Dose Escalation for Prostate Adenocarcinoma: A Long-Term Update on the Outcomes of a Phase III, Single Institution Randomized Clinical Trial
Mené sur 301 patients atteints d'un adénocarcinome de la prostate de stade T1b-T3 (durée médiane de suivi : 14,3 ans), cet essai de phase III évalue, du point de vue de la réduction de l'échec biochimique et/ou de l'échec clinique à 15 ans, l'efficacité d'une radiothérapie avec escalade de doses
Objective : To determine the long-term outcomes for prostate adenocarcinoma when escalating radiation dose from 70 Gy to 78 Gy. Methods : Between 1993 and 1998, 301 patients with biopsy-proven clinical stage T1b – T3 prostate adenocarcinoma, any prostate-specific antigen (PSA) level, and any Gleason score were randomized to 70 Gy in 35 fractions vs. 78 Gy in 39 fractions photon radiation therapy using a four-field box technique without hormone deprivation therapy. The primary outcome was powered to detect a 15% difference in biochemical and/or clinical failure. Secondary outcomes included survival, prostate cancer mortality, biochemical failure, local failure, nodal failure, distant failure, and secondary malignancy rates. Results : With a median follow-up of 14.3 years, the cumulative incidence of 15-year biochemical and/or clinical failure was 18.9% vs. 12.0% in the 70-Gy vs. 78-Gy arm, respectively (sHR 0.61, 95% CI 0.38 – 0.98; Fine-Gray P=0.042). The 15-year cumulative incidence of distant metastasis was 3.4% vs. 1.1%, respectively (sHR 0.33, 95% CI 0.13 – 0.82; Fine-Gray P=0.018). The 15-year cumulative incidence of prostate cancer-specific mortality was 6.2% vs. 3.2%, respectively (sHR 0.52, 95% CI 0.27 – 0.98; Fine-Gray P=0.045). There were no differences in overall survival (HR 1.10, 95% CI 0.84-1.45; Log Rank P=0.469) or other-cause survival (sHR 1.33, 95% CI 0.99 – 1.79; Fine-Gray P=0.061). Salvage therapy was more common in the 70-Gy arm at 38.7% vs. 21.9% in the 78-Gy arm (P=0.002). There was a 2.3% secondary solid malignancy rate (1 bladder, 6 rectal) within the radiation treatment field which was not significantly different between treatment arms. Conclusion : Dose escalation by 8 Gy (78 Gy versus 70 Gy) provided a sustained improvement in biochemical and clinical failure which translated into lower salvage rates and improved prostate cancer-specific mortality but not overall survival. Long-term follow-up demonstrated a low incidence of potential solid tumor secondary malignancies.