The value of randomised trials for prostate cancer management
Mené sur 843 patients atteints d'un cancer de la prostate de stade T1b-T3aN0M0 traité entre 1998 et 2001 (durée médiane de suivi : 10 ans ; taux du PSA au diagnostic < 50 ng/mL), cet essai international de phase III évalue, du point de vue de la survie sans progression biochimique et de la survie globale à 10 ans, l'efficacité d'une radiothérapie conformationnelle avec escalade de dose en combinaison avec un traitement néoadjuvant anti-androgénique
In The Lancet Oncology, David Dearnley and colleagues1 report the long-term outcomes of the Medical Research Council (MRC) RT01 study—a randomised study of 64 Gy versus 74 Gy of conformal radiotherapy given with 3—6 months of neoadjuvant or concomitant androgen deprivation therapy (ADT). The authors are to be commended for completing and successfully managing this high quality trial over the past 20 years. As they rightly point out, this is one of six randomised trials that have examined the possible benefits of dose escalation for external beam radiotherapy. In sum, an additional week of radiotherapy improves biochemical control by about 18%.2 In this trial with 843 participants, the 10-year absolute difference in biochemical progression-free survival was 12% (43% [95% CI 38—48] in the standard-dose group vs 55% [50—61]; hazard ratio [HR] 0·69 [95% CI 0·56—0·84]; p<0·0001) with no significant difference in overall survival (71% [95% CI 66—75] in both groups; HR 0·99 [95% CI 0·77—1·28]; p=0·96).
Although overall survival is the gold-standard outcome to improve, it is exceptionally difficult to show in localised disease diagnosed in a screen-detected era when median overall survival approaches 20 years. This difficulty is particularly evident when technological advances introduce supposedly better techniques every 2—5 years. Notably, the SWOG 8794 study3 did not show an overall survival advantage when it reported its 10·6 year median follow-up results, despite having a high-risk postoperative population, and doing the trial early in the prostate-specific antigen (PSA) screening era. Although PSA recurrence is not a perfect surrogate for overall survival, clinical experience suggests that higher PSA control means that more patients feel good about their disease status, and are free of next-line treatment interventions with their attendant side-effects and costs...
The Lancet Oncology , commentaire en libre accès, 2013