The dose response characteristics of low and intermediate risk prostate cancer treated with external beam radiotherapy

Abstract

In this era of dose escalation, the benefit of higher doses for low-risk prostate cancer remains controversial. For the intermediate risk patients, the literature suggests a benefit from the higher doses. However, the quantitative characterization of the benefit for these patients is scarce. Here we investigated the radiation dose response of PSA control probability in low-risk and intermediate-risk prostate cancer patients treated with radiotherapy alone. Further, we investigated the differences in dose response using the ASTRO definition versus an alternative biochemical failure definition. This study included 235 low-risk and 387 intermediate-risk prostate cancer patients treated with external beam radiotherapy without hormonal treatment from 1987 to 1998. The low-risk patients had 1992 AJCC DRE stage ≤ T2a and PSA ≤10 ng/mL and biopsy Gleason score ≤6. The intermediate-risk patients had one or more of the following: Stage T2b-c, 20ng/mL ≥ PSA >10 ng/mL or Gleason score 7; and without any of the following high-risk features: Stage ≥ T3, PSA >20 ng/mL or Gleason score ≥8. The logistic models were fitted to the data at various time points after treatment, and the dose response parameters were estimated. We used two biochemical failure definitions. The ASTRO PSA failure was defined as three consecutive PSA rises with the time to failure backdated to the mid-point between the nadir and the first rise. We also used an alternative biochemical failure definition: PSA rise ≥2ng/mL above the current nadir PSA (CN+2). The failure date was defined as the time at which the event occurred. Local, nodal, distant relapses and use of salvage hormone were also failures. Based on the ASTRO definition, at 5 years post radiotherapy, the dose required for 50% tumor control, TCD50 (95% C.I.), for low-risk patients is 57.3 (47.6 to 67.0) Gy. The γ50 (95% C.I.) is 1.4 (−0.1 to 2.9) around 57Gy. There is a statistically significant dose response using the ASTRO definition. However, there is no dose response using CN+2 definition for these low-risk patients. For the intermediate-risk patients, using ASTRO definition, the TCD50 is 67.5 (65.5 to 69.5) Gy and the γ50 (95% C.I.) is 2.2 (1.1 to 3.2) around TCD50. Using CN+2 definition, the TCD50 is 57.8(49.8 to 65.9) Gy and the γ50 (95% C.I.) is 1.4(0.2 to 2.5). Recursive partitioning analysis identified two subgroups within the low-risk group as well as the intermediate-risk group: PSA < vs. ≥7.5 ng/mL. Most of the benefit from the higher doses for the low and intermediate-risk group derives from the patients with higher PSA values. For the low-risk group, the dose response curves essentially plateau at 78Gy. There is a dose response using the ATRO definition for the low-risk prostate cancer. However, we found only marginal or no dose response when the CN+2 definition was used. Most of the benefit from the higher doses derived from low-risk patients with higher PSA. In all cases, there will be little projected gain beyond 78Gy for these patients. There is a dose response for the intermediate-risk patients using either the CN+2 or the ASTRO definition. Most of the benefit from the higher doses also derived from the intermediate risk patients with higher PSA. There may still be some room for improvement with further dose increase in this group