Radiation Dose & Toxicity
With reference to the three randomized studies (see sections 'Adjuvant RT' and 'SRT versus ART'),[33,51,54] a dose of 60–64 Gy for external-beam ART is the consensus in the German S3-guidlines. The situation is less clear for SRT (Table 1). To avoid radiation toxicity, most SRT studies do not exceed 70 Gy. It has been suggested that at least 66 Gy should be administered.[35,84,201] In a meta-analysis, the dose to achieve 50% tumor control in terms of 5-year bNED was calculated to be 66.8 Gy with a further gain of 3.8% per Gy. Notably, that study predicts a 6 Gy lower 50% isoeffective dose for ART than for SRT, which, according to recently published model calculations, should enable a tangible reduction of toxicity to the gastrointestinal (GI) and genitourinary (GU) tract. For R1 patients who are candidates for ART, such a dose reduction may have a positive impact on the quality of life. However, in a comparison of ART with median 70.2 Gy and SRT with median 72 Gy, grade ≥2 and grade 3 late urinary toxicity were nearly identical (23.9 vs 23.7% and 12 vs 10%) after 8 years. Even 76 Gy have been deemed safe with intensity-modulated SRT, yielding a 5-year risk of grade 2–3 toxicity of 22 and 8% for GU and GI symptoms, respectively. Monitoring the PSA over the course of radiation can distinguish RT responders and nonresponders, and it has been suggested to increase the dose for responders, assuming that they are likely to profit from the more aggressive treatment (while reducing the dose might put cure rates at risk).
Based on published data from 13 studies on nearly 1800 patients, a nonlinear model for normal tissue complication probability suggests >5% grade ≥3 GI reactions above 68 and 69 Gy in the GU and GI tract, respectively. However, the text sources include only one study with a treatment dose >69 Gy and figures on grade ≥3 toxicity, and no contributions from IMRT. IMRT, which is meant to allow dose escalation, showed a reduction in grade ≥2 GI toxicity compared with 3D conformal RT in a study on 285 SRT patients. After a median follow-up of 60 months, the advantage of dose escalation regarding bNED and local control was not significant in the same patient cohort. Hypofractionated salvage IMRT (108 patients; median follow-up: 32.4 months) has been reported to induce 7% acute and 3% late GU toxicity grade ≥2. Acute GI tract reactions grade ≥2 occurred in 15 patients and late reactions in four patients. No grade ≥3 events were reported. The promising bNED results (67% at 4 years) await confirmation through longer follow-up. A retrospective analysis of 196 patients could show that bladder filling checks and image guidance can limit acute grade 3 GU toxicity after high-dose (76 Gy) IMRT to as low as 1–3%; grade 3 GI tract events were not observed in this study. Where reported, sexual function was frequently and severely impaired (range: 25–88%),[89,93–95] while the contribution of RT to this problem is low compared with the impact of surgery alone; in SWOG trial patients, the offset was less than 10% above the approximately 85% post-RP level with a slight recovery over 5 years in both therapy arms (the updated European Association of Urology guideline lists post-RP impotence as the most frequent side effect at 25–100%). During the same period, global health-related quality of life estimates deteriorated in RP-alone patients, but improved from 45 to 70% in ART patients. However, quality-of-life estimates should be regarded against the background of age-related health conditions (including comorbidity), of the status of being a cancer patient and in the post-RP setting of the side effects of surgery.[96,97]
Future Oncol. 2013;9(5):669-679. © 2013 Future Medicine Ltd.