Purpose of reviewThe purpose of this review is to look at recent advancements and treatment options of systemic therapies to treat penile squamous cell carcinoma (PSCC). PSCC is a rare cancer that remains with limited funding for research and systemic therapy development. This review aims to discuss the most recent advancements in systemic treatments and our understanding of PSCC. Recent findingsNeoadjuvant chemotherapy (NAC) and adjuvant therapy remain integral parts of treatment in locally advanced PSCC. New potential drug regimens are being studied to expand on the availability of first-line regimen options. There has been a large development in discoveries of cellular pathways and immune system targets as potential treatment options but these therapies as of today have limited trial evidence and currently have no support to be used in a clinical setting. SummaryPSCC is a rare genitourinary cancer with limited treatment options for patients with advanced disease that is refractory to chemotherapy. Although many new therapies targeting the immune system and cellular pathways are being developed for other studies, clinical and translational research for PSCC are still understudied and underfunded.
Penile Squamous Cell Carcinoma (PSCC) is associated with high-risk human papillomavirus (HR-HPV). The immunohistochemical (IHC) test for p16INK4a (p16) is highly correlated with HR-HPV expression in other SCCs. To investigate whether the expression of p16 IHC or HR-HPV is associated with survival in PSCC, we conducted a single institution analysis of 143 patients with a diagnosis of PSCC and, available tissue were tested for p16 IHC staining patterns, histological subtype, tumor grade, and lymphovascular invasion (LVI) by an experienced pathologist. HR-HPV status using the Cobas PCR Assay or the RNAScope high-risk HPV in situ hybridization kit were also assessed. Patient characteristics were summarized using descriptive statistics of clinico-pathologic variables. Kaplan–Meier was used to estimate median overall survival (OS), cancer specific survival (CSS) and correlated with HPV, p16, and other study variables. Patients with p16+ tumors had a significantly longer median CSS in comparison to the p16– group (p = 0.004), with respective 5-year CSS probability of 88% (95% CI; 0.84, 1) versus 58% (95% CI; 0.55, 0.76; p = 0.004). HPV status did not predict survival outcomes. Multivariable analysis with respect to OS and CSS, showed that p16+ status was associated with a lower risk of death (HR = 0.36, 95%CI; 0.20–0.67, p = 0.001), and improved CSS (HR = 0.20, 95% CI; 0.07–0.54, p = 0.002) after adjusting for covariates. In conclusion, tumor p16 status via IHC was an easy to perform independent prognostic factor for OS and CSS that correlates with HR-HPV expression.
using descriptive statistics of clinico-pathologic variables. Kaplan-Meier was used to estimate median overall survival (OS) and cancer specific survival (CSS). Log rank test, univariate and
5 Background: Penile Squamous Cell Carcinoma (PSCC) is associated with high risk human papillomavirus (HR-HPV) in about 50% of cases. The immunohistochemical test for p16INK4a (p16) is highly correlated with HR-HPV expression and used as prognostic marker for squamous cell carcinomas in various sites. The prognostic role of this marker in PSCC remains unclear. We studied whether the expression of HPV or p16INK4a is associated with survival in a large PSCC cohort. Methods: We conducted a single institution analysis of PSCC patients who received treatment between 1991-2017.Patients with a confirmed diagnosis of PSCC and available tissue were tested for HR-HPV status using the Cobas PCR assay. Histological subtype, tumor grade, LVI and p16 staining patterns were confirmed by an experienced pathologist. Patient characteristics were summarized using descriptive statistics of clinico-pathologic variables. Kaplan-Meier was used to estimate median overall survival (OS) and cancer specific survival (CSS). Log rank test, univariate and multivariate Cox models were applied to identify the prognostic factors for survival. Results: We identified 147 patients with PSCC, with available tissue for testing. The median follow-up was 5.2 years (95% CI; 4.48, 6.68y). Patients with p16(+) tumors showed a significantly longer median OS and CSS in comparison to the p16(–) group (p=0.038 and p=0.012), with respective 5 year OS probability of 73% (95% CI; 0.74, 0.98) in comparison to 56% (95% CI; 0.46, 0.67) and 5 year CSS probability of 89% (95% CI; 0.7, 1) in comparison to 64% (95% CI; 0.54, 0.75). In contrast, HPV status by PCR did not predict survival outcomes, with 5 year CSS probability for HPV(+) of 75% (95% CI; 0.61, 0.91) compared to 65% (95% CI; 0.55, 0.78) for HPV(–) patients. Multivariable analysis to evaluate the association with CSS, showed that p16(+) along with lymph node status was associated with lower risk of death (HR=0.28, 95%CI; 0.09-0.8, p=0.002), and OS (HR=0.49, 95%CI; 0.19-1.24, p=0.13) after adjusting for the covariates. Conclusions: Tumor p16 status was an independent prognostic factor for CSS in our PSCC cohort providing unique information above that of lymph node status alone.
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