Role of Indoleamine-2,3-Dioxygenase Inhibitors in Salvage Therapy for Non-Muscle Invasive Bladder Cancer.

Due to significant risks of cancer recurrence and progression, and limited options after intravesical Bacillus Calmette Guerin (BCG) therapy, there is a critical unmet need to identify novel treatments for those patients with BCG-unresponsive bladder cancer. There is active investigation of immunotherapies which provide both biologic and clinical rationales for indoleamine-2,3- dioxygenase inhibitors in salvage therapy for non-muscle invasive bladder cancer.

Emerging Immunotherapy Options for bacillus Calmette-Guérin Unresponsive Nonmuscle Invasive Bladder Cancer.

PURPOSE: Due to the high rate of recurrence and progression in patients with high risk nonmuscle invasive bladder cancer, there is an important unmet need to identify new therapies. This is particularly true for patients with recurrence after optimal intravesical bacillus Calmette-Guérin therapy, who are classified as having bacillus Calmette-Guérin unresponsive disease. MATERIALS AND METHODS: The PubMed® database was searched for publications related to immunotherapy for the treatment of patients with nonmuscle invasive bladder cancer who have recurrent or progressive disease despite receiving intravesical bacillus Calmette-Guérin therapy. Relevant congress abstracts were identified through searches of individual congress websites. Relevant planned and ongoing studies were identified via ClinicalTrials.gov or associated web searches. RESULTS: We provide a summary of the currently available immunotherapy options for patients with bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer, and discuss planned and ongoing research of potential targeted agents and immunotherapy based combination regimens. CONCLUSIONS: There is a clear biological and clinical rationale for the continued evaluation of immune based therapies in the setting of bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer. Data from early phase trials with novel immunotherapies targeting multiple immune related pathways have emerged, which support additional studies to assess the benefits of immune checkpoint inhibitors and other immunotherapy based regimens for patients with bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer.

Comparison of extraperitoneal and intraperitoneal augmentation enterocystoplasty for neurogenic bladder in spinal cord injury patients.

OBJECTIVES: Augmentation enterocystoplasty is the standard treatment for patients with neurogenic bladder who have failed medical management. Our "extraperitoneal" approach involves a small peritoneotomy to obtain the segment of bowel for augmentation, and a standard "clam" enterocystoplasty. We compared operative and postoperative parameters and clinical outcomes of this technique with the standard intraperitoneal technique. METHODS: We retrospectively reviewed charts of 73 patients with neurogenic voiding dysfunction refractory to medical management who underwent augmentation enterocystoplasty alone or in conjunction with additional procedures. A total of 49 patients underwent extraperitoneal augmentation and 24 patients underwent intraperitoneal augmentation. Operative and postoperative parameters including time of surgery, estimated blood loss, need for blood transfusion, time for return of bowel function, and length of hospital stay were examined. Clinical outcomes including early and late postoperative complications, and continence status were also analyzed. RESULTS: Median follow-up was 2.5 years. Patients in the extraperitoneal group had significantly shorter operative time (3.9 vs. 5.6 h, P < 0.0001); shorter hospital stay (8.0 vs. 10.5 days, P = 0.009); and shorter time to return of bowel function (3.5 vs. 4.9 days, P = 0.0005). There was no significant difference in complication rates. Postoperative continence was equally improved in both groups. When only patients with no prior abdominal surgery were compared, the findings were analogous: shorter operative time, shorter length of stay, sooner return of bowel function, and no difference in complication rate. CONCLUSIONS: The extraperitoneal technique provides an equally effective method of bladder augmentation to the standard technique with easier early postoperative recovery.

Fine needle aspiration cytology of adult perineal rhabdomyosarcoma: a case report.

BACKGROUND: Adult perineal soft tissue sarcomas are rare. Fewer than 30 cases have been reported, and all were diagnosed after surgical resection by histologic examination. Below we report a case in which the diagnosis was established preoperatively by fine needle aspiration (FNA). CASE: A 27-year-old man presented with a firm, midline, perineal mass. Magnetic resonance imaging showed a 3-cm, enhancing mass that was considered neoplastic. FNA biopsy, followed by cytologic examination, revealed moderately cellular aspirates composed of discohesive, small, blue cells with scant cytoplasm, high nuclear/cytoplasmic ratios and pleomorphic nuclei with irregular nuclear contours; uniform, hyperchromatic chromatin; and occasional mitotic figures. Frequent naked nuclei and scattered cells with more abundant, dense cytoplasm and eccentric nuclei were also noted. The diagnosis of rhabdomyosarcoma was favored on FNA and was corroborated by immunohistochemical stains for desmin, myogenin and CD56. Upon surgical resection, the diagnosis of alveolar rhabdomyosarcoma was confirmed histologically and immunophenotypically. CONCLUSION: FNA is a useful tool in diagnosing soft tissue lessions of the perineum, including rare primary tumors, such as adult rhabdomyosarcoma. In this case, early identification avoided incisional biopsy and directed appropriate extirpative surgery and reconstruction considerations.

Treatment and outcome of invasive bladder cancer in patients after renal transplantation.

PURPOSE: Optimal management and clinical outcome of bladder cancer in renal transplant recipients are not well-defined. We analyzed single institution treatment strategies and outcomes of these patients. MATERIALS AND METHODS: We retrospectively reviewed the University of California, San Francisco transplant database which contains information on 6,288 renal transplants performed between 1964 and 2002. The United Network for Organ Sharing database and Israel Penn International Transplant Tumor Registry were also queried to characterize the global nature of bladder cancer in renal transplant recipients. RESULTS: The United Network for Organ Sharing database (1986 to 2001) contained information on 31 patients who were found to have bladder cancer (0.024% prevalence) and the Israel Penn International Transplant Tumor Registry (1967 to 2001) contained information on 135 patients representing 0.84% of all reported malignancies. We identified 7 renal transplant recipients with bladder cancer at our institution. Invasive transitional cell carcinoma developed in 5 patients at a median of 2.8 years after transplant. Three patients underwent uncomplicated radical cystectomy and preservation of the renal allograft. Overall survival at 48 months was 60%. CONCLUSIONS: Bladder cancer after renal transplantation is not common. For patients who present with invasive disease, traditional extirpative surgery should be considered. Moreover, the allograft is rarely the source of transitional cell carcinoma and can be preserved. In our experience the cancer and urinary outcomes compare favorably with nontransplant patient outcomes after treatment.

Impact of patient educational level on treatment for patients with prostate cancer: data from CaPSURE.

OBJECTIVES: To examine the effect of a patient's educational level on treatment selection for patients with newly diagnosed prostate cancer. A patient's educational level may impact a patient's understanding and perception of the risks and benefits of the treatment options for prostate cancer. METHODS: We examined 3484 patients in CaPSURE with prostate cancer between 1992 and 2001. Chi-square and multinomial logistic regression analyses were performed to determine the role of education level in primary treatment received relative to other pretreatment predictors (age, race, insurance status, prostate cancer risk, comorbidity). Prostate cancer risk stratification was determined by serum prostate-specific antigen level and tumor stage and grade. RESULTS: The mean patient age was 67.7 +/- 8.3 years, and the mean prostate-specific antigen level was 13.0 +/- 18.7 ng/mL. Of the 3484 patients, 16.7% had less than a high school education, 27.0% had completed high school or technical school, 19.5% had had some college, 18.0% had graduated from college, and 18.6% had had some graduate education. In bivariate analysis, the factors predictive of treatment selection were patient age, race, education, insurance status, risk group, and patient comorbidity (all P <0.001). In multinomial regression analysis, the factors predicting treatment received were age, race, cancer risk group, and comorbidity. For patients older than 75 years, those with a higher education level received more aggressive treatment (radiotherapy versus hormonal therapy) than did those with less education. CONCLUSIONS: Patient age, race, cancer risk group, comorbidity, and, for men older than 75 years, education level are the factors predictive of the primary treatment received by men with newly diagnosed prostate cancer.

Health related quality of life patterns in patients treated with interstitial prostate brachytherapy for localized prostate cancer--data from CaPSURE.

PURPOSE: We measured the impact brachytherapy monotherapy (BMT) has on general and disease specific health related quality of life (HRQOL) compared to patients treated with radical prostatectomy (RP). MATERIALS AND METHODS: We studied 419 men with newly diagnosed prostate cancer who enrolled in CaPSURE (Cancer of the Prostate Strategic Urological Research Endeavor) data base whose primary treatment was brachytherapy monotherapy (92) or radical prostatectomy (327). The validated RAND 36-Item Health Survey and the UCLA Prostate Cancer Index were used to measure HRQOL before treatment and at 6-month intervals during the first 2 years after treatment. RESULTS: Patients treated with BMT or RP did not differ greatly in general HRQOL after treatment. Both treatment groups showed early functional impairment in most general domains with scores returning to or approaching baseline in most domains 18 to 24 months after treatment. Patients treated with BMT had significantly higher urinary function scores at 0 to 6 months after treatment (84.5, SD 18.7) than patients treated with RP (63.3, SD 26.6). Urinary bother scores at 0 to 6 months after treatment were not significantly different between patients treated with BMT (67.7, SD 31.2) and those treated with RP (67.4, SD 29.1). Both treatment groups had decreases in sexual function that did not return to pretreatment levels. CONCLUSIONS: Overall BMT and RP are well tolerated procedures that cause mild changes in general HRQOL. Disease specific HRQOL patterns are different in patients treated with BMT or RP. Baseline and serial HRQOL measurements after treatment can provide valuable information regarding expected quality of life outcome after treatment for localized prostate cancer.

National practice patterns and time trends in androgen ablation for localized prostate cancer.

BACKGROUND: Recent reports have suggested that growing numbers of patients with localized prostate cancer are receiving androgen deprivation therapy as primary or neoadjuvant treatment, yet sparse clinical evidence supports the use of such treatment except among patients with high-risk or locally advanced disease receiving external beam radiotherapy. We describe national trends in the use of androgen deprivation therapy for localized disease. METHODS: CaPSURE is an observational database of 7195 patients with prostate cancer. This study included 3439 of these patients who were diagnosed since 1989, had clinical staging information available, and were treated with radical prostatectomy, radiation therapy, or primary androgen deprivation therapy (PADT). High-, intermediate-, and low-risk groups were defined by serum prostate-specific antigen level, Gleason score, and clinical tumor stage. Time trends in the use of PADT and neoadjuvant androgen deprivation therapy (NADT) were analyzed. All statistical tests were two-sided. RESULTS: Rates of PADT use rose sharply between 1989 and 2001, from 4.6% (95% confidence interval [CI] = 3.4% to 5.8%) to 14.2% (95% CI = 12.2% to 16.2%), from 8.9% (95% CI = 7.3% to 10.5%) to 19.7% (95% CI = 17.5% to 21.9%), and from 32.8% (95% CI = 29.9% to 35.7%) to 48.2% (95% CI = 45.1% to 51.3%) (all P<.001) in low-, intermediate-, and high-risk groups, respectively. NADT use also increased in association with radical prostatectomy (2.9% [95% CI = 2.1% to 3.7%] to 7.8% [95% CI = 6.5% to 9.1%] of patients, P =.003) and external beam radiotherapy (9.8% [95% CI = 7.5% to 12.1%] to 74.6% [95% CI = 70.8% to 78.4%], P<.001) across all risk levels combined. Rates of NADT use among patients treated with brachytherapy also increased but not statistically significantly (7.4% [95% CI = 3.5% to 11.3%] to 24.6% [95% CI = 18.2% to 31.0%], P =.100). CONCLUSIONS: Rates of both PADT and NADT are increasing across risk groups and treatment types. Future clinical trials must define more clearly the appropriate role of hormonal therapy in localized prostate cancer, and their results should shape updated practice guidelines.

Significance of high-grade prostatic intraepithelial neoplasia on prostate biopsy.

The early diagnosis of prostate cancer has been facilitated by the development of serum prostate-specific antigen (PSA) testing and evolution in transrectal ultrasound-guided biopsy of the prostate. Over a decade has passed since the initial recommendations for systematic sextant sampling of the prostate to increase the accuracy of cancer detection. Subsequently, variations in the number and location of biopsies have been proposed to maximize prostate cancer detection and obtain more complete information regarding tumor grade, tumor volume, and local stage. Although current biopsy strategies provide a wide sampling of the prostate gland, biopsy histology may not be conclusive for either the presence or absence of adenocarcinoma. High-grade prostatic intraepithelial neoplasia (HGPIN) is found in a significant fraction of patients undergoing transrectal prostate biopsies. In this article, we discuss the significance of high-grade prostatic intraepithelial neoplasia and other abnormal histology findings and current evidence addressing the presence of cancer and need for additional prostate biopsies.

How potent is potent? Evaluation of sexual function and bother in men who report potency after treatment for prostate cancer: data from CaPSURE.

OBJECTIVES: To characterize the association between potency and comprehensive sexual function. The accurate assessment of sexual function is critical for the evaluation of outcomes after treatment of prostate cancer. The assessments of potency typically used in this context, however, may be oversimplified. METHODS: CaPSURE is a large, observational database of men with prostate cancer. Participants complete health-related quality-of-life questionnaires, including the University of California, Los Angeles Prostate Cancer Index, every 6 months after treatment. A total of 5135 men completed at least one questionnaire and did not use medications for erectile function. The men were categorized as potent or impotent based on their ability to have erections and/or intercourse in the prior 4 weeks. Using the remaining questions on the Prostate Cancer Index, sexual function and bother scores were calculated for each group. RESULTS: Of the 5135 men, 27.4% were potent. The mean sexual function scores were 56 and 13 for potent and impotent men, respectively (P <0.0001). The corresponding mean bother scores were 62 and 36 (P <0.0001). The function scores ranged from 0 to 100 and 0 to 92 among potent and impotent men, respectively, and bother scores from 0 to 100 in both groups. Function was inversely associated with age in both groups, but bother did not change among potent men and ameliorated among impotent men. Individual Prostate Cancer Index questions correlated with potency to a variable extent. CONCLUSIONS: Although potent and impotent men have divergent sexual function and bother scores after treatment, the wide range of these scores in both groups denotes a complex picture of sexual function. The simple documentation of potency after treatment provides an insufficient measure of sexual health-related quality of life and should be supplemented with more comprehensive measures.

Quantitation of apoptotic activity following castration in human prostatic tissue in vivo.

BACKGROUND: Androgen deprivation induces apoptosis in the prostate. Representative data, quantitating apoptotic activity in human prostatic epithelium following androgen ablation, are lacking. METHODS: Human prostatic tissue was grafted beneath the renal capsule of intact male athymic mice and allowed to become established. The mice were castrated and specimens were harvested on post-castration day 0, 1, 2, 3, 4, 5, 7, 8, 9, 10, 14, 17, 18, and 21. Tissue was immediately fixed and apoptotic epithelial nuclei were identified. RESULTS: The percentage of terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) positive epithelial cells increased from a baseline of 0.026%, peaked on post-castration day 3 (1.54%), and returned to baseline by day 21. Mathematical analysis predicted that the observed apoptotic activity account for the loss of 87% of prostatic epithelial cells in 3 weeks. CONCLUSIONS: Post-castration apoptosis in human prostatic epithelium was low but was sufficient to account for the loss of nearly 90% of epithelial cells.

Predicting recurrence after radical prostatectomy for patients with high risk prostate cancer.

PURPOSE: Previous studies have shown that patients with clinical stage T2c-T3 prostate cancer, serum prostate specific antigen (PSA) at diagnosis greater than 20 ng./ml. or a biopsy Gleason score of 8 to 10 are at high risk for disease recurrence after radical prostatectomy. We determined the most important pretreatment predictors of disease recurrence in this high risk population. MATERIALS AND METHODS: We identified 547 patients with high risk prostate cancer who underwent radical prostatectomy at University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor data base, a longitudinal disease registry of patients with prostate cancer. High risk disease was defined as 1992 American Joint Committee on Cancer clinical stage T2c-T3 disease in 411 patients, serum PSA at diagnosis greater than 20 ng./ml. in 124 and/or biopsy Gleason score 8 to 10 in 114. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment more than 6 months after surgery. The Cox proportional hazards analysis was performed to determine significant independent predictors of disease recurrence. The likelihood of disease recurrence for clinically relevant patient groups was determined using the Kaplan-Meier method and compared using the log rank test. RESULTS: Median followup after surgery was 3.1 years. Disease recurred in 177 patients (32%). Multivariate analysis demonstrated that serum PSA at diagnosis, biopsy Gleason score, ethnicity and the percent of positive prostate biopsies were significant independent predictors of disease recurrence, while patient age and clinical tumor stage were not. Patients with a Gleason score 8 to 10 tumor and a serum PSA of 10 ng./ml. or less had a significantly higher likelihood of remaining disease-free 5 years after surgery than those with PSA greater than 10 ng./ml. (47% versus 19%, p <0.05). Patients with a serum PSA at diagnosis of greater than 20 ng./ml. and a Gleason score of less than 8 had a significantly higher likelihood of remaining disease-free 5 years after surgery than similar patients with a Gleason score of 8 or greater (45% versus 0%, p <0.05). CONCLUSIONS: PSA, Gleason score, ethnicity and the percent of positive prostate biopsies appear to be the most important pretreatment predictors of disease recurrence in men with high risk prostate cancer. Patients with high grade disease may continue to be appropriate candidates for local therapy if PSA is less than 10 ng./ml. at diagnosis or there are fewer than 66% positive prostate biopsies.

Cancer and Leukemia Group B (CALGB) 90203: a randomized phase 3 study of radical prostatectomy alone versus estramustine and docetaxel before radical prostatectomy for patients with high-risk localized disease.

The purpose of The Cancer and Leukemia Group B (CALGB) 90203 trial is to determine which of 2 treatment strategies is superior in treating men with high-risk, clinically localized adenocarcinoma of the prostate (stage T1 to T3a NX M0), defined as a predicted probability < or =60% of remaining free from disease recurrence for 5 years after surgery. Patients with a > or =10-year life expectancy will be randomized to either radical prostatectomy (RP) alone versus estramustine and docetaxel before RP. Participants will be excluded if they have received prior therapy for prostate cancer (except transurethral resection of the prostate) or are judged not to be appropriate candidates for RP. Eligible patients will be stratified according to their predicted probability of remaining free from disease recurrence at 5 years after surgery (0% to 20%, 21% to 40%, and 41% to 60%) and randomized. Neoadjuvant chemotherapy will be 6 cycles (1 cycle = 21 days) of estramustine (280 mg tid, days 1 to 5) and docetaxel (70 mg/m2 on day 2). Warfarin (2 mg/day orally) will be given for prophylaxis against deep venous thrombosis. Bilateral pelvic lymph node dissection and RP will be performed within 60 days of registration/randomization for men randomized to the surgery-alone arm. For men randomized to receive preoperative chemotherapy, the surgical procedure will be performed within 60 days of completion of chemotherapy. Patients will be monitored with history review, physical examination, and serum prostate-specific antigen (PSA) levels every 3 months for the first 3 years after surgery, every 6 months for the next 3 years, and annually thereafter. Biochemical disease recurrence will be defined as a serum PSA level >0.4 ng/mL on 2 consecutive occasions > or =3 months apart after RP. The time of biochemical failure is measured from the date of randomization to the time of the first PSA level <0.4 ng/mL that is confirmed on the second serial PSA. The primary study end point is to determine if early systemic treatment with neoadjuvant estramustine and docetaxel before RP in patients with high-risk prostate cancer will decrease 5-year recurrence rates when compared with RP alone. Secondary outcomes will include (1) the safety and tolerability of neoadjuvant estramustine and docetaxel before RP; (2) the impact of this neoadjuvant strategy on pathologic tumor stage, including lymph node and surgical margin status; (3) time to clinically apparent disease recurrence; and (4) overall survival. The impact of RP with and without neoadjuvant estramustine and docetaxel on the patient's quality of life from pretreatment through year 3 will be assessed. Frozen prostate tissue will be obtained from men undergoing prostatectomy who are enrolled in either the treatment or control arms of the trial. These samples will be analyzed for their RNA expression patterns in order to build outcome prediction models. Furthermore, using array-based methods of expression analysis, the sensitivity to chemotherapeutic agents and response to chemotherapy may likewise be predicted. The trial will enroll approximately 700 men during a 48-month period. Patients will be observed for 84 months after study closure. The power to detect a 36% decrease in 5-year recurrence rates is 90%.

Is ethnicity an independent predictor of prostate cancer recurrence after radical prostatectomy?

PURPOSE: Prostate cancer incidence and mortality are higher in black than in white American men. We determined whether ethnicity is an independent predictor of disease recurrence in men undergoing radical prostatectomy. MATERIALS AND METHODS: We studied 1,468 patients who underwent radical prostatectomy at the University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor database, a longitudinal disease registry of patients with prostate cancer. Preoperative characteristics, including age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage, biopsy Gleason score and percent positive prostate biopsies at diagnosis were determined in each patient. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment at least 6 months after surgery. Cox proportional hazards analysis was performed to determine independent predictors of time to disease recurrence. To control for pretreatment disease characteristics simultaneously patients were assigned to previously described risk groups based on clinical tumor stage, PSA at diagnosis and biopsy Gleason score. The likelihood of disease recurrence per risk group stratified according to ethnicity was determined using the Kaplan-Meier method and compared using the log rank test. Additional multivariate analysis was performed in the subset of patients enrolled in Cancer of the Prostate Strategic Urological Research Endeavor on whom education and income information was available. RESULTS: Disease recurred in 304 of the 1,468 patients (21%). Black ethnicity, serum PSA at diagnosis, biopsy Gleason score and percent positive prostate biopsies were independent predictors of recurrence on multivariate analysis. Black ethnicity remained an independent predictor of disease recurrence in the multivariate model after stratifying patients into risk groups (p = 0.0007). Ethnicity was most important in patients at high risk, in whom estimated 5-year disease-free survival was 65% and 28% in white and black men, respectively. Education, income and ethnicity correlated highly. When education and income were entered into the multivariate model, ethnicity was no longer an independent predictor of outcome after prostatectomy. CONCLUSIONS: Ethnicity appears to be an independent predictor of disease recurrence after adjusting for pretreatment measures of disease extent in patients undergoing radical prostatectomy. It appears to be particularly important in those with high risk disease characteristics. However, black ethnicity, education and income are highly correlated variables, suggesting that sociodemographic factors may contribute to the poorer outcomes in black patients even after adjusting for differences in pretreatment disease characteristics.

Sociodemographic characteristics and health related quality of life in men attending prostate cancer support groups.

PURPOSE: Prostate cancer can be associated with anxiety, depression and fears of recurrence and side effects of treatment. Support groups may help meet the needs of patients with cancer by providing treatment information and emotional support. We describe men in prostate cancer support groups and compare them to a national registry. METHODS AND METHODS: Men attending prostate cancer support groups in the San Francisco Bay area completed a questionnaire including sociodemographic and clinical characteristics, health related quality of life items, satisfaction with treatment, relief of prostate cancer symptoms and bother from perceived side effects of treatment. Patients in support groups were compared to men enrolled in a national prostate cancer registry (Cancer of the Prostate Strategic Urological Research Endeavor). RESULTS: Men attending support groups had higher annual income and education levels, lower median serum prostate specific antigen and higher cancer grades than men in Cancer of the Prostate Strategic Urological Research Endeavor. Clinical stage was comparable for the 2 groups. Men in support groups were satisfied with treatment and alleviation from symptoms. Adjusting for ethnicity, marital status, age and type of treatment, sexual function scores were higher in men who attended support groups (p = 0.001). There was no statistically significant difference in bowel and urinary function between groups, although urinary function approached statistical significance at p = 0.05. Sexual and bowel bother scores indicated less bother for men in support groups (p < or = 0.025). CONCLUSIONS: Men enrolled in support groups have unique sociodemographic characteristics. Their health related quality of life appears to be better than that of other men with prostate cancer. Whether this is related to support group participation is not known. Additional studies are required to determine whether routine support group participation improves outcomes in men with prostate cancer.

Surgery for prostate cancer: rationale, technique and outcomes.

Prostate cancer is the most common non-cutaneous malignancy in men and poses a substantial risk to the life and health of patients. Treatment options for patients with prostate cancer are plentiful. Radical prostatectomy is one option that can be performed using several different surgical approaches. It can be performed with limited risk of complications and is likely to be curative in patients with organ-confined disease and those with limited extracapsular extension.

Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer.

Although once reserved for the management of metastatic prostate cancer, androgen deprivation therapy (ADT) is being used increasingly to treat lower stages of disease. We sought to assess patterns of ADT use in a contemporary cohort of men newly diagnosed with prostate cancer. Men with newly diagnosed prostate cancer who had > or =12 months of follow-up evaluation were identified in a national disease registry of patients with prostate cancer. The patterns of ADT use, both primary and secondary, were characterized and stratified by risk according to prostate-specific antigen levels, clinical stage, and Gleason score. In a cohort of 1485 men, 46% underwent ADT at some point during their treatment: 41% as primary therapy (either sole therapy or neoadjuvant therapy), and 5% as secondary therapy. In all, 50% of men receiving initial ADT had low- or intermediate-risk disease characteristics. Among patients treated with radical prostatectomy and radiation therapy, neoadjuvant ADT was administered in 20% and 48% of patients, respectively. Secondary hormonal manipulation was observed in 5% and 7% of patients treated initially with surgery or radiation, respectively. ADT is commonly used to treat men with prostate cancer. Much of the use of ADT is in men with low- and intermediate-risk disease characteristics. The appropriateness of such therapy requires further study, including its effect, not only on disease endpoints, but also on resource utilization and health-related quality of life.

Patterns of failure after primary local therapy for prostate cancer and rationale for secondary therapy.

The timing and type of treatment for patients with biochemical disease recurrence after local therapy for prostate cancer remains controversial. This is because of many unresolved issues surrounding the natural history of disease progression in such patients, including the limited ability of clinical measures to accurately define local versus distant disease recurrence. Clinicians generally rely on clinical tumor characteristics, such as tumor stage, grade, and prostate specific antigen (PSA) kinetics after local therapy, to distinguish local from distant recurrence. This determination is important, because patients with local recurrence may be candidates for a second, potentially curative treatment, whereas those with distant recurrence are generally treated with androgen deprivation therapy (ADT). Data from a national disease registry of patients with prostate cancer, the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), suggest that the use of secondary cancer treatment after local therapy for prostate cancer is common. For patients initially treated with radical prostatectomy, secondary treatment appears to be nearly equally divided between postoperative radiation and ADT, whereas >90% of patients receiving a secondary treatment after radiation are treated with ADT. Serum PSA at diagnosis, Gleason score, and type of initial treatment appear to be predictors of secondary treatment use in this setting. Patient age, lymph node status, and margin status appear to be predictors of secondary treatment with ADT or radiation for patients initially treated with radical prostatectomy.

A review of measurement of patient preferences for treatment outcomes after prostate cancer.

The diagnosis of early-stage prostate cancer cases creates dilemmas for many men diagnosed with the disease each year. Treatment interventions are all associated with significant treatment morbidity, including impotence and incontinence. The basic concept behind patient preferences, or utilities, is to ask patients to make judgments about the value of particular health outcomes. Several preference-based instruments are available, including the visual analog rating scale, the time trade-off utility assessment, and the standard gamble. These assessments result in scores or weights assigned to different health states. From the perspective of the patient with prostate cancer, the treatment that produces optimal outcomes will depend on the relative importance of several domains, which may include pain, urinary functioning, sexual functioning, and general physical health. Patients with similar diagnoses and overlapping clinical characteristics may have markedly different preferences for treatment outcomes.