Selective Bladder Preservation by Combined Modality Protocol Treatment: Long-term Results of 190 Patients With Invasive Bladder Cancer
Reviewer: Mary Kara Bucci, MD The Abramson Cancer Center of the University of Pennsylvania
Source:Urology. 2002 Jul;60(1):62-7 Authors: W. U. Shipley, D. S. Kaufman, E. Zehr, N. M. Heney, S. C. Lane, H. K. Thakral, A. F. Althausen, and A. L. Zietman
The standard of care in the United States for muscle-invasive bladder cancer has traditionally been radical cystectomy. Radiation therapy as a single modality for bladder sparing treatment yielded results that were generally inferior to those achieved by surgery, and has largely been abandoned as a monotherapy approach. Combined modality therapy, using a combination of trans-urethral resection of the bladder tumor (TURBT), radiation, and chemotherapy has been shown to provide superior results to radiation alone. The Massachusetts General Hospital has been a leading institution in bladder preservation with combined modality therapy. This report provides long-term follow-up for 190 patients treated on 5 different tri-modality protocols at this single institution.
Methods and Materials
190 patients treated between 1986 and 1997 on 5 different protocols with 4 regimens.
Patients with T2-T4a tumors were eligible. Patients with hydronephrosis were excluded after 1993.
All treatment regimens include maximum TURBT followed by induction therapy and re-evaluation with urine cytology, cystoscopy, and biopsies, followed by consolidation therapy, which consisted of cystectomy for patients with any evidence of disease or further chemoradiation for those with no evidence of disease(complete responders). Induction and consolidation therapy for complete responders was as follows:
(46 patients) - Induction: 2 cycles of concurrent cisplatin (100 mg/m2, days 1 and 22 of radiation) and radiation (39.6 Gy in once-daily fractions). Consolidation: one addition dose of cisplatin with 25.2 Gy.
(98 patients) - 2 cycles of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV), followed by induction, re-evaluation, and consolidation as per regimen 1.
(29 patients) - Induction: 5FU (425 mg m2, day 1), cisplatin (20 mg/m2/day x 5 days, weeks 1 and 3), and radiation (42.5 Gy in twice-daily fractions). Consolidation: 5FU, cisplatin, and radiation (25 Gy in twice-daily fractions). Both the cystectomy group and the consolidative chemoradiation group received 3 additional cycles of MCV.
(17 patients) - Induction: Cisplatin (20 mg/m2/day x 3 days/week for3 weeks) and 40.8 Gy in 24 fractions given twice-daily. Consolidation: Cisplatin (20 mg/m2/day x 2 days) and 24 Gy in16 fractions given twice-daily. Both groups received 3 additional cycles of MCV.
Patients were seen every 3 months for the following 2 years, with cystoscopy, biopsy, bimanual exam under anesthesia, and urine cytology. Patients were seen every six-months thereafter and evaluated with cytology and cystoscopy.
Median follow-up for surviving patients is 6.7 years (range: 2-13.4).
Visibly complete TURBT was possible in 57% of patients.
66 patients (35%) underwent radical cystectomy, 41 for an incomplete response to induction therapy and 25 as a salvage procedure for recurrent invasive disease.
Toxicity from neoadjuvant MCV was high, with 19 patients experiencing neutropenia and/or sepsis, including 4 deaths, as reported by Shipley et. al. JCO 16(11): 3576-3583, 1998.
5- and 10- year overall survivals for all patients are 54% and 36%.
5- and 10- year disease-specific survivals (DSS) are 63% and 59%.
5- and 10- year DSS for patients undergoing cystectomy are 48% and 41%.
Of the 121 patients who had an initial complete response to induction therapy and were able to keep their bladders, 60% remain disease free, 24% developed a superficial recurrence, and 16% developed an invasive recurrence, resulting in 72 patients who are continuously free of disease with intact bladders.
The overall 5- and 10- year survivals for this group of patients are comparable to both those achieved in other tri-modality, bladder conserving series as well as those reported in prospective cystectomy series for patients of comparable stage disease. Patients who did experience a bladder recurrence were effectively salvaged with cystectomy. The authors conclude that a bladder-sparing approach with trimodality therapy, close follow-up and prompt cystectomy for salvage is a safe and effective alternative to cystectomy.