From diagnosis to therapy: Urological tumors in focus

Annually, the American Society of Clinical Oncology Congress addresses the current state of research on urogenital tumors. The latest study results regarding diagnosis and therapy of prostate cancer, renal cell carcinoma, urothelial carcinoma, testicular cancer and cancer of the penis will be discussed. The focus is on optimal patient care.

In the past, ADT was the standard treatment for advanced prostate cancer (PCa) because it lowered testosterone levels with the goal of slowing tumor growth. Commonly used ADTs include injectable or implantable LHRH agonists and injectable GnRH antagonists. ADT use or options have evolved to include several variants that differ in administration, side effect profiles, occurrence of T surge, speed of testosterone restoration, and cost. Data on patient preferences regarding ADT characteristics remain limited. Therefore, a study included 304 U.S. men over the age of 40 who had health insurance coverage and a PCa diagnosis in the past three years. Four preferences were distinguished: group 1 preferred less impact on sexual activity and faster recovery of testosterone; group 2 preferred infrequent ADT injections, slower recovery of testosterone levels, and lower cost per day; group 3 preferred the once-daily ADT pill; and group 4 wanted lower cost above all.

Significant differences in the importance of ADT traits were found among affected men. This underscores the need to consider individual preferences in shared decision making. It was found that when deciding on PCa therapy, younger, sexually active men consider the potential impact on sexual activity. Among younger men who did not often plan to become sexually active, administrative burden was the most important factor in treatment choice. Some older men considered several features of PCa treatment, including route of administration and time to recovery of testosterone levels, to be important. The subgroup of older men with Medicare insurance paid particular attention to the costs they faced when choosing PCa treatment.

Potential biomarkers detected in urothelial carcinoma

EV is an antibody-drug conjugate (ADC) that targets nectin-4 and is widely used in refractory urothelial carcinoma. However, there is limited data on biomarkers that predict response to EV. Therefore, potential biomarkers of EV response were investigated in a cohort of patients from the UNITE dataset. UNITE is a retrospective cohort study of patients with aUC treated with new agents and includes 16 centers and 592 patients to date. The first EV deployment experience was published in 2021. Now, specifically genetic biomarkers of response have been analyzed on available next-generation sequencing (NGS) tests. Biomarkers examined included tumor mutational burden; alterations in TERTp, TP53, ARID1A, CDKN2A, CDKN2B, FGFR3, ERBB2, COND1, KDM6A, MTAP, PIK3CA, RB1, and TSC1; and DNA damage response (DDR) mutations present in BRCA1, BRCA2, ATM, BARD1, CDK12, CHEK2, PALB2, PPP2R2A, or RAD51B. Observed response (ORR) was determined by investigators for evaluable patients with scans after ≥1 dose of EV.

For all 170 patients, the ORR was 47%, median PFS was six months, median OS was 12 months, and median follow-up was 9.4 months. However, ORR was higher in patients with ERBB2 (67% vs. 44%) and TSC1 (68% vs. 25%) compared with wild type. A shorter median PFS was observed in patients with CDKN2A, CDKN2B, and MTAP alterations, whereas a longer median OS was observed in patients with high TMB.

Immune checkpoint inhibitors in penile carcinoma.

Treatment options for patients with advanced (locally advanced or metastatic) penile carcinoma (PeCa) are limited. It rarely occurs in developed countries, but in developing countries it accounts for 10% of all male cancers. First-line therapy for advanced PeCa remains platinum-based chemotherapy (PBC). However, there are potential reasons why immune checkpoint inhibitors (ICI) may be attractive. Therefore, the safety and efficacy of ICI in advanced PeCa have now been investigated. The analysis is based on a multinational cohort derived from the Global Society of Rare Genitourinary Tumors (GSRGT). Retrospective data were collected on patients with biopsy-proven advanced PeCa who received ≥1 cycle of ICI between 2015 and 2022 at 18 medical centers in the United States, Europe, and Asia. Most patients (n=60, 83%) were ≥2 weeks of age. Treatment line treated and received pembrolizumab (n=23), nivolumab (n=15), cemiplimab (n=15), nivolumab and ipilimumab (n=7), or other anti-PD1/L1-based therapies (n=12). Regarding safety, 18 (25%) patients experienced immune-related adverse events (irAEs) of any grade, 7 (10%) had a grade ≥3, 7 (1%) required steroids, 6 (9%) required hospitalization, and 8 (11%) resulted in treatment discontinuation. Combination therapies were associated with an increased number of TRAEs. Looking at oncologic outcomes, median OS and 24-month OS and median PFS and 24-month PFS were 9.4 months and 19.3% and 2.8 months and 11.2%, respectively. Of the 66 patients in whom a response was detected, the ORR was 7/66 (11%) (2 with complete response, 5 with partial response). Disease was stable in 24% patients, corresponding to a disease control rate of 35%. The median duration of response was 7.9 months. In summary, no new safety signals were observed, but overall antitumor activity was limited.

Congress: Genitourinary Cancers Symposium of the American Society of Clinical Oncology (ASCO-GU)