Long-term toxicity following 3D conformal radiation therapy for prostate cancer from the RTOG 9406 phase I/II dose escalation study

Jeff M Michalski, Kyounghwa Bae, Mack Roach, Arnold M Markoe, Howard M Sandler, Janice Ryu, Matthew B Parliament, William Straube, Richard K Valicenti, James D Cox, Jeff M Michalski, Kyounghwa Bae, Mack Roach, Arnold M Markoe, Howard M Sandler, Janice Ryu, Matthew B Parliament, William Straube, Richard K Valicenti, James D Cox

Abstract

Purpose: To update the incidence of late toxicity of RTOG 9406, a three-dimensional conformal radiation therapy (3DCRT) dose escalation trial for prostate cancer.

Methods and materials: A total of 1,084 men were registered to this Phase I/II trial of 3DCRT (eligible patients, 1,055). The dose for level I was 68.4 Gy; 73.8 Gy for level II; 79.2 Gy for level III; 74 Gy for level IV; and 78 Gy for level V. Patients in levels I to III received 1.8 Gy/fraction, and those in levels IV to V received 2.0 Gy/fraction. Disease group I patients were treated at the prostate only, group 2 patients were treated at the prostate and at the seminal vesicles with a prostate boost, and group 3 patients were treated at the prostate and seminal vesicles. The median follow-up period for surviving patients was 6.1 y (level V) to 12.1 y (level I).

Results: The incidence rates of RTOG grade 3 or less gastrointestinal or genitourinary toxicity were 3%, 4%, 6%, 7%, and 9% in group 1 and 6%, 2%, 6%, 9%, and 12% in group 2 at dose levels of I, II, III, IV, and V, respectively. In group 1, level V patients had a higher probability of grade 2 late or greater gastrointestinal or genitourinary toxicity than those in levels I, II, and III (hazard ratio [HR] = 1.93, p = 0.0101; HR = 2.29, p = 0.0007; HR = 2.52, p = 0.0002, respectively). In group 2, dose level V patients had a higher probability of grade 2 or greater late gastrointestinal or genitourinary toxicity than those in dose levels II, III, and IV (HR = 2.61, p = 0.0002; HR = 2.22, p = 0.0051; HR = 1.60, p = 0.0276, respectively).

Conclusions: Tolerance to high-dose 3DCRT remains excellent. There is significantly more grade 2 or greater toxicity with a dose of 78 Gy at 2 Gy/fraction than with 68.4 Gy to 79.2 Gy at 1.8 Gy/fraction and with 74 Gy at 2 Gy/fraction.

Conflict of interest statement

Conflict of Interest Statement: This work was supported by grants from the National Cancer Institute. Supported by Grants No. RTOG U10 CA21661, CCOP, and Stat U10CA32115 from the NCI No commercial products are described or endorsed by the authors. The authors have no relationship with organizations that would influence the results reported in this manuscript