ASCO GU 2018: Comparative Genomic Profiling of Refractory/Metastatic Penile And Non-penile Cutaneous Squamous Cell Carcinoma

San Francisco, CA (UroToday.com) Men with metastatic squamous cell carcinoma (SCC) of the penis who have failed first line chemotherapy have few systemic treatment options available to them. With the goal of determining if there are any potential targetable pathways in men with penile SCC, Dr. Joseph Jacob presented his data on the comparative genomic profiling of metastatic penile cancer and non-penile cutaneous squamous cell carcinoma.

Tissue samples from 446 patients with metastatic SCC (78 penile SCC, 338 cutaneous SCC) underwent hybridization capture of 315 cancer-related genes and 19 selected introns. These samples underwent genome sequencing, and genomic alterations were determined, as well as the overall tumor mutational burden was calculated. Dr. Jacob and colleagues then compared the differences in the variables between the penile and cutaneous SCC samples.

The group found that metastatic penile SCC patients were generally younger than cutaneous SCC patients. They interestingly noted that there were mutations in several targetable pathways in those patients with penile SCC that could potentially be exploited by second-line treatments in men who are refractory to first line chemotherapy. These included the EGFR pathway, FGFR3 pathway, mTOR pathways, as well as some DNA repair pathways. Overall, the genetic mutations in cutaneous SCC were very different from those in the penile SCC group. One hypothesis to explain the differences is that cutaneous SCC tissue tends to be exposed to UV light in higher doses than does penile SCC tissue.

Dr. Jacob concluded that penile SCC is a unique SCC sub-type with distinctive genomic features that contrast with the much more common cutaneous SCC. Tumor mutational burden was significant higher in the cutaneous SCC group when compared to penile SCC group. They highlighted that there are several pathways which are mutated in both types of SCC which could potentially provide an opportunity for targeted therapies in the future in those patients who are refractory to first line chemotherapy.

Speaker: Joseph M. Jacob, MD, MCR-SUNY Upstate Medical University

Written by: Brian Kadow, MD, Fox Chase Cancer Center at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
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