Aim: To update results of a trial comparing conventionally fractionated (80 Gy/40 fxs/8

wks)(CF) vs hypofractionated (62 Gy/20 fxs/5 wks)(HYPO) 3DCRT for high-risk prostate
cancer. The study aimed at comparing morbidity, while the two schedules were assumed to
be isoeffective on tumor control for an ratio of 1.5 Gy and disregarding the time factor
[1,2].
Methods and Materials: This randomized phase III trial was run at a single Institution from
2002 to 2005 and included 9-month androgen deprivation therapy in both arms. The target
consisted in both the prostate and seminal vesicles. Freedom from biochemical failure
(FFBF) (Phoenix), freedom from distant metastases (FFDM) and prostate cancer specific
survival (PCSS) are reported after a median follow up of 96.5 months (6.2-130.8) for living
patients.
Results: 168 patients were accrued. The two arms are slightly unbalanced in favor of CF with
respect to initial PSA (iPSA) level, Mann Whitney U test p=0.17. Overall, 8-yr FFBF is
74.2+3.8%, 66.0+5.9% for CF and 82.0+4.7% for HYPO, p=0.058. At multivariate analysis,
treatment arm (CF vs HYPO, HR=0.40, 95%CI: 0.20-0.79, p=0.009), Gleason Score (GLS)(cont,
p=0.001) and iPSA (cont, p<0.001) were independently correlated to biochemical failure.
Only 20 patients developed distant metastases for an actuarial rate for FFDM of 88.1+2.6%
at 8 yrs. Patients treated with HYPO had a slightly higher rate of distant control at 8 yrs,
91.6+3.3% vs 84.9+4.0%, but neither at univariate or multivariate analyses the difference
reached statistical significance (p=0.321 and p=0.199, respectively). Of note, the HR of
distant failure is 0.55 (95%CI: 0.22 to 1.36) in favor of HYPO over CF. Both iPSA and GLS were
highly correlated to FFDM, p=0.004 and p<0.001, respectively.
Out of 42 observed deaths, only 10 were due to prostate cancer-related causes. Overall,
PCSS at 8 yrs is 92.8+2.2%. Eight-yr PCSS is 89.0+3.7% and 96.7+2.3% for CF and HYPO,
respectively, HR=0.24, 95%CI=0.05-1.12, p=0.07. At multivariate analysis, only GLS (p=0.037)
reached statistical significance, while a trend was confirmed for treatment arm (HR=0.23,
95%CI: 0.05-1.10, p=0.068).
Discussion and Conclusions: Despite the limited sample size and the lack of radiobiological
expectations on tumor control, HYPO resulted in a statistically higher biochemical control
over CF, that tends to lead to a lower likelihood of both distant disease and prostate-cancer
death.
References:
1) Arcangeli G., Saracino B., Gomellini S. et al.: A prospective phase III randomized trial of
hypofractionation versus conventional fractionation in patients with high-risk prostate
cancer. Int J Radiat Oncol Biol Phys 2010;78:11-8
2) Arcangeli G., Fowler J., Gomellini S. et al.: Acute and late toxicity in a randomized trial of
conventional versus hypofractionated three-dimensional conformal radiotherapy for
prostate cancer. Int J Radiat Oncol Biol Phys 2011;79:1013-21