Tumor Samples in Urethral Cancer Reveal Potential Treatment Targets

Carcinoma of the urethra is an uncommon type of cancer, the rarest of the urologic cancers. Patients sometimes do not have symptoms, but most do. Treatment options have been limited, but a precision medicine approach may improve outcomes.

A recent study appearing Wednesday in Urologic Oncology outlined results from comprehensive genomic profiling of tumor samples from 127 patients with metastatic urethal cancer, examining genomic alterations and cataloging the frequency of immunotherapy biomarkers.

Study authors, from SUNY Upstate Medical University and Foundation Medicine, wrote “results indicated that the histologic subtypes feature contrasting genomic profiles with distinct potential for targeted and immunotherapy.”

Patients evaluated included 49 (39%) with urothelial cancer, 31 (24%) with squamous, 24 (19%) with adenocarcinomas NOS (not otherwise specified), and 12 (9%) with clear cell. Urothelial and squamous cancer were more common in men; while adenocarcinomas and clear cell cancers were more common in women.

The most frequent targetable genomic alteration seen was PIK3CA, followed by mTOR and PTEN. Other targetable genomic alterations included ERBB2, seen in 6% of urothelial cancers, 3% of squamous cancers, and 12% of adenocarcinoma; FGFR1-3, seen in 3 of squamous cancers; BRAF, seen in 3% of adenocarcinomas, PTCH1, seen in 8% of clear cell, and MET, seen in 8% of clear cell.

Authors said tests showed greater potential for immunotherapy benefit in urothelial cancer and squamous, “possibly reflecting their higher genomic alteration/tumor status,” and therapeutic potential associated with higher tumor mutational burden.

“Microsatellite instability high status was absent throughout,” the authors said.

The authors wrote that comprehensive genomic profiling may benefit patients with advanced urethral cancer and could help clinicians match the right patients with the right therapy in future adjuvant, neoadjuvant, and metastatic disease trials.

Foundation Medicine funded the study.