Redefining Rare Genitourinary Cancers: An Initiative Led by the Global Society of Rare Genitourinary Tumors.

Rare cancers account for 20-25% of all cancers diagnosed annually but there is no consensus on the definition of a rare cancer and substantial geographic heterogeneity. The Global Society of Rare Genitourinary Tumors is dedicated to education and research for rare genitourinary tumors.

Genomic Profiles and Clinical Outcomes of Penile Squamous Cell Carcinoma With Elevated Tumor Mutational Burden.

Importance: Tumor mutational burden (TMB) is a putative biomarker of efficacy for immune checkpoint inhibitor (ICI) therapies of solid tumors, but not specifically for penile squamous cell carcinoma (PSCC). Objective: To characterize biomarker features and ICI therapy outcomes associated with high TMB in PSCC in the routine clinical practice setting. Design, Setting, and Participants: In this cohort study, 397 PSCC cases were analyzed to identify genomic alterations in more than 300 cancer-associated genes and genomic signatures, including TMB, using a hybrid capture-based comprehensive genomic profiling assay. Tumor mutational burden was categorized as low (<10 mutations per megabase [mut/Mb]), high (10-19 mut/Mb), or very high (≥20 mut/Mb). Germline status of genetic alterations was predicted using a validated somatic-germline computational method. Clinical outcomes of patients with metastatic PSCC receiving first-line ICI were abstracted using the deidentified nationwide Clinico-Genomic Database (CGDB) from January 1, 2011, through December 31, 2022. Exposure: Comprehensive genomic profiling was performed using FoundationOne and FoundationOne CDx assays from Foundation Medicine Inc. Main outcomes and measures: The spectrum of genetic alterations by TMB level in PSCC, the percentage of germline genetic alterations, and the outcome (overall survival with routine clinical treatment) by TMB of chemotherapy-naive patients with PSCC who received ICI treatment up front were assessed in this descriptive study. Results: Among 397 patients (median [IQR] age, 65 [54-73] years; 266 [67.0%] of European, 83 [20.9%] of admixed American, and 34 [8.5%] of African or other genomic ancestry), the median (IQR) age (eg, 65 [53-73] years for low TMB vs 68 [61-78] years for TMB ≥10 mut/Mb) and genomic ancestry distribution (eg, European 228 of 339 [67.3%] for low TMB vs 38 of 58 [65.5%] for TMB ≥10 mut/Mb) were similar between TMB subgroups. There were 339 PSCC cases (85.4%) with low TMB, 40 cases (10.1%) with high TMB, and 18 cases (4.5%) with very high TMB. Comparisons of TMB of 10 mut/Mb or higher vs low TMB showed an enrichment of genetic alterations in PIK3CA (48.3% vs 18.3%; P < .001) and KMT2D (29.3% vs 7.7%; P < .001) and less frequent genetic alterations in CDKN2A (25.9% vs 45.7%; P = .05). Most genetic alterations did not co-occur. Human papillomavirus identification was more frequent as TMB increased: 28.3% for low TMB, 50.0% for high, and 72.2% for very high. In total, 95 of 1377 genetic alterations (6.9%) were germline. Of 10 patients identified from the CGDB receiving frontline ICIs, median (IQR) follow-up was 9.9 months. Four patients had overall survival with clinical treatment of more than 12 months, including 2 of 3 patients with TMB of 10 mut/Mb or higher. Conclusions and Relevance: In this cohort study of advanced metastatic PSCC based on TMB levels, significant differences were observed for biomarkers in nearly 15% of patients with a TMB of 10 mut/Mb or higher. Germline testing and ICI-based therapy should be integrated into the management of selected PSCC cases.

Neoadjuvant Pembrolizumab and Radical Cystectomy in Patients with Muscle-Invasive Urothelial Bladder Cancer: 3-Year Median Follow-Up Update of PURE-01 Trial.

PURPOSE: The PURE-01 study (NCT02736266) pioneered the neoadjuvant immune-checkpoint inhibitor (ICI) therapy before radical cystectomy (RC) in patients with muscle-invasive urothelial bladder carcinoma (MIBC). We herein present the survival outcomes after a median follow-up of three years. PATIENTS AND METHODS: The intention-to-treat (ITT) population included 155 patients. Event-free survival (EFS) was defined as the time from pembrolizumab initiation until radiographic disease progression precluding RC, initiation of neoadjuvant chemotherapy, recurrence after RC, or death. Further outcomes were recurrence-free survival (RFS) post-RC and overall survival (OS). Multivariable Cox regression analyses for EFS were performed. Kaplan-Meier analyses compared EFS outcomes according with baseline programmed cell-death-ligand-1 (PD-L1) combined positive score (CPS) and according to the molecular subtypes. RESULTS: After a median (interquartile range, IQR) follow-up of 39 (30-47) months, 36-month EFS and OS were 74.4% [95% confidence interval (CI), 67.8-81.7] and 83.8% (95% CI, 77.8-90.2) in the ITT population, respectively. Overall, 143 (92.3%) patients underwent RC. Within the cohort of patients who did not receive additional chemotherapy (N = 125), 36-month RFS was 96.3% (95% CI, 91.6-100) for patients achieving a ypT0N0, 96.1% (95% CI, 89-100) for ypT1/a/isN0, 74.9% (95% CI, 60.2-93) for ypT2-4N0, and 58.3% (95% CI, 36.2-94.1) for ypTanyN1-3 response. EFS was significantly stratified among PD-L1 tertiles (lower tertile: 59.7% vs. medium tertile: 76.7% vs. higher tertile: 89.8%, P = 0.0013). The claudin-low and basal/squamous subtypes displayed the lowest rates of events. CONCLUSIONS: At a median follow-up of three years, PURE-01 results further confirm the sustained efficacy of neoadjuvant pembrolizumab before RC. PD-L1 expression was the strongest predictor of sustained response post-RC.

Custo de tratamento do câncer de próstata resistente à castração por meio da aplicação da técnica Delphi no Sistema de Saúde Suplementar brasileiro / Cost of treating castration-resistant prostate cancer by applying the Delphi method to the Brazilian Private Healthcare System

Objetivo: Estimar os custos do tratamento de pacientes com câncer de próstata não metastático resistente à castração (nmCRPC) e metastático resistente à castração (mCRPC) no Sistema de Saúde Suplementar brasileiro. Métodos: Foi realizada uma busca na literatura para avaliar os dados já disponíveis do custo do tratamento do câncer de próstata no Brasil. Como os dados são escassos, optou-se por utilizar a técnica Delphi com seis médicos oncologistas para levantamento do uso dos recursos. O painel Delphi contou com três etapas, sendo duas on-line e uma presencial, abordando recursos, frequência e porcentagem de uso de exames de imagem e laboratoriais, e dados hospitalares (consultas, pronto-socorro, internações ­ clínica, cirúrgica e em unidade de terapia intensiva). Também foram solicitados dados de padrões de tratamento do câncer de próstata. Por fim, dados do manejo das metástases foram requeridos. Por meio das informações coletadas, foi desenvolvido o microcusteio do câncer de próstata resistente à castração na perspectiva do Sistema de Saúde Suplementar. Resultados: O custo total de tratamento da jornada do paciente com câncer de próstata resistente à castração foi igual a 480.497,25 BRL, e o tratamento unicamente da doença não metastática foi de 189.832,79 BRL e o da doença metastática, de 290.664,46 BRL. Conclusão: Os custos do tratamento de câncer de próstata metastático são substancialmente superiores aos custos do tratamento do paciente não metastático resistente à castração de alto risco, o que parece justificar economicamente o uso de medidas que previnam ou adiem o surgimento de metástases.

Objective: To estimate the treatment costs for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-resistant prostate cancer (mCRPC) within the Brazilian private healthcare system. Methods: A literature search was performed to obtain currently available data on prostate cancer treatment costs in Brazil. As national data are scarce, a Delphi method with a specialist board was chosen with six oncologists for resource estimations. The Delphi panel had three steps: two online and one in-person, addressing what resources, frequencies, and percentages of use of imaging and laboratory exams, hospital data (including medical appointments, emergency room, hospitalizations - clinical, surgical and Intensive Care Unit). Data on prostate cancer treatment patterns were also requested. Finally, metastasis management data was required. Using the collected data, we developed a micro-costing model of castration-resistant prostate cancer in Brazil. Results: The total cost for the entire castration-resistant prostate cancer patient journey was 480.497,25 BRL, with the non-metastatic disease alone costing 189.832,79 BRL and the metastatic disease costing 290.664,46 BRL. Conclusion: The costs of treating metastatic prostate cancer are substantially higher than the treatment of high-risk castration-resistant non-metastatic patients, which seems to economically justify the use of measures that prevent or postpone metastasis.