Eighth randomized clinical trial of hypofractionated radiation therapy

We now have an eighth randomized clinical trial of hypofractionated radiation therapy. There are no surprises: it showed that oncological and toxicity outcomes were not significantly different between the two regimens. We last looked at it here. This trial is unusual because of the length of follow-up.

Arcangeli et al. report the 10-year outcomes of their study covering 168 high risk patients treated using 3D-CRT (not IMRT) at the Regina Elena Cancer Institute in Rome between 2003 and 2007. The details of the treatments were as follows:

• Half (85 patients) received conventionally fractionated (Conv)  80 Gy in 40 fractions
• Half (83 patients) received hypofractionated (Hypo) 62 Gy in 20 fractions

After a median of 9 years of follow-up:

• 10-year freedom from biochemical failure was 72% for the Hypo group vs. 65% for the Conv group.(no statistically significant difference)
• 10-year prostate cancer -specific survival was 95% for the Hypo group vs. 88% for the Conv group (no statistically significant difference)
• 10-year overall survival was 75% for the Hypo group vs. 64% for the Conv group (no statistically significant difference)
• Hypofractionation was a significant variable in determining prostate cancer-specific survival in multivariate analysis
• There were no differences in late-term grade 2 or higher urinary or rectal toxicity between the 2 groups.

There are a couple of caveats. For those who insist on rigorous analysis, the Hypo group had worse oncological and toxicity outcomes on an intention-to-treat basis. It was only after the patients were analyzed according to the treatment they actually received that the lack of statistically significant difference became apparent. James Yu, in an accompanying editorial, points out that blood in urine was 16.5% for the Hypo group vs. 3.6% for the Conv group. This may be a caution that hypofractionation should not be attempted using 3D-CRT. In the US, where IMRT is widely available, this should not be an issue.

Here's the table summarizing all 8 randomized clinical trials:

Randomized Clinical Trial	Risk Groups	Fractionation	5-yr bPFS	Urinary toxicity Grade 2+	Rectal toxicity Grade 2+	Ref.
PROFIT	100% intermediate	60 Gy/20fx 78 Gy/39fx	85% 85%	22% 21%	8% 14%	1
Fox Chase	67% Intermediate, 33% high	70.2 Gy/26fx 76 Gy/38fx	77% 79%	22% 13%	18% 23%	2
CHHiP	73% intermediate, 15% low, 12% high	60 Gy/20fx 74 Gy/37fx	91% 88%	12% 9%	12% 14%	3
MD Anderson	71% intermediate, 28% low, 1% high	72 Gy/30fx 75.6 Gy/42fx	89%† 85%†	16% 17%	10% 5%	4
RTOG 0415	100% low risk	70 Gy/28fx 73.8 Gy/41fx	94% 92%	30% 23%	22% 14%	5
HYPRO	>70% high, <30% intermediate	64.6 Gy/19fx 78 Gy/39fx	81% 77%	41% 39%	22% 18%	6, 7
Cleveland Clinic	49% low, 51% intermediate	70 Gy/28fx 78 Gy/39fx	94% 88%	1% 2%	5% 12%	8
Regina Elena	100% high risk	62 Gy/20 fx 80 Gy/40 fx	72%* 65%*	21% 14%	NA NA	9

*10-year figures for the Regina Elena trial
† 8-yr failure-free survival update for MD Anderson