Upper tract urothelial carcinoma topical issue 2016: treatment of metastatic cancer.

PURPOSE: To review the management of metastatic upper tract urothelial carcinoma (UTUC) including recent advances in targeted and immune therapies as an update to the 2014 joint international consultation on UTUC, co-sponsored by the Société Internationale d'Urologie and International Consultation on Urological Diseases. METHODS: A PubMed database search was performed between January 2013 and May 2016 related to the treatment of metastatic UTUC, and 54 studies were selected for inclusion. RESULTS: The management of patients with metastatic UTUC is primarily an extrapolation from evidence guiding the management of metastatic urothelial carcinoma of the bladder. The first-line therapy for metastatic UTUC is platinum-based combination chemotherapy. Standard second-line therapies are limited and ineffective. Patients with UTUC who progress following platinum-based chemotherapy are encouraged to participate in clinical trials. Recent advances in genomic profiling present exciting opportunities to guide the use of targeted therapy. Immunotherapy with checkpoint inhibitors has demonstrated extremely promising results. Retrospective studies provide support for post-chemotherapy surgery in appropriately selected patients. CONCLUSIONS: The management of metastatic UTUC requires a multi-disciplinary approach. New insights from genomic profiling using targeted therapies, novel immunotherapies, and surgery represent promising avenues for further therapeutic exploration.

Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: potential opportunities for immunotherapeutic approaches.

BACKGROUND: Despite aggressive multimodal therapy, locally advanced and/or metastatic penile squamous cell carcinoma (SqCC) is associated with significant morbidity and mortality, indicating a need for new therapeutic options. Given the emerging clinical utility of immunotherapeutics, we sought to assess the incidence and potential clinical significance of PD-L1 expression in penile SqCC. PATIENTS AND METHODS: Using an anti-PD-L1 primary antibody (clone 5H1), immunohistochemistry was carried out on whole tumor sections from 37 patients with penile SqCC treated at our institution between 2005 and 2013. PD-L1-positive tumors were defined as those with membranous staining in ≥5% of tumor cells. Association between PD-L1 expression and clinicopathologic parameters was examined using Fisher's exact test. Correlation between PD-L1 expression in primary tumors and matched metastases was assessed using the Spearman rank correlation coefficient (ρ). The difference in cancer-specific mortality between PD-L1-positive and -negative groups was examined using the log-rank test. RESULTS: Twenty-three (62.2%) of 37 primary tumors were positive for PD-L1 expression, and there was strong positive correlation of PD-L1 expression in primary and metastatic samples (ρ = 0.72; 0.032 < P < 0.036). Primary tumor PD-L1 expression was significantly associated with usual type histology (P = 0.040) and regional lymph node metastasis (P = 0.024), as well as decreased cancer-specific survival (P = 0.011). CONCLUSIONS: The majority of primary penile SqCC tumors express PD-L1, which is associated with high-risk clinicopathologic features and poor clinical outcome. These data provide a rational basis for further investigation of anti-PD-1 and anti-PD-L1 immunotherapeutics in patients with advanced penile SqCC.

Prognostic value of P53 nuclear accumulation and histopathologic features in T1 transitional cell carcinoma of the urinary bladder.

OBJECTIVES: To determine whether molecular and histopathologic tumor features can predict disease progression in Stage T1 transitional cell carcinoma of the bladder. METHODS: Tumor specimens from 43 patients were analyzed with respect to grade, presence of carcinoma in situ, invasion deep or superficial to the lamina propria's muscularis mucosa, p53 expression using DO-7 and PAb1801 antibodies, age, and sex. Flow cytometry was performed on 30 patients from whom there was adequate paraffin-embedded tissue to assess DNA ploidy. Seven patients underwent immediate cystectomy as primary treatment and 36 patients retained their bladders and were at risk of recurrence and progression. RESULTS: The median follow-up was 79 months. Disease recurred in 17 patients (47.2%) and progressed in 6 (16.7%). Only 3 patients (7.0%) died of bladder cancer. None of the parameters investigated was statistically significant in predicting recurrence, progression, or survival. Only carcinoma in situ approached statistical significance (P = 0.0593) as a predictor of progression. Early cystectomy did not have a significant effect on cancer-specific survival (P = 0.3603). The concordance rate between the two p53 antibodies was 88% (P <0.0001). CONCLUSIONS: Deep invasion of the lamina propria, p53 positive immunohistochemistry, high grade, and aneuploidy were not significant adverse prognostic factors for either disease progression or survival. Carcinoma in situ associated with Stage T1 transitional cell carcinoma may represent a biologically more aggressive cancer requiring early definitive therapy, but this hypothesis should be evaluated in prospective clinical studies.