shows the number of patients, median follow up for all prostate and surviving patients, median PSA, race, KPS and Gleason Score of patients on RTOG 85-31, 86-10, and 92-02 by treatment arm. Given that these were phase III randomized trials, there is no statistically significant difference in any of these parameters except PSA in 86-10 since this parameter was not part of the routine practice at the outset of the study, and therefore, not a requirement for study entry. The median follow up for 85-31 was 8.1 years and 11.1 for living patients. Median follow up for 86-10 was 6.9 years and 12.2 for living patients. Median follow up for 92-02 was 8.1 years with 9.9 years for living patients. Median age was 70 across all three studies. The median PSA value was approximately 20 for all 3 studies, and a minimum of 42% of patients had a GS of ≥ 7. Both PSA and GS revealed the high risk and/or locally advanced nature of the tumors in these studies.
Maximum late GI, GU, and other toxicity as well as maximum toxicity per patient is shown in by study. Regarding GI toxicity, there were 3 deaths (grade 5 toxicity), all of which occurred in study 92-02. One was in the short term hormone arm, and two were in the long term hormone arm. The first was a sigmoid perforation with sepsis and death, another a small bowel obstruction with surgical resection and ultimate peritonitis and death, and the last was a patient with rectal bleeding and known radiation proctitis who refused laser treatment as well as transfusion, and ultimately died. Grade 4 GI toxicity occurred in < 1 – 1% of patients in all 3 studies. The most common types of grade 4 GI toxicity were proctitis and rectal bleeding.
Regarding maximum GU toxicity, there were no deaths, and < 1 – 2% of patients experienced grade 4 toxicity, the most common types being cystitis and hematuria.
Late other toxicity showed no deaths, and < 1–2% of patients had grade 4 complications. These consisted of osteoporosis, malignant ascites, rectovesicle fistula, pain, and rectourethral fistula. There were no statistically significant differences in maximum toxicity per patient for any of the three studies when analyzed by treatment arm.
shows the late grade 3+ toxicity by treatment grouping of RT only, RT+STH, and RT + LTH. Maximum grade 3+ late GI toxicity was 4% for RT only, 1% for RT+STH, and 3% for RT + LTH. Maximum grade 3+ late GU toxicity was 9%, 5%, and 6% for RT only, RT+STH, and RT + LTH, respectively. Maximum grade 3+ late other toxicity was 2%, 1%, and 1% respectively for RT alone, RT+STH, and RT + LTH.
Toxicity Data by RT vs RT+STH vs RT+LTH
reports the results of the multivariate analysis with two covariates, age (≤ 70 vs. > 70) and treatment type (RT alone, RT+STH, and RT + LTH). It shows that age > 70 was statistically significantly associated with a decrease in late total grade 3+ toxicity (HR= 0.78, p=0.0476) after adjusting for treatment type. Patients treated with RT+STH had a statistically significant lower probability of grade 3+ GI, GU, and other toxicity compared to RT alone when adjusting for age (HR=0.33, p = .00006; HR=0.57, p=0.0037; HR=0.30, p=0.0127, respectively). RT+STH had a statistically significant decrease in grade 3+ late total toxicity over RT alone (HR=0.54, p = 0.0001). Patients treated with RT+LTH had a statistically significant lower probability of grade 3+ GU toxicity compared to RT alone (HR=0.67, p=0.023). Also, RT + LTH showed a trend towards decrease in late total grade 3+ toxicity (HR= 0.77, p = 0.0566). No other statistically significant differences were seen.
Cox Proportional Hazard Models for Time to Late Grade 3+ Toxicity
The time to grade 3+ late GI, GU, and other toxicity is shown in , , and respectively. As predicted, the majority of grade 3+ late GI toxicity occurs in the first 1–3 years, whereas the GU toxicity occurs over a longer period of time, 2–5 years. RT+STH was statistically significantly associated with a decreased time to grade 3+ late GI toxicity (p = 0.006). Time to grade 3+ late GU toxicity shown in reveals a statistically significant difference in time to grade 3+ late GU toxicity for RT+STH and LTH + RT compared to RT alone (p = 0.0037 and p = 0.0230, respectively).
Time to Late Grade 3+ GI Toxicity By Treatment Type
Time to Late Grade 3+ GU Toxicity By Treatment Type
Time to Late Grade 3+ Other Toxicity By Treatment Type