Although both urachal (U) and nonurachal (NU) bladder adenocarcinomas (adenoCas) share several histologic similarities, they differ in location and sometimes in therapeutic options. We analyzed the differences in genomic alterations (GAs) between these tumor entities, with the aim of identifying potential therapeutic targets for clinical trials.
Overall, 133 U and 328 NU adenoCas were analyzed. Hybrid capture-based comprehensive genomic profiling (CGP) was performed to evaluate all classes of GA. Germline status of GA was predicted using a validated somatic-germline computational method. CGP was performed using the FoundationOne and FoundationOne CDx assays (Foundation Medicine, Inc).
The most frequent GA in both U and NU cohorts included TP53 (86.5% v 81.1%) and KRAS (34.6% v 27.7%). GAs characteristic of colorectal adenoCa, such as SMAD4 (P = .069) and GNAS (P = .071), were more common in U versus NU. Conversely, TERT (P < .01) and RB1 (P = .071) were more prevalent in NU adenoCa. Notably, both U and NU adenoCas exhibited possibly targetable GA in PIK3CA (7.5% v 7.9%) and ERBB2 (6.8% v 7.6%). Biomarkers associated with potential benefit from anti-PD-1/L1 were infrequent. Median tumor mutational burden was 2.6 and 3.5 mutations per megabase for U and NU, respectively, and PD-L1 expression >1% was rare. Genomic ancestry and genomic signature distribution were similar in both tumor types. GAs were most commonly of somatic nature. Limitations include lack of clinical data, tumor heterogeneity, and retrospective nature.
U and NU adenoCAs revealed differences in GA, with PIK3CA and ERBB2 being identified as putative therapeutic targets. Biomarkers of response to anti-PD-(L)1 were uncommon. Results highlight the potential of CGP to personalize treatment options of bladder adenoCa and inform clinical trial designs.
JCO precision oncology. 2024 Aug [Epub]
Antonio Cigliola, Alina Basnet, Joseph M Jacob, Chiara Mercinelli, Valentina Tateo, Damiano Alfio Patanè, Gennady Bratslavsky, Liang Cheng, Petros Grivas, Ashish M Kamat, Philippe E Spiess, Dean C Pavlick, Douglas I Lin, Jeffrey S Ross, Andrea Necchi
Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy., SUNY Upstate Medical University, Syracuse, NY., Department of Pathology and Laboratory Medicine, Department of Surgery (Urology), Brown University, Providence, RI., Division of Hematology/Oncology, Department of Medicine, University of Washington; Fred Hutchinson Cancer Center, Seattle, WA., Department of Urology Under Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX., Department of GU Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL., Foundation Medicine, Inc, Cambridge, MA.