ESTRO 2025 - Abstract Book

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Invited Speaker

ESTRO 2025

This is the personal level that touches every patient, next to this we have a more general level where patients can contribute for guiding cancer care. We are or should be present in “guidelines committees”, at the European Association of Urology (EAU) we are a member at the same level as members of EAU, ESTRO, ESNM and others and based on evidence we co-write the guidelines. And, at the level of departments we can be part of a “patient advisory group” to help you when deciding on the clinical trials and the organization of care in your department. But we will, if asked, give our opinion or advice, but we will not decide that is your responsibility.

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Speaker Abstracts Bladder preservation therapy with systemic therapy only: The near future or science fiction? Roberto Iacovelli Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy. UOC of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy Abstract: Non-metastatic muscle-invasive bladder cancer (MIBC) is a condition accounting for up to 20% of all new diagnosis of bladder cancer (BC), which has a high-risk of spreading with the 5-years OS of 72%. Considering the risk of relapse, major clinical guidelines recommended surgery or trimodal therapy (TMT) for primary tumor ablation. Moreover, surgery is generally recommended after a period of neoadjuvant chemotherapy (NAC) which is expected to kill micro metastatic cells, to decrease primary tumor sizes and test in vivo tumor response to treatments which is generally summarized by the pathological complete response (pCR) found after surgery. In BC the efficacy of cisplatin-based NAC has been summarized by the Advanced Bladder Cancer Meta-Analysis Collaboration reporting 13% reduction in risk of death and 5% absolute benefit at 5 years from 45% to 50%. Patients achieving pCR during NAC reported longer OS suggesting this as a surrogate marker for outcome. The inclusion of immunotherapy with the anti-PD(L)1 is the standard of care for treatment of advanced urothelial cancer (aUC) after chemotherapy for responding patients (ie. maintenance) or as subsequent line of therapy for those with progressive diseases. More recently, the combination of enfortumab vedotin (EV) plus the anti-PD1 pembrolizumab has significantly improved the OS (HR 0.47; 95%CI, 0.38 – 0.58; P<0.001); the PFS (HR 0.45; 95%CI, 0.38 – 0.54; P<0.001) and the ORR (67.7% vs. 44.4%; P<0.001) in aUC patients. Based on evidence from aUC, immunotherapy is under investigation in neoadjuvant space both in addition to chemotherapy or to EV and as single agent for patients not eligible to chemotherapy. The NIAGARA trial compared the NAC with or without durvalumab reporting the increase of the pCR from 27.5% to 37.3% as well as of the OS (HR 0.75; 95%CI, 0.59 – 0.93; P=0.01), and of the disease-free survival (DFS; HR 0.68; 95% CI, 0.56 – 0.82; P<0.001). Despite these data, cystectomy remains the standard of care even if it is a life-changing operation due to the need for urinary diversion and is association with a 90-days mortality risk of up to 6–8%. Efforts have been made to find alternative treatments to surgery and TMT has reported comparable outcomes to surgery with 5-year metastasis-free survival of 75% and 74% and the 5-year cancer-specific survival of 84% and 81%, respectively. Unfortunately, the TMT also reported toxicity of any and high grade in 80% and 11% of case, respectively; therefore, risks related to local procedures should be weighed over the increased rate of pCR with the immune-based combinations, arising the question about the need for RT or surgery in all patients with MIBC. The HCRN GU16-257 study tested the combination of nivolumab plus NAC in 76 patients with MIBC. After therapy, 33 (43%) patients had a clinical complete response (cCR) and 32 of these refuse surgery. Eight of 32 patients later underwent cystectomy for local recurrence, 2 patients had NMIBC treated with local therapy and 2 had metastatic disease (one after cystectomy for local relapse). In the RETAIN trial, patients with MIBC eligible to NAC were evaluated for mutations in ATM, ERCC2, FANCC or RB1 genes in tumor tissue and those with mutations and cCR by restaging TUR, urine cytology and imaging post-NAC began pre-defined active surveillance (AS) while the others underwent bladder-directed therapy. After a median follow-up of 41 months, 47 patients (66%) were metastasis-free; in the AS