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-L1positive 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.

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Objective To determine if magnetic resonance imaging/ultrasound (MRI/US) fusion biopsy facilitates longitudinal re-sampling of the same clonal focus of prostate cancer (PCa) and to determine if high-grade cancers can evolve from low-grade clones. Materials and Methods All men on AS who underwent tracking MRI/US fusion biopsy of Gleason 6 PCa, on at least two distinct occasions, between 2012 and 2014 were enrolled. MRI/US fusion was used to track and re-sample specific cancer foci. Immunohistochemistry (IHC) for ERG and targeted RNA/DNA next generation sequencing (NGS) were performed on formalin-fixed paraffin-embedded (FFPE) prostate biopsy specimens to assess clonality. Results Thirty-one men with median age and PSA of 65 years and 4.6 ng/mL, respectively, were analyzed. The median sampling interval was 12 months (range 5 - 35). Of the 26 evaluable men, ERG IHC concordance was found between initial and repeat biopsies in 25 (96%), indicating re-sampling of the same clonal focus over time. Targeted NGS supported ERG IHC results and identified unique and shared driving mutations, such as IDH1 and SPOP, in paired specimens. Of the 9 (34.6%) men who were found to have Gleason ≥7 on repeat biopsy, all displayed temporal ERG concordance. Prioritized genetic alterations were detected in 50% (13/26) of paired samples. Oncogenic mutations were detected in 22% (2/9) of Gleason 6 cancers prior to progression and 44% (4/9) of Gleason ≥7 cancers when progression occurred. Conclusions Precise tracking of PCa foci via MRI/US fusion biopsy allowed subsequent re-sampling of the same clonal focus of cancer over time. Further research is needed to clarify the grade progression potential of Gleason 6 PCa.