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.

Nivolumab in patients with unresectable locally advanced or metastatic urothelial carcinoma: CheckMate 275 2-year global and Japanese patient population analyses.

BACKGROUND: Nivolumab has demonstrated antitumor activity and manageable safety in the single-arm, phase II CheckMate 275 study in patients with unresectable locally advanced or metastatic platinum-resistant urothelial carcinoma. We report updated results of the global population and a subanalysis of Japanese patients from this study. METHODS: Patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) confirmed by blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival (PFS) by BIRC and overall survival (OS). Safety was also reported. The minimum follow-up was 21 months. RESULTS: Overall, 270 patients were treated with nivolumab globally; 23 patients were Japanese. In the global and Japanese populations, respectively, ORR per BIRC was 20.4% and 21.7%; median PFS was 1.9 (95% confidence interval [CI] 1.9-2.3) and 3.8 months (95% CI 1.9-7.2); and median OS was 8.6 (95% CI 6.1-11.3) and 21.0 months (95% CI 7.2-not reached). The most common any grade treatment-related adverse events were fatigue (18.1%) and diarrhea (12.2%) in the global population; the most common in the Japanese population were diarrhea (26.1%) and pyrexia (13.0%). Grade 3 or 4 treatment-related adverse events occurred in 61 (22.6%) and seven (30.4%) of the global and Japanese patients, respectively. CONCLUSIONS: Nivolumab continues to show antitumor activity and survival in the global population of CheckMate 275. Meaningful clinical benefit was also observed in Japanese patients. No new safety signals were identified.

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.

Nivolumab in Patients with Advanced Platinum-resistant Urothelial Carcinoma: Efficacy, Safety, and Biomarker Analyses with Extended Follow-up from CheckMate 275.

PURPOSE: We report efficacy and safety with extended follow-up, and exploratory biomarker analyses from the phase II CheckMate 275 trial to identify biomarkers of response to nivolumab in platinum-resistant metastatic or unresectable urothelial carcinoma (mUC). PATIENTS AND METHODS: Patients received nivolumab 3 mg/kg once every 2 weeks until disease progression, unacceptable toxicity, or other protocol-defined reasons. The primary endpoint was objective response rate (ORR) per blinded independent review committee (BIRC; using RECIST v1.1) in all treated patients and by tumor PD-L1 expression. Key secondary endpoints were progression-free survival (PFS) per BIRC using RECIST v1.1 and overall survival (OS) in all patients and by PD-L1 expression. Exploratory endpoints included safety and biomarker analyses of tumor mutational burden (TMB), PD-L1, and previously identified mutational signatures. RESULTS: Of 270 treated patients, 139 had evaluable TMB. With 33.7 months' minimum follow-up, ORR per BIRC, median PFS, and median OS [95% confidence interval (CI)] in all treated patients were 20.7% (16.1-26.1), 1.9 months (1.9-2.3), and 8.6 months (6.1-11.3), respectively. No new safety signals were identified. Higher TMB was associated (P < 0.05) with improved ORR [OR (95% CI): 2.13 (1.26-3.60)], PFS [HR: 0.75 (0.61-0.92)], and OS [HR: 0.73 (0.58-0.91)]. TMB combined with PD-L1 better predicted ORR, PFS, and OS than PD-L1 alone. Higher mutational signature 2 score was associated with better OS but did not improve the predictive value of TMB. CONCLUSIONS: These results support the durable antitumor activity of nivolumab and suggest that TMB may enrich for better response in mUC. Future studies of TMB/PD-L1 as biomarkers for response to nivolumab in randomized trials are warranted.See related commentary by Swami et al., p. 5059.

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.

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.

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.

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%.

Serum prostate-specific antigen and survival after external beam radiotherapy for carcinoma of the prostate.

OBJECTIVES: To evaluate the significance of pretreatment prostate-specific antigen (pPSA) levels as a predictor of overall survival simultaneously with previously established prognostic factors. The pPSA level is a major predictor of treatment failure after radiotherapy and surgery, but to date has not been shown to predict survival. METHODS: This analysis was based on data from 927 patients with clinically localized prostate cancer treated with radiotherapy alone between 1987 and 1998. These patients were stratified into four prognostic risk groups, and multivariate analysis was used to determine the independent impact of pPSA level on PSA failure, progression-free survival (death from any cause after PSA failure), and overall survival (death from any cause). RESULTS: In a multivariate analysis simultaneously considering the prognostic risk group, a pPSA level greater than or equal to 20 ng/mL was associated with a higher risk of PSA failure and worse progression-free and overall survival. CONCLUSIONS: The pPSA level is an independent predictor of survival in patients initially treated with radiotherapy alone.

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.

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.

Neoadjuvant strategies for prostate cancer prior to radical prostatectomy.

Although definitive therapy with either radical prostatectomy or radiation therapy can be effective, the optimal treatment for prostatic adenocarcinoma remains controversial. Patients may be at significant risk for primary treatment failure even with apparent clinically localized disease. Thus, there has been increased interest in initial multimodal therapy in order to maximize the potential for cure. Neoadjuvant hormonal therapy prior to radical prostatectomy has been used for several decades and a large body of literature discusses its use; nevertheless, the current data suggest that it only decreases rates of positive surgical margins without improving prostate-specific antigen (PSA)-free or disease-free survival. Novel neoadjuvant hormonal and chemotherapeutic regimens are under investigation and may improve outcomes for patients undergoing radical prostatectomy.

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.

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.

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.

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.

How well does the Partin nomogram predict pathological stage after radical prostatectomy in a community based population? Results of the cancer of the prostate strategic urological research endeavor.

PURPOSE: The Partin nomogram uses preoperative Gleason grade, serum prostate specific antigen and clinical stage to predict pathological outcome after radical prostatectomy. It was developed and validated in a select population of patients at 3 academic institutions. Although the nomogram is widely used, it has yet to be validated in a community based population. We assessed the performance of the nomogram in the Cancer of the Prostate Strategic Urological Research Endeavor, a nationwide, community based observational disease registry of men with prostate cancer. MATERIALS AND METHODS: Included in the cohort were 1,162 men in Cancer of the Prostate Strategic Urological Research Endeavor who underwent radical prostatectomy. Using various probability thresholds the nomogram was used to predict outcomes in each patient. Using different probability thresholds receiver operating characteristics curves were then used to assess test performance. RESULTS: Of the men 860 (74%) had organ confined disease, 179 (15%) had established capsular penetration, 95 (8%) had seminal vesicle involvement and 37 (3%) had lymph node involvement. Calculated receiver operating characteristics curve area was 0.684 for predicting organ confined disease, 0.614 for predicting capsular penetration, 0.726 for predicting seminal vesicle involvement and 0.766 for predicting lymph node involvement. These values were lower than in previously published reports. CONCLUSIONS: While the Partin nomogram performs adequately in a community based cohort of men who undergo radical prostatectomy for localized prostate cancer, it does not attain the success demonstrated in previous studies in select academic cohorts. This result was likely due to differences in the distribution of pathological outcomes in the community based cohort, in which more men had organ confined disease.

Utility of intraoperative frozen section analysis of surgical margins in region of neurovascular bundles at radical prostatectomy.

OBJECTIVES: To report our experience with intraoperative frozen section (IFS) analysis in patients who are potential candidates for nerve-sparing surgery. Potency can be maintained in select patients who undergo radical prostatectomy using a nerve-sparing approach. However, extracapsular disease extension in the area of the neurovascular bundles may compromise adequate surgical margins in some patients undergoing such surgery. METHODS: We reviewed the pathologic results from 101 patients who underwent either unilateral or bilateral nerve-sparing radical prostatectomy in whom IFS analysis was performed. The clinical disease stage was T1 in 20 patients and T2 in 81 patients. The mean serum prostate-specific antigen level before surgery was 7.2 ng/mL. Of the 101 patients, 62, 28, and 11 had a biopsy Gleason score of 2 to 6, 7, and 8 to 10, respectively. IFS analysis was performed on the surgical margin thought to be at risk of tumor involvement as determined by the results of systematic prostate biopsy, transrectal ultrasonography, or intraoperative inspection. If the frozen section was positive, additional tissue, including the neurovascular bundle, was subsequently removed to establish clear surgical margins. IFS results were compared with those on the final, permanent tissue section, as well as with the status of the additionally resected tissue. RESULTS: The IFS results were identical to those obtained on the final, permanent section in 92 (91%) of the 101 cases. The IFS results showed positive margins in 15 (15%) of 101 patients. Of these cases, 11 demonstrated positive margins on the final permanent sections. Of the 86 patients with negative frozen section diagnosis, 5 had positive surgical margins on permanent sections at the site of the IFS. The positive and negative predictive value for the IFS technique was 73% and 94%, respectively. Of the 15 patients with positive IFS, 12 (80%) had no evidence of tumor in the additionally resected tissue. Prostate-specific antigen recurrence was noted in 7% of the study population. The risk of recurrence in patients with either positive or negative IFS findings was similar. CONCLUSIONS: IFS at the time of radical prostatectomy can reliably predict the final surgical margin status in most carefully selected high-risk patients when there are concerns about the margin status.

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.