Glen W. Barrisford

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 spermatic cord tumors: Disease characteristics, prognostic factors, and treatment outcomes

INTRODUCTION Experience with management of spermatic cord tumors (SCTs) is uncommon. We utilized a large population-based cancer registry to characterize the demographic, pathological, treatment characteristics, and outcomes of SCTs. MATERIAL AND METHODS The Surveillance, Epidemiology, and End Results database (1973-2007) was queried. RESULTS From the database, 362 patients were identified with SCT. The annual incidence of SCT was 0.3 cases per million and did not change over time. The most common histologic types were liposarcoma (46%), leiomyosarcoma (20%), histiocytoma (13%), and rhabdomyosarcoma (9%). The median age of diagnosis for rhabdomyosarcomas was (26.3 y), whereas for other SCTs, it was (64.7 y) (P<0.001). On multivariate analysis, a worse outcome was observed with undifferentiated tumor grade, distant disease, positive lymph nodes, and leiomyosarcoma or histiocytoma cell histology. CONCLUSION We describe the largest cohort of SCT studied to date. Liposarcoma was most common, while leiomyosarcoma and histiocytoma histologic subtypes were observed to be the most aggressive. Multivariate analysis revealed that tumor grade, stage, histologic type, and lymph node involvement were independently predictive of prognosis.

Testicular Cancer: What the Radiologist Needs to Know

OBJECTIVE The purpose of this article is to review current imaging techniques and evolving technologies that are being used for detection and management of testicular cancer. CONCLUSION The primary goal of cancer imaging is accurate disease characterization at diagnosis and through all stages of management. Knowledge of the disease and diagnostic performance characteristics of each technique is critical to identify the appropriate modality for staging disease and to monitor for treatment response and recurrence that may dictate further intervention.

Clinical features of leiomyosarcoma of the urinary bladder: Analysis of 183 cases

INTRODUCTION Experience with management of urinary bladder leiomyosarcoma (LMS) is rare. Therefore, to better elucidate the disease characteristics of urinary bladder LMS, we utilized a large population-based cancer registry to examine the epidemiology, natural history, pathological characteristics, prognostic factors, and treatment outcomes. MATERIAL AND METHODS The Surveillance, Epidemiology, and End Results database (1973-2010) was used to identify cases by tumor site and histology codes. The association between clinical and demographic characteristics and long-term survival was examined. RESULTS A total of 183 histologically confirmed cases were identified between 1973 and 2010. The annual age-adjusted incidence rate was 0.23 cases per 1,000,000 and did not significantly change over time. Median age of the patients was 65 years (interquartile range: 47-78 y). Of the patients with a known pathologic tumor stage (n = 164), 50% had a regional or distant disease. Overall, 63.2% of patients with known histologic grade (n = 106), had poorly differentiated or undifferentiated histology. Most patients (92.9%) received cancer-directed surgery (CDS), with 34.4% having radical or partial cystectomy. Only 7.7% of patients received radiation therapy in combination with surgery. The median disease-specific survival was 46 months. Five- and 10-year cancer-specific survival rates were 47%, and 35%, respectively. On multivariate analysis, a worse outcome was associated with an undifferentiated tumor grade, distant disease, and failure to undergo CDS. CONCLUSION This series represents the largest cohort of LMS of the urinary bladder studied to date. LMS commonly presented as high grade and advanced stage with a poor prognosis. Reduced disease-specific survival was associated with increasing age, undifferentiated tumor grade, distant disease, and failure to undergo CDS.

The role of lymphadenectomy in the management of renal cell carcinoma

Abstract The role of lymphadenectomy in the management of renal cell carcinoma has been established in staging but is less well defined as a therapeutic maneuver. Level one evidence suggests no survival benefit or increased complication rate with lymphadenectomy when performed concurrently with radical nephrectomy. However, several retrospective studies have identified a survival benefit when patients with increased risk of micrometastatic lymph node disease undergo lymphadenectomy. We perform a selective review of the literature and present the historical basis, risk assessment, use and development of nodal templates, and therapeutic benefits associated with the use of lymphadenectomy in the management of renal cell carcinoma.

Active surveillance for low-risk prostate cancer: Need for intervention and survival at 10 years.

INTRODUCTION To describe the need for treatment and cancer-specific and overall survival in a contemporary active surveillance (AS) cohort. PATIENTS AND METHODS Historical cohort study of men diagnosed with localized prostate cancer between 1997 and 2009 and managed with AS at a tertiary care center. Inclusion criteria were Gleason score ≤ 6 (Gleason score of 7 in select patients),≤ 3/12 cores positive, and prostate-specific antigen (PSA) level< 20 ng/ml. Survival analyses were conducted using the Kaplan-Meier method. RESULTS A total of 469 men with median age at diagnosis of 68.1 years (interquartile range [IQR]: 62.5-73.4) were followed up for a median of 4.8 years (IQR: 3.4-7.3). Median PSA level at diagnosis was 5.1 ng/ml (IQR: 4.0-6.9), with 94% of them having PSA level<10 ng/ml. Overall, 98.3% (461/469) of patients had a Gleason score of 6 and 1.7% (8/469) had a Gleason score of 3+4 = 7, and 94.0% (441/469) had T1c stage disease. Freedom from treatment was 77% at 5 years and 62% at 10 years. A total of 116 (24.7%) patients received treatment during the course of surveillance. Reasons for treatment included 44.8% (52/116) for pathologic reclassification, 30.2% (35/116) for PSA progression, 12.1% (14/116) for patient preference, 5.2% (6/116) for digital rectal examination progression, and 4.3% (5/116) for metastatic disease. Of the patients treated, 59 (50.1%) received radiation, 26 (22.4%) underwent surgery, 17 (14.7%) received brachytherapy, and 14 (12.1%) received androgen-deprivation therapy. Cancer-specific survival was 100% at 5 and 10 years. Overall survival was 95% at 5 years and 88% at 10 years. CONCLUSION In a contemporary cohort of men with low-risk prostate cancer, AS allowed avoidance of treatment most of them. Common reasons for change in management were Gleason upgrading and volume progression on prostate rebiopsy.

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.

Penis Transplantation: First Us Experience

Objective: We describe the first successful penis transplant in the United States in a patient with a history of subtotal penectomy for penile cancer. Background: Penis transplantation represents a new paradigm in restoring anatomic appearance, urine conduit, and sexual function after genitourinary tissue loss. To date, only 2 penis transplants have been performed worldwide. Methods: After institutional review board approval, extensive medical, surgical, and radiological evaluations of the patient were performed. His candidacy was reviewed by a multidisciplinary team of surgeons, physicians, psychiatrists, social workers, and nurse coordinators. After appropriate donor identification and recipient induction with antithymocyte globulin, allograft procurement and recipient preparation took place concurrently. Anastomoses of the urethra, corpora, cavernosal and dorsal arteries, dorsal vein, and dorsal nerves were performed, and also inclusion of a donor skin pedicle as the composite allograft. Maintenance immunosuppression consisted of mycophenolate mofetil, tacrolimus, and methylprednisolone. Results: Intraoperative, the allograft had excellent capillary refill and strong Doppler signals after revascularization. Operative reinterventions on postoperative days (PODs) 2 and 13 were required for hematoma evacuation and skin eschar debridement. At 3 weeks, no anastomotic leaks were detected on urethrogram, and the catheter was removed. Steroid resistant-rejection developed on POD 28 (Banff I), progressed by POD 32 (Banff III), and required a repeat course of methylprednisolone and antithymocyte globulin. At 7 months, the patient has recovered partial sensation of the penile shaft and has spontaneous penile tumescence. Our patient reports increased overall health satisfaction, dramatic improvement of self-image, and optimism for the future. Conclusions: We have shown that it is feasible to perform penile transplantation with excellent results. Furthermore, this experience demonstrates that penile transplantation can be successfully performed with conventional immunosuppression. We propose that our successful penile transplantation pilot experience represents a proof of concept for an evolution in reconstructive transplantation.

Role of imaging in testicular cancer: current and future practice.

The article provides a summary of the epidemiologic and clinical aspects of testicular malignancy. Current standard imaging and novel techniques are reviewed. Present data and clinical treatment trends have favored surveillance protocols over adjuvant radiation or chemotherapy for low-stage testicular malignancy. This has resulted in increasing numbers of imaging studies and the potential for increased long-term exposure risks. Understanding imaging associated risks as well as strategies to minimize these risks is of increasing importance. The development, validation and incorporation of alternative lower risk highly efficacious and cost-effective imaging techniques is essential.

Type 2 Diabetes in Relation to the Risk of Renal Cell Carcinoma Among Men and Women in Two Large Prospective Cohort Studies

OBJECTIVE We assessed whether type 2 diabetes is associated with renal cell carcinoma (RCC), independent of key potential confounders, in two large prospective cohorts with biennially updated covariate data. RESEARCH DESIGN AND METHODS A total of 117,570 women from the Nurses’ Health Study (NHS) and 48,866 men from the Health Professionals Follow-Up Study (HPFS) were followed from 1976 and 1986, respectively, through 2014. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs for associations between type 2 diabetes and pathology-confirmed RCC, overall and by stage, grade, and histologic subtype. RESULTS During 38 years of follow-up in the NHS, we confirmed 418 RCC case subjects, including 120 fatal cases. Over 28 years in the HPFS, we confirmed 302 RCC case subjects, including 87 fatal cases. Women with type 2 diabetes had a significantly increased risk of RCC compared with women without type 2 diabetes (multivariable HR 1.53; 95% CI 1.14–2.04), with some evidence that the association was stronger for ≤5 (HR 2.15; 95% CI 1.44–3.23) than >5 (HR 1.22; 95% CI 0.84–1.78) years’ duration of type 2 diabetes (Pdifference 0.03). Among men, type 2 diabetes was not associated with total RCC (HR 0.89; 95% CI 0.56–1.41) or with RCC defined by stage, grade, or subtype. Sample sizes for analyses by stage, grade, and subtype were limited. CONCLUSIONS We found that type 2 diabetes was independently associated with a greater risk of RCC in women but not in men.