RTOG 9706: Initial report of a phase I/II trial of bladder-conservation employing TURB, accelerated irradiation sensitized with cisplatin followed by adjuvant MCV chemotherapy

Ryan Smith, MD
University of Pennsylvania Cancer Center
Last Modified: November 4, 2001

Presenter: M. P. Hagan
Affiliation: Medical College of Virginia

Background
The standard of care for muscle invasive bladder cancer is radical cystectomy +/- adjuvant chemotherapy with or without radiation. However, there is much interest in organ preserving therapy with combined chemotherapy and radiation therapy.

Materials and Methods

Prospective study of 52 patients, staged T2-T4aN0M0.

All underwent TURBT followed by induction chemoradiation therapy.

During induction therapy, cisplatin (20mg/m2) is given over the 1st three days of each week.

Radiation is given over 13 days, consisting of 1.8 Gy to the whole pelvis (AM) and 1.6 Gy to the tumor volume 4-6 hours later. Hence, total tumor dose during induction is 40.8 Gy to the tumor and 20 Gy to the whole pelvis.

Patients were cystoscopically reevaluated 3 weeks after induction. Those with a complete response (CR) completed chemoradiation. Those with residual tumor had immediate cystectomy.

All patients received adjuvant MCV chemotherapy.

Results

Total of 32 patients (74%) had CR after induction.

Projected OS is 83% at 12 months and 65% at 24 months.

Bladder intact survival is 68% at 12 months and 52% at 24 months.

70% received treatment as per the protocol.

11% had Grade 3 toxicity during the induction phase, and 35% had Grade 3 toxicity during the adjuvant phase.

Only 20 patients received adjuvant MCV chemotherapy, but 8 of these (40%) had Grade 4 neutropenia/thrombocytopenia

Author's Conclusions

There was a CR rate of 74%, comparable to many other bladder sparing regimens.

Projected OS, LR control, and bladder intact survival also consistent with previous bladder conserving studies

Induction protocol was well tolerated

Only 42% completed adjuvant MCV therapy

Clinical/Scientific Implications
This is a concurrent chemoradiation study employing BID radiation. A difference is the long (3 week) break between induction therapy and reevaluation. This could have a positive influence on CR by allowing for further tumor response or a negative overall effect by allowing for tumor regrowth between therapies. However, the results are similar to many other bladder conserving regimens to treat muscle invasive bladder cancer. More time is needed to allow for the data to mature as the follow-up is relatively short. This is a small trial, so additional studies will be required to confirm these findings. This study was well tolerated until the adjuvant therapy phase, when the MCV chemotherapy induced much toxicity.