Is trimodal therapy the current standard for muscle-invasive bladder cancer?

OBJECTIVE: The aim of this review is to summarize the current evidence and future perspectives of bladder-sparing treatment for MIBC. METHODS: A non-systematic literature search in Medline/Pubmed was performed in October 2023 with the following keywords "bladder cancer", "bladder-sparing", "trimodal therapy", "chemoradiation", "biomarkers", "immunotherapy", "neoadjuvant chemotherapy", "radiotherapy". RESULTS: Urology guidelines recommend radical cystectomy as the standard curative treatment for muscle-invasive urothelial bladder cancer, reserving radiotherapy for patients who are unfit or who want to preserve their bladder. Given the morbidity and mortality of cystectomy and its impact on quality of life and bladder function, modern oncologic therapies are increasingly oriented toward organ preservation and maximizing functional outcomes while maintaining treatment efficacy. Trimodal therapy, which incorporates maximal transurethral resection followed by radiotherapy with concurrent radiosensitizing chemotherapy, is an effective regimen for bladder function preservation in well-selected patients. Despite the absence of comparative data from randomized trials, the two approaches seem to provide comparable oncologic outcomes. Studies are evaluating the expansion of eligibility criteria for trimodal therapy, the optimization of radiotherapy and immunotherapy delivery to further improve outcomes, and the validation of biomarkers to guide bladder preservation. CONCLUSIONS: Trimodal therapy has shown acceptable outcomes for bladder preservation; therefore, it provides a valid treatment option in well-selected patients.

Sarcoidosis-like reactions in cancer patients treated with immune checkpoint inhibitors: experience in a Spanish hospital

Background Immune checkpoint inhibitors (ICI) have been associated with several immune-related adverse events, including sarcoidosis-like reactions (SLR). SLR, which has a low prevalence but an increasing incidence, is similar to sarcoidosis in terms of histology, and clinical and radiological manifestations. The most commonly affected organs are hilar and mediastinal lymph nodes and skin. SLR is an exclusion diagnosis, so a lymph node biopsy can be useful to distinguish between tumor progression and SLR, particularly in tumors in which nodal involvement is very common. Patients and methods We performed a retrospective analysis of SLR in all cancer patients receiving ICIs in our institution between January 2016 and June 2020. Results Among the 1063 treated patients, seven experienced SLR, four of whom were symptomatic (cough, skin lesions, arthralgia), with time to onset ranging from 1.5 to 6.7 months after ICI initiation. All seven patients had bilateral hilar lymphadenopathy, and granulomatous reactions in five of the six patients with lymph node biopsies. SLR improved in all patients, including four patients who continued with ICI. Three patients received corticosteroids and/or stopped ICI therapy. Four of these patients had partial responses at the time SLR was identified. Conclusion Management of SLR lacks a consensus recommendation, although corticosteroids and/or stopping the ICI are generally implemented. The potential consequences of stopping anticancer treatment should be taken into consideration, particularly in the absence of clear management recommendations (AU)

Sarcoidosis-like reactions in cancer patients treated with immune checkpoint inhibitors: experience in a Spanish hospital.

BACKGROUND: Immune checkpoint inhibitors (ICI) have been associated with several immune-related adverse events, including sarcoidosis-like reactions (SLR). SLR, which has a low prevalence but an increasing incidence, is similar to sarcoidosis in terms of histology, and clinical and radiological manifestations. The most commonly affected organs are hilar and mediastinal lymph nodes and skin. SLR is an exclusion diagnosis, so a lymph node biopsy can be useful to distinguish between tumor progression and SLR, particularly in tumors in which nodal involvement is very common. PATIENTS AND METHODS: We performed a retrospective analysis of SLR in all cancer patients receiving ICIs in our institution between January 2016 and June 2020. RESULTS: Among the 1063 treated patients, seven experienced SLR, four of whom were symptomatic (cough, skin lesions, arthralgia), with time to onset ranging from 1.5 to 6.7 months after ICI initiation. All seven patients had bilateral hilar lymphadenopathy, and granulomatous reactions in five of the six patients with lymph node biopsies. SLR improved in all patients, including four patients who continued with ICI. Three patients received corticosteroids and/or stopped ICI therapy. Four of these patients had partial responses at the time SLR was identified. CONCLUSION: Management of SLR lacks a consensus recommendation, although corticosteroids and/or stopping the ICI are generally implemented. The potential consequences of stopping anticancer treatment should be taken into consideration, particularly in the absence of clear management recommendations.

Validation of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model for first-line pazopanib in metastatic renal carcinoma: the Spanish Oncologic Genitourinary Group (SOGUG) SPAZO study.

BACKGROUND: Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice. PATIENTS AND METHODS: Data of 278 patients, treated with first-line pazopanib for mRCC in 34 centres in Spain, were locally recorded and externally validated. Mean age was 66 years, there were 68.3% male, 93.5% clear-cell type, 74.8% nephrectomized, and 81.3% had ECOG 0-1. Metastatic sites were: lung 70.9%, lymph node 43.9%, bone 26.3%, soft tissue/skin 20.1%, liver 15.1%, CNS 7.2%, adrenal gland 6.5%, pleura/peritoneum 5.8%, pancreas 5%, and kidney 2.2%. After median follow-up of 23 months, 76.4% had discontinued pazopanib (57.2% due to progression), 47.9% had received second-line targeted therapy, and 48.9% had died. RESULTS: According to IMDC prognostic model, 19.4% had favourable risk (FR), 57.2% intermediate risk (IR), and 23.4% poor risk (PR). No unexpected toxicities were recorded. Response rate was 30.3% (FR: 44%, IR: 30% PR: 17.3%). Median progression-free survival (whole population) was 11 months (32 in FR, 11 in IR, 4 in PR). Median and 2-year overall survival (whole population) were 22 months and 48.1%, respectively (FR: not reached and 81.6%, IR: 22 and 48.7%, PR: 7 and 18.8%). These estimations and their 95% confidence intervals are fully consistent with the outcomes predicted by the IMDC prognostic model. CONCLUSION: Our results validate the IMDC model for first-line pazopanib in mRCC and confirm the effectiveness and safety of this treatment.