There have been three main papers that assessed PDL-1 status in penile cancer, the John Hopkins group, Michigan group, and European group.1-3 While all small series, the results were also somewhat conflicting. The Michigan analysis identified 62% of 37 patients were positive for PDL-1, and it correlated to node status, unusual SCC histology, and cancer-specific morbidity. In the JHU results, 40% of 53 patients were positive for PDL-1, but it was not associated with HPV status or cancer-related morbidity. The European analysis of 210 tumors identified 45% PDL-1 positive patients. Stratified by diffuse or marginal PDL-1 positivity, the 36 patients with diffuse positivity had very poor CSS, while marginal PDL-1 positivity was protective. Of the 36 patients, 29 were HPV negative. As such, PDL-1 positivity in penile cancer is high, and while data is scarce, diffuse PDL-1 positivity may predict poor survival.
Genetic profiling of penile cancers is ongoing. From his review of multiple genomic studies utilizing small datasets, it would appear that the EGFR pathway appears to be important in penile cancer pathogenesis and may represent an actionable target. Cetuximab and panitumumab showed modest efficacy in palliative setting. A pan-HER inhibitor, dacomitinib, demonstrated encouraging results – 28 patients treated, 1 had complete response and 8 had partial response. Objective response rate is 32.1%.
He then went into a discussion of multimodal therapy, including chemotherapy and surgery. Neoadjuvant chemotherapy is a cisplatin-based chemotherapy with reported response rates up to 50%. In this patient population with very poor survival outcomes, any potential benefit is considered worthwhile. The standard regimen remains TIP chemotherapy.
The evidence is strong for NAC in patients with initially unresectable disease. However, for patients with resectable but high volume nodal disease is less certain. It has gained acceptance over the years and is now recommended for patients with cN2-3 disease (NCCN guidelines). In Europe, however, the paradigm remains surgery followed by adjuvant chemotherapy based on pathologic node status.
Chemoradiation, based on excellent evidence in head & neck squamous cell carcinoma, has been explored as well. It is also the standard of care for nodal control in vulvar cancer, which is similar to penile cancer. However, there are no randomized trials and no prospective data.
Ultimately, more data is needed for appropriate sequencing of multimodal therapy. Balancing morbidities such as lymphedema, infections, and chemotherapy toxicity in these patients with poor survival expectency is important.
The InPACT trial (ECOG-ACRIN EA8134) study aims to address some of these questions. Targeting an accrual of 400 patients, patients with clinical evidence of nodal involvement undergo two randomization steps. While there are multiple pathways for sequences available to the patients (available online at the clinicaltrials.org, NCT02305654), it does not include or assess adjuvant chemotherapy. US trial will be opening soon.
Presented By: Lance C. Pagliaro, MD, Mayo Clinic, Rochester, MN
Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto
1. Udager AM, Liu TY, Skala SL, Magers MJ, McDaniel AS, Spratt DE, Feng FY, Siddiqui J, Cao X, Fields KL, Morgan TM, Palapattu GS, Weizer AZ, Chinnaiyan AM, Alva A, Montgomery JS, Tomlins SA, Jiang H, Mehra R. Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: potential opportunities for immunotherapeutic approaches. Ann Oncol. 2016 Sep;27(9):1706-12. doi: 10.1093/annonc/mdw216. Epub 2016 May 23.
2. Cocks M, et al. Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort. Hum Pathol. 2017 Jan;59:55-61. doi: 10.1016/j.humpath.2016.09.003. Epub 2016 Sep 20.
3. Ottenhof SR, et al. Expression of Programmed Death Ligand 1 in Penile Cancer is of Prognostic Value and Associated with HPV Status. J Urol. 2017 Mar;197(3 Pt 1):690-697. doi: 10.1016/j.juro.2016.09.088. Epub 2016 Sep 30.
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA