was 0.51 (95% confidence interval, 0.31-0.85) compared with 0.84 (95% confidence interval, 0.55-1.29) for patients in the highest PSA quartile (>134 ng/mL). Estimated improvement in median survival varied from 13.0 months in the lowest baseline PSA quartile to 2.8 months in the highest quartile. Estimated 3-year survival in the lowest PSA quartile was 62.6% for sipuleucel-T patients and 41.6% for control patients, representing a 50% relative increase. CONCLUSION: The greatest magnitude of benefit with sipuleucel-T treatment in this exploratory analysis was observed among patients with better baseline prognostic factors, particularly those with lower baseline PSA values. These findings suggest that patients with less advanced disease may benefit the most from sipuleucel-T treatment and provide a rationale for immunotherapy as an early treatment strategy in sequencing algorithms for metastatic castration-resistant prostate cancer.

A decision aid for teaching limitations of prostate cancer screening.

There is minimal research regarding men's knowledge of the limitations of prostate cancer screening. This study measured knowledge of prostate cancer screening based on exposure to one of two decision aids that were related to prostate cancer screening (enhanced versus usual care). The sample consisted primarily of low income (54%) African-American men (81%) (n=230). The enhanced decision aid was compared against the usual care decision aid that was developed by the American Cancer Society. The enhanced decision aid was associated with higher post-test knowledge scores, but statistically significant differences were observed only in the men who reported having had a previous DRE (p = 0.013) in the multivariable analyses. All the men were screened, regardless of which decision aid they received. This study highlights the impact of previous screening on education of the limitations of prostate screening, and challenges the assumption that increased knowledge of the limitations of prostate cancer screening will lead to decreased screening.

Do "rapid" PSA assays reduce anxiety and stress of prostate cancer patients undergoing regular review? A prospective evaluation.

OBJECTIVES: Waiting for prostate-specific antigen (PSA) results may create anxiety for patients. Recently developed "rapid" PSA assays have become available, which achieve laboratory sensitivity and specificity. The manufacturers claim these assays will help to reduce anxiety associated with PSA testing. The aim of this study was to test the hypothesis that rapid received PSA results reduce patient anxiety. METHODS: One hundred eighty-eight (n = 188) patients participated in a prospective randomized study. After obtaining informed consent, 67 patients were assigned to receive PSA results within 15 minutes of the blood sample being drawn, facilitating a discussion with the physician while in-clinic. One hundred twenty-one (n = 121) patients were assigned to receive their results within 1 to 4 days by telephone. Patients completed a baseline questionnaire about PSA testing and a follow-up questionnaire after they had received their PSA result by either method. RESULTS: There were no significant differences in patient demographics between the "rapid" and "delayed" PSA test groups. Baseline measurements of stress and anxiety were low and not significantly different between the groups. Receiving a rapid PSA result did not significantly reduce stress and anxiety compared with a delayed result. However, 89% of patients receiving a rapid result would elect to have this method again. CONCLUSIONS: The rapid PSA test did not prove to alleviate stress or anxiety associated with receiving results. However, the cohort assigned to the rapid PSA test would prefer to have their results rapidly to facilitate discussion regarding their future management.

Combined androgen blockade in advanced prostate cancer: looking back to move forward.

In 1989, Crawford and colleagues suggested that combined androgen blockade with castration plus antiandrogen therapy provided significantly improved survival compared with castration alone. Since then, some studies have supported these results, whereas others have not. To resolve this discrepancy, the Prostate Cancer Trialists' Collaborative Group conducted a metaanalysis of 27 randomized trials to evaluate whether combined androgen blockade has benefits compared with castration alone. The results published in 2000 showed that combined androgen blockade using a nonsteroidal antiandrogen treatment (nilutamide or flutamide) improved survival compared with castration alone, whereas combined androgen blockade using a steroidal antiandrogen agent (cyproterone acetate) reduced survival compared with castration alone. In 2004, an analysis was carried out to evaluate the nonsteroidal antiandrogen agent bicalutamide in the combined androgen blockade setting, by incorporating the data from a trial of combined androgen blockade with bicalutamide versus combined androgen blockade with flutamide with the Prostate Cancer Trialists' Collaborative Group metaanalysis data for combined androgen blockade with flutamide versus castration. This analysis showed that combined androgen blockade with bicalutamide was associated with a 20% reduction in the risk of death compared with castration alone. The survival benefit associated with combined androgen blockade using a nonsteroidal antiandrogen agent should be weighed against the potential for increased toxicity and expense compared with castration alone. Studies have shown that bicalutamide has a better tolerability profile than flutamide or nilutamide. Furthermore, cost-benefit analyses of combined androgen blockade with bicalutamide suggest it is a cost-effective option versus castration alone and versus combined androgen blockade with flutamide. In summary, the present evidence suggests that combined androgen blockade with a nonsteroidal antiandrogen agent should be a first-line therapy option in patients with advanced disease.

Assessment of American urologists' approach to hormonal management of prostate cancer.

OBJECTIVES: To examine how American urologists are treating patients with prostate cancer who may benefit from hormonal therapy. Hormonal therapy has been shown to improve survival in patients with prostate cancer in an increasing number of clinical situations. METHODS: Questionnaires consisting of four case scenarios were sent to 1000 randomly selected American urologists. We compared the responses to the questionnaires with the current best evidence as guided by well-designed randomized controlled trials. RESULTS: Of the 181 urologists who responded, only 35% of questions were answered correctly according to evidence-based data. Thirteen percent of respondents answered more than two questions correctly. The number of years spent in practice, the type of practice, and the number of men treated with hormonal therapy did not affect the results. CONCLUSIONS: The results of our study have shown that in a select group of clinical scenarios regarding the use of hormonal therapy for prostate cancer, urologists infrequently chose the treatment option that reflects the results of randomized controlled trials.

Prostate cancer: epidemiology, screening, and biomarkers.

Carcinoma of the prostate continues to be a major health problem in the United States. Beginning in 1988, a marked increase in detection of prostate cancer occurred due to the development of a test for prostate-specific antigen (PSA). Controversy exists, however, about the value of PSA as a tumor marker. Although it has prognostic significance both before and after definitive therapy for prostate cancer, it is unclear whether routine PSA screening will translate into a survival advantage for patients. Because of its limitations, PSA may not ultimately be a good enough marker to be used as a screening tool. However, molecular biology has led to a rapid rise in the number of potential new prostate tumor markers, which may eventually overcome the weaknesses of PSA. Considerable progress has occurred in the diagnosis and management of prostate cancer: more is understood about the risk factors for the disease, possible ways to prevent it, and new ways to diagnose and monitor it. These developments have already translated into better patient care, while also identifying where further improvements are needed.

The bicalutamide 150 mg early prostate cancer program: findings of the North American trial at 7.7-year median followup.

PURPOSE: We describe the results of North American Trial 23 of the bicalutamide (Casodex) early prostate cancer program in the context of the overall early prostate cancer program findings. MATERIALS AND METHODS: In Trial 23, 3,292 men with T1b-4, N0-Nx (N+ not allowed) M0 prostate cancer who had undergone radical prostatectomy or radiotherapy at 96 specialist referral centers in the United States (2,974) and Canada (318) were randomized 1:1 to 150 mg bicalutamide daily or placebo in addition to standard care for 2 years. RESULTS: In Trial 23 at a 7.7-year median followup there were few clinical events in the bicalutamide or standard care groups and the rates of objective progression were 15.4% and 15.3%, respectively. Mortality rates were 12.9% in the treatment group and 12.3% in the standard care group, including 11.2% and 11.0% for nonprostate cancer deaths in the absence of objective progression and 1.6% and 0.9%, respectively, for mortality due to prostate cancer. No differences in the primary end points (objective progression-free and overall survival) were seen between patients treated with bicalutamide and those treated with standard care alone. Bicalutamide (150 mg) significantly improved time to PSA progression (HR 0.80, 95% CI 0.72 to 0.90, p <0.001). The tolerability profile of bicalutamide was similar to that previously described. CONCLUSIONS: In Trial 23 the current data suggest that early or adjuvant therapy may not benefit patients at low risk for recurrence, such as those with localized disease. The findings of Trial 23 contrast with the results in the overall early prostate cancer program and in other published literature, in which bicalutamide has been shown to provide significant clinical benefit for locally advanced disease.

[Usefulness and positioning of MAB therapy for prostate cancer].

Prostate cancer is a relatively slow-growing disease compared to other cancers, and the patients tend to be older. Taking into consideration therefore life expectancy of the patients and risks of recurrence and progression, conservative treatments (mainly hormonal therapy) are often applied for early cases, as well as radical treatments (total prostatectomy and radiotherapy). Particularly in Japan, many patients start treatment with hormonal therapy alone, in both early and advanced cases. Hence, Maximal Androgen Blockade (MAB) therapy, in which surgical or medical castration (such as LH-RH agonist treatment) and anti-androgen treatment are combined, is widely exercised with the hope to enhance treatment effects. The usefulness of MAB therapy has been assessed in a number of randomized comparative studies, covering mainly metastatic cases. The efficacy of the therapy with the use of flutamide as non-steroidal anti-androgen has been confirmed in some of the studies, although the magnitude of the efficacy cannot be said major. In Phase III clinical studies of MAB therapy with bicalutamide being conducted in Japan for patients in Stages C and D, however, the patient group treated with MAB therapy demonstrated more favorable results compared to the group treated with LH-RH agonist alone, particularly in terms of time to progression (TTP) of the patients in Stage C. These are relatively new findings on the usefulness and adaptability of MAB therapy. In this Panel Discussion, views and experiences are exchanged on a wide variety of topics covering the real usefulness of MAB therapy, its adaptability, possible outcomes of hormonal therapy in early cases, and the future of MAB therapy, taking into account the prevailing opinions and current practices on prostate cancer in both the United States and Japan.

Maximum androgen blockade: a clinical update.

Maximal androgen blockade (MAB) therapy for metastatic prostate cancer has advanced in recent years with the discovery of luteinizing hormone-releasing hormone agonists (LHRH), the development of LHRH analogues, and the discovery of antiandrogens. Of 36 studies of MAB therapy performed from 1980 to 1991, 3 showed a statistically significant increase in survival with MAB versus castration alone. Because of the large number of studies showing no benefit from MAB, a meta-analysis was performed on 27 studies. This meta-analysis demonstrated a survival benefit from MAB of only 3%; however, a critical review of the analysis revealed major flaws that raise serious questions regarding the validity of its findings. In addition, the fact remains that the longest survival reported for patients with stage M1 prostate cancer was 35 to 36 months, whereas the longest survival for castration alone was 32 to 33 months. Therefore, when physicians discuss treatment choices for patients with metastatic disease, MAB should remain a reasonable option.

The role of 111indium-capromab pendetide imaging for assessing biochemical failure after radical prostatectomy.

PURPOSE: Conventional imaging modalities, such as computerized tomography and magnetic resonance imaging, lack sensitivity and specificity for detecting recurrent prostate cancer after radical surgery. We evaluated the role of the indium-capromab pendetide scan, otherwise known as the ProstaScint (Cytogen Corp., Princeton, New Jersey) scan, in this setting. MATERIALS AND METHODS: A retrospective review was performed of 42 patients undergoing ProstaScint imaging for biochemical progression after radical prostatectomy. Of these patients 16 (38.1%) subsequently completed a course of salvage radiation therapy. RESULTS: Median prostate specific antigen (PSA) immediately prior to ProstaScint imaging was 1.2 ng/ml (range 0.2 to 4.8). Abnormal accumulation on the ProstaScint scan was detected in 36 patients (85.7%). Of the 16 patients undergoing salvage radiation therapy 15 had uptake isolated to the prostatic fossa on ProstaScint imaging. Ten of these 15 patients (66.7%) achieved undetectable PSA after radiation therapy, while 5 (33.3%) had little or no response. Using American Society for Therapeutic Radiology and Oncology criteria 3 of 10 responders had relapse after an average of 9 months. The remaining 7 patients remained biochemically free of disease at last followup. CONCLUSIONS: ProstaScint imaging is capable of detecting recurrent prostate cancer at low PSA levels. However, only 7 of 15 men (46.7%) with ProstaScint uptake isolated to the prostatic fossa showed a durable response to salvage radiation therapy. Based on these findings patients might be better treated based on the rate of increase in PSA rather than on routine scanning with this test.

Is the efficacy of hormonal therapy affected by lymph node status? data from the bicalutamide (Casodex) Early Prostate Cancer program.

OBJECTIVES: To report an exploratory subgroup analysis assessing the extent to which the overall benefit found in the Early Prostate Cancer program is dependent on lymph node status at randomization. The program is ongoing, and the overall survival data are immature. The first combined analysis of the bicalutamide (Casodex) Early Prostate Cancer program at 3 years' median follow-up showed that bicalutamide, 150 mg once daily, plus standard care (radical prostatectomy, radiotherapy, or watchful waiting), significantly reduced the risk of objective progression and prostate-specific antigen (PSA) doubling in patients with localized/locally advanced prostate cancer. METHODS: Men (n = 8113) with localized/locally advanced disease received bicalutamide 150 mg or placebo once daily, plus standard care. The time to event data (objective progression, PSA doubling) was analyzed by lymph node status at randomization. RESULTS: Compared with standard care alone, bicalutamide significantly reduced the risk of objective progression, irrespective of lymph node status, with the most pronounced reduction in patients with N+ (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.15 to 0.56) compared with those with N0 (HR 0.59; 95% CI 0.48 to 0.73) and Nx (HR 0.60; 95% CI 0.50 to 0.72) disease. The largest decrease in risk of PSA doubling with bicalutamide was observed in N+ disease (HR 0.16; 95% CI 0.09 to 0.29), with significantly reduced risks seen in N0 (HR 0.45; 95% CI 0.40 to 0.51) and Nx (HR 0.38; 95% CI 0.33 to 0.44) disease. CONCLUSIONS: The greatest reduction in the risk of objective progression and PSA doubling with bicalutamide was seen in patients with N+ disease. However, bicalutamide also provided a statistically significant benefit in those with N0 and Nx disease.

An evaluation of intermediate-dose ketoconazole in hormone refractory prostate cancer.

OBJECTIVES: The management of hormone refractory prostate cancer remains controversial. Among the options, second-line hormonal therapy is commonly used. We investigated the efficacy of ketoconazole, an inhibitor of testicular and adrenal androgen biosynthesis, for treating patients with advanced hormone refractory prostate cancer. METHODS: The study comprised 38 patients with progressive disease despite combined androgen blockade. Treatment consisted of intermediate-dose ketoconazole (300mg three times daily) and replacement hydrocortisone. Patients were monitored clinically and with serial psa measurements every 3 months. the principal endpoint was psa response. RESULTS: Of the 38 patients, 21 (55.3%) showed a decrease in PSA >50% (95% confidence interval 38.3%-71.4%) with a median duration of 6 months (range 3-48 months). A PSA reduction >50% was seen in 21 of 34 patients (61.8%) with established metastases. Thirteen patients (34.2%), all of whom had metastases, exhibited a PSA decrease >80% (95% confidence interval 19.6%-51.4%) with a median duration of 9 months (range 3-48 months). Age, PSA at diagnosis, Gleason score and bone scan result were not significantly associated with response to ketoconazole treatment in univariate or multivariate analyses. For the entire study group, the median time to progression was 5 months (range 0-27 months) and the median survival was 12 months (range 3-48 months). Overall, 12 patients (31.6%) reported toxicity related to intermediate-dose ketoconazole but only 6 patients (15.8%) discontinued therapy due to intolerable side effects. CONCLUSION: It is apparent from this study that a reasonable percentage of patients failing standard hormonal therapy respond favourably to intermediate-dose ketoconazole and that toxicity is mild. In the absence of studies demonstrating better survival with chemotherapy, we believe that a trial of ketoconazole should be considered when progression occurs on hormone therapy.

A critical review of maximal androgen blockade for advanced prostate cancer.

For over 60 years, the primary treatment for metastatic prostate cancer has been androgen ablation. Medical or surgical castration eliminates most, but not all androgen production, with a small contribution still coming from the adrenal gland. When castration fails, secondary adrenalectomy can provide some palliative benefit. However, the development of oral antiandrogens has offered an opportunity to simultaneously interfere with androgen produced in the testes and adrenal gland. Combined androgen blockade (CAB) has been investigated extensively with conflicting results. Based on a critical review of these studies, CAB still appears to offer the longest duration of survival and should continue to be offered as an option to men with metastatic disease.