PURPOSE: The evolving treatment landscape of muscle-invasive bladder cancer (MIBC) increasingly warrants novel trial design to evaluate perioperative strategies aimed at bladder preservation. To establish standardized outcome measures for evaluating organ preservation strategies in MIBC, the International Bladder Cancer Group (IBCG) and the Global Society of Rare Genitourinary Tumors (GSRGT) assembled an international, multidisciplinary consensus panel. METHODS: The IBCG and GSRGT gathered global bladder cancer experts and patient advocates to establish a framework for risk-adapted bladder-sparing treatment approaches for MIBC. Working groups reviewed the literature and developed draft recommendations, which were discussed at a live meeting in December 2024 in Milan. This was followed by voting by the members using a modified Delphi process. Recommendations achieving ≥75% agreement during the meeting were further refined and presented. RESULTS: Clinical complete response (cCR) definition should encompass the absence of high-grade malignancy on pathology and malignant cells on urine cytology and no evidence of local or metastatic disease on cross-sectional imaging. Although cCR remains immature as a primary or coprimary end point in registrational trials, it could serve as a suitable end point in early-phase studies and risk-adapted investigations. Event-free survival (EFS) remains the preferred primary end point as it could reliably capture the durability of clinically meaningful benefit after omittance of surgical consolidation or chemoradiation. Given the composite nature of EFS, events should be prespecified, evaluated in an intention-to-treat approach, and meticulously collected. Continuous assessment of individual patient preferences should begin at the outset of perioperative therapy discussions, with informed decision making prioritized throughout. CONCLUSION: The consensus definition of cCR and the framework presented in this study can serve as a foundation for thorough testing of risk-adapted bladder-sparing treatment paradigms for MIBC.

The effect of multiple doses of lomefloxacin (400 mg twice a day) on the clearance of theophylline and the urinary excretion of its metabolites was investigated in 15 healthy male subjects. Concentrations of theophylline in plasma were measured by TDx (Abbott Diagnostics, Mississauga, Ontario, Canada). Urinary excretion of theophylline and its three major metabolites and lomefloxacin in plasma were assayed by high-performance liquid chromatography. Total theophylline clearance remained unchanged before lomefloxacin treatment and after lomefloxacin single- and multiple-dose treatments (58.02, 56.57, 54.07 ml/min, respectively). The urinary recovery of unchanged theophylline and its major metabolites stayed stable during the study. We conclude that lomefloxacin can be added to the list of fluoroquinolones that can be administered safely with theophylline.

The influence of multiple doses of fleroxacin on the plasma clearance and the urinary excretion of theophylline was studied in 19 young and 18 elderly male volunteers. A theophylline dosage individualized to obtain a mean theophylline concentration in plasma of 10 +/- 3 micrograms/ml was administered for 1 week to each subject. At week 2, oral fleroxacin (400 mg once daily) was added. Theophylline concentrations in plasma were measured with TDx (Abbott Diagnostics, Mississauga, Ontario, Canada), and urinary excretion of theophylline and its three major metabolites was measured by high-performance liquid chromatography. Total theophylline clearance remained essentially unchanged throughout the study period (3.5 and 2.9 liters/h in the young and the elderly, respectively) both after a single fleroxacin dose and after multiple doses. Although significant changes occurred in the urinary excretion of unchanged theophylline and its metabolites after a single fleroxacin dose, no changes were observed after multiple doses. Side effects consisted mainly of gastrointestinal and sleep disturbances, more related to theophylline; photosensitivity was observed in six subjects and was attributed to fleroxacin. We conclude that fleroxacin may be administered concomitantly with theophylline in either young or elderly patients. Close monitoring of theophylline concentrations in serum should be performed, particularly in patients with chronic obstructive pulmonary disease, for whom data are currently lacking.

Purpose:Second malignancy is a rare but potentially lethal event after prostate brachytherapy, but data remain scarce on its long-term risk. The objective of this study is to estimate the number of...