Sequential Chemotherapy Followed by Ultrahypofractionated Radiotherapy for Muscle-Invasive Bladder Cancer

Muscle-invasive bladder cancer (MIBC) is a potentially lethal disease for which radical cystectomy with appropriate systemic therapy remains a standard curative approach in medically fit patients. . However, Half of bladder cancer cases are diagnosed in patients aged over 75 years, many of whom are not fit for major surgery owing to their performance status and comorbidities . A substantial proportion of bladder cancer cases occur in older adults (there is no single universal age cutoff for the term older adults, but several commonly used definitions exist: WHO: generally refers to people aged 60 years or older, particularly in low- and middle-income countries, while in clinical and research settings: ≥65 years is frequently used as the operational definition of older adults, especially in oncology and geriatric medicine), and advanced age is frequently accompanied by comorbidities and frailty that may limit eligibility for radical surgery or multimodality treatment . Bladder-preserving treatment incorporating maximal transurethral resection of bladder tumor (TURBT) and definitive radiotherapy is therefore an important treatment option in selected patients.

Inclusion Criteria: 1. Histologically confirmed urothelial carcinoma of the urinary bladder 2. Muscle-invasive disease, preferably clinical stage cT2-T4a, N0, according to TNM staging system. 3. No evidence of distant metastatic disease (M) . 4. Age ≥65 years including medically unfit patients for radical cystectomy or radical daily radiotherapy for any reason including but not limited to performance status, comorbidity or patient preferance . 5. ECOG performance status 0\_ 3. 6. Patients must have undergone maximal safe TURBT, with documentation of detrusor muscle in the specimen whenever technically feasible. 7. \_Creatinine clearance (CrCl) ≥30 mL/min for patients receiving a carboplatin-based regimen. CrCl ≥40 mL/min for patients receiving fractionated cisplatin-based chemotherapy. 8- Eligible patients would have an expected survival of greater than 6 months, be willing to accept assessment with cystoscopy following radiotherapy completion and be able to attend for follow-up Exclusion Criteria: 1. Nodal disease and distant metastatic disease (M1). 2. Previous radiotherapy to the pelvis or any contraindication for pelvic RT including IBD. 3. Previous systemic chemotherapy for the current MIBC. 4. Uncontrolled active infection, moderate to severe hydronephrosis, invasion of prostatic urethra, diffuse TIS throughout the bladder, tumor size \>6 cm. 5. Active or history of other malignancy within 2 years of recruitment except for non-melanomatous skin carcinoma, previous non-muscle invasive bladder tumors and low-risk prostate cancer (as defined by NCCN risk stratification as T1/T2a, Gleason 6, PSA \