Gleason 6 Prostate Cancer: Translating Biology into Population Health.

PURPOSE: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. MATERIALS AND METHODS: Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. RESULTS: The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. CONCLUSIONS: The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

Primary genitourinary melanoma: Epidemiology and disease-specific survival in a large population-based cohort.

BACKGROUND: Primary genitourinary (GU) melanoma is a rare disease, which is poorly characterized. OBJECTIVE: To examine clinical characteristics and survival outcomes of primary GU melanoma among men and women. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study using the Surveillance, Epidemiology, and End Results database (1973-2010) was used to identify primary GU melanoma cases by tumor site and histology codes. We examined associations of GU melanoma with demographic, clinical, and pathologic characteristics, as well as disease-specific survival (DSS). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: DSS was calculated using the Kaplan-Meier method. Cox-proportional hazard models were used to calculate hazard ratios and 95% CI for factors associated with worse DSS. RESULTS AND LIMITATIONS: A total of 1,586 histologically confirmed cases of primary GU melanoma were identified with a median age of 66.1 years (IQR: 55-80). Incidence of primary GU melanoma was 0.2cases/million among men and 1.80cases/million among women. Overall, 60.1% of patients had localized disease at presentation and 90.5% of patients had cancer-directed surgery. Patients with urothelial melanoma had the worst 5- and 10-year DSS (39% and 29%, respectively). Women with vulvar/vaginal melanoma had worse 5- and 10-year DSS compared to men with penile/scrotal melanoma. In multivariate analysis, decreased survival was associated with increasing age, distant stage, and lymph node involvement. Results are limited by the lack of standardized staging for primary GU melanoma and the retrospective design of our study. CONCLUSIONS: Patients with primary GU melanoma present with advanced stage and have a poor prognosis. Women have worse DSS compared to men. DSS is negatively associated with advanced age at diagnosis, higher stage, and lymph node involvement. PATIENT SUMMARY: Clinicians and patients must be aware of the poor disease-specific outcomes associated with primary GU melanoma. Most importantly, women fare worse than men and mucosal melanomas have worse outcomes compared to cutaneous melanomas.

Quality of Life in Long-term Survivors of Muscle-Invasive Bladder Cancer.

PURPOSE: Health-related quality of life (QOL) has not been well-studied in survivors of muscle-invasive bladder cancer (MIBC). The present study compared long-term QOL in MIBC patients treated with radical cystectomy (RC) versus bladder-sparing trimodality therapy (TMT). METHODS AND MATERIALS: This cross-sectional bi-institutional study identified 226 patients with nonmetastatic cT2-cT4 MIBC, diagnosed in 1990 to 2011, who were eligible for RC and were disease free for ≥2 years. Six validated QOL instruments were administered: EuroQOL EQ-5D, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire and EORTC MIBC module, Expanded Prostate Cancer Index Composite bowel scale, Cancer Treatment and Perception Scale, and Impact of Cancer, version 2. Multivariable analyses of the mean QOL scores were conducted using propensity score matching. RESULTS: The response rate was 77% (n=173). The median follow-up period was 5.6 years. Of the 173 patients, 64 received TMT and 109, RC. The median interval from diagnosis to questionnaire completion was 9 years after TMT and 7 years after RC (P=.009). No significant differences were found in age, gender, comorbidities, tobacco history, performance status, or tumor stage. On multivariable analysis, patients who received TMT had better general QOL by 9.7 points of 100 compared with those who had received RC (P=.001) and higher physical, role, social, emotional, and cognitive functioning by 6.6 to 9.9 points (P≤.04). TMT was associated with better bowel function by 4.5 points (P=.02) and fewer bowel symptoms by 2.7 to 7.1 points (P≤.05). The urinary symptom scores were similar. TMT was associated with better sexual function by 8.7 to 32.1 points (P≤.02) and body image by 14.8 points (P<.001). The patients who underwent TMT reported greater informed decision-making scores by 13.6 points (P=.01) and less concern about the negative effect of cancer by 6.8 points (P=.006). The study limitations included missing baseline QOL data and different follow-up times. CONCLUSIONS: Both TMT and RC result in good long-term QOL outcomes in MIBC survivors, supporting TMT as a good alternative to RC for selected patients. Whether TMT leads to superior QOL requires prospective validation.

Robotic-assisted Radical Nephrectomy With Retrohepatic Vena Caval Tumor Thrombectomy (Level III) Combined With Extended Retroperitoneal Lymph Node Dissection.

OBJECTIVE: To describe a case of robotic-assisted radical nephrectomy (RARN) with level III retrohepatic vena caval tumor thrombectomy (11 cm) and extended retroperitoneal lymph node dissection (RPLND) for renal cell carcinoma (RCC). MATERIALS AND METHODS: A 52-year-old woman with a large right renal mass, 11-cm (level III) inferior vena cava (IVC) thrombus, with a negative metastatic workup presented to our clinic and was consented to undergo RARN. Intraoperative ultrasound confirmed the presence of tumor thrombus. After the division of the renal artery, control of the vena cava above and below the tumor thrombus as well as contralateral renal vein was obtained. A cavotomy was performed, the thrombus was removed, and the cavotomy was repaired. Additionally, an extended RPLND was performed with robotic assistance. RESULTS: Total operative time was 6 hours and 6 minutes. Estimated blood loss was 1200 cc. The final pathology demonstrated an 8.5-cm, Fuhrman grade 3, clear cell RCC with sarcomatoid features and negative surgical margins. All 44 lymph nodes removed (hilar, paracaval, precaval, retrocaval, interaortocaval, and preaortic) were negative. Final staging was pT3b, N0, M0. The patient was discharged to home 36 hours postoperatively and experienced no perioperative or postoperative complications. CONCLUSION: RARN with retrohepatic (level III) vena caval tumor thrombectomy and extended RPLND is technically feasible and has potential benefits. Robotic assistance may allow for improved intracorporal repair of the IVC and shortened recovery time, while maintaining oncologic principles.

Prostato-symphyseal fistula after photoselective vaporization of the prostate: case series and literature review of a rare complication.

OBJECTIVE: To report our experience with the management of prostato-symphyseal fistula (PSF) after photoselective vaporization (PVP) or transurethral resection of the prostate (TURP) and review cases of this complication in published reports. MATERIALS AND METHODS: We report the management of 3 patients with PSF after PVP at our institution. A total of 5 published cases of PSF after PVP or TURP were identified from the National Library of Medicine MEDLINE database. A total of 8 patients were reviewed. RESULTS: Overall, the mean age was 71 years (range, 50-83 years), and average follow-up was 4.3 months (range, 1-7 months). Mean prostate volume was 32 mL (range, 16-38 mL). Five patients developed PSF after PVP and 3 patients after TURP. The most common postoperative symptoms included difficulty ambulating (100%) and pelvic, groin, and/or lower abdominal pain (85%). Associated diagnoses included osteitis pubis (38%) and urinoma (50%). Infectious complications were urinary tract infection (25%), osteomyelitis (38%), and infected urinoma (38%). Average time to diagnosis of PSF was 3.5 months (range, 0.5-11 months). Operative intervention was necessary in 75% of patients. CONCLUSION: This is the first reported case series on the management of PSF after PVP or TURP. This complication can be difficult to diagnose, manage, and may cause significant patient morbidity. Management requires a multidisciplinary approach. Patients commonly present with non-urologic symptoms leading to a delay in diagnosis. Further studies are needed to assess the incidence and optimal management of this complication.

Basal cell carcinoma of the prostate: a case report.

A 69-year-old man presented with gross hematuria and irritative urinary symptoms. He underwent transurethral resection of his prostate. The prostate chips revealed 70% poorly differentiated carcinoma with neuroendocrine features, initially read as small cell carcinoma, later as basal cell carcinoma. PSA at this time was 0.3. He received 4 cycles of etoposide and cisplatin. After which, rebiopsy of the prostate showed tumor consistent with poorly differentiated basal cell carcinoma. Given progression on chemotherapy, decision was made to proceed with radical prostatectomy. Metastatic workup was negative. Gross extraprostatic invasion was noted but lymph nodes were free of metastatic disease.

Effect of anti-estrogens on the androgen receptor activity and cell proliferation in prostate cancer cells.

Although some anti-estrogens have been reported to inhibit the proliferation of prostate cancer cells, few studies on the mechanism by which they suppress the growth of prostate cancer have been reported. We investigated, for the first time, whether anti-estrogens modulate the transactivation activity of the androgen receptor (AR) in prostate cancer cells. In DU-145 cells transfected with AR, the transactivation activity of AR was inhibited by tamoxifen and toremifene, even in the presence of 10 nM of DHT. On the other hand, in LNCaP cells having an endogenous AR mutation at codon 877, the activity of AR was suppressed by faslodex in the presence of 10 nM DHT, whereas it was not inhibited by tamoxifen nor toremifene. In PC-3 cells, both the cell growth and the AR activity were remarkably inhibited by tamoxifen at 50 microM. Faslodex and toremifene inhibited AR activity to some extent, but they seemed to function as agonists at higher concentrations. In PC-3 cells, the inhibition of cell growth by flutamide, faslodex and toremifene was much less than their suppression of AR activity. We also demonstrated that a synthetic estrogen diethylstilbestrol and progesterone-related drugs such as chlormadinone acetate and allylestrenol dose-dependently inhibited the activity of AR in DU-145 and PC-3 cells. These results highlight the anti-androgenic aspect of anti-estrogens and estrogens in regard to the AR-mediated transcription of the relevant genes in prostate cancer.