Improved biochemical relapse-free survival with increased external radiation doses in patients with localized prostate cancer: the combined experience of nine institutions in patients treated in 1994 and 1995.

Purpose: To study the radiation dose-response as determined by Kaplan-Meier prostate-specific antigen (PSA) disease-free survival (PSA-DFS) estimates in patients with stage T1-T2 prostate cancer treated within a 2-year period (1994-1995).

Methods: Nine institutions combined data on 4839 patients with stage T1 and T2 adenocarcinoma of the prostate who received > or =60 Gy external beam radiation therapy (RT) as sole treatment. No patient received neoadjuvant androgen deprivation or planned adjuvant androgen deprivation. Of the 4839 patients, 1325 were treated in 1994 and 1995; 1061 were treated with <72 Gy and 264 with > or =72 Gy. The median RT doses for the <72 Gy and the > or =72 Gy groups were 68.4 Gy and 75.6 Gy, respectively. The median follow-up for the <72 Gy and the > or =72 Gy groups were 5.8 and 5.7 years, respectively. Risk groups, defined on the basis of T stage, pretherapy PSA level, and biopsy Gleason score (GS), were as follows: low risk--T1b, T1c, T2a, GS < or =6 and PSA < or =10 ng/mL; intermediate risk--T1b, T1c, T2a, GS < or =6 and PSA >10 ng/mL but < or =20 ng/mL or T2b, GS < or =6 and PSA < or =20 ng/mL or GS 7 and PSA < or =20 ng/mL; high risk--GS 8-10 or PSA >20 ng/mL. The endpoint for outcome analysis was PSA-DFS at 5 years after therapy using the American Society for Therapeutic Radiology and Oncology failure definition.

Results: Patients receiving > or =72 Gy had significantly more advanced cancers. The proportion of stage T2b/T2c cancers in the > or =72 Gy group was 42% compared with 32% in the <72 Gy group (p = 0.027). The mean pretherapy PSA was 11.4 ng/mL in the > or =72 Gy group compared with 10.7 ng/mL in the <72 Gy group (p = 0.001). The proportion of GS > or =8 cancers in the > or =72 Gy group was 9% compared with 7% in the <72 Gy group (p = 0.309). Overall, 15% of patients receiving <72 Gy had high-risk disease, compared with 22% of patients receiving > or =72 Gy (p = 0.034). The > or =72 Gy group had a greater number of follow-up PSA levels (mean 10.6/patient) compared with the <72 Gy group (mean 9.6/patient) (p = 0.007). For all 1325 patients, the 5- and 8-year PSA-DFS estimates were 64% and 62%, respectively. The 5-year PSA-DFS estimates for <72 Gy vs. > or =72 Gy were 63% vs. 69%, respectively (p = 0.046). Multivariate analysis for factors affecting PSA-DFS was performed for all cases using the following variables: pretherapy PSA (continuous), biopsy GS (continuous), stage (T1 vs. T2), radiation dose (continuous), and radiation technique (three-dimensional conformal vs. conventional). Pretreatment PSA (p < 0.001, chi-square 112.2), GS (p < 0.001, chi-square 12.8), radiation dose (p < 0.001, chi-square 13.5), and stage (p = 0.007, chi-square 7.2) were independent predictors of outcome. Radiotherapy technique was not (p = 0.50).

Conclusion: Differences in PSA-DFS estimates observed in multiple retrospective series have been attributed to differences in follow-up duration between patients treated to conventional doses (longer follow-up intervals) and those treated to higher doses (shorter follow-up intervals). In this report, the median follow-up duration in the > or =72 Gy group was essentially identical to the <72 Gy group, because the study included a large number of patients treated consecutively during a narrow time range (1994-1995). With similar follow-up duration, higher than conventional radiotherapy doses were associated with improved PSA-DFS when controlled for the influence of pretreatment PSA levels, biopsy GS, and clinical T stage.