Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial

Abstract

BackgroundIncreasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment.Materials and MethodsWe conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival.ResultsBetween 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%.ConclusionsWeekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed.

Hypofractionated radiotherapy for localized prostate cancer

“…[47, 48]12930100 % intermediateRobotic IGRT40 Gy/5 fxNo ADTBRFS 94 % @ 4 yearsG 2 GU 10 %G 2 GI 2 %Menkarios et al. [49]8033100 % lowIMRT/IGRT45 Gy/5 fxBC 98 % @ 5 yearsG ≥ 2 GU 14 %G ≥ 2 GI 16 %Oliai et al. [50]703751 % low31 % intermediate17 % highRobotic IGRT35 Gy/5 fx36.3 Gy/5 fx37.5 Gy/5 fx33 % ADTFFBF 100 %/95 %/77 %G 3+ GU 3 %G 3+ GI 0 %Quon et al.…”

“…Late grade 2 toxicity rates from these individual institutional experiences vary significantly (1–31 %), with grade 4 toxicity occasionally reported [36, 37, 49]. While urinary incontinence is uncommon in conventional fractionation, in one study it was reported to be as high as 10 % in previously continent men 3 years post-SBRT [52].…”

A Systematic Review of Hypofractionation for Primary Management of Prostate Cancer

“…Late grade 2 toxicity rates from these individual institutional experiences vary significantly (1-31%), with occasional grade 4 toxicities reported [25,28,29]. While urinary incontinence is uncommon in conventional fractionation, in one study it was reported as high as 10% in previously continent men 3 yr post SBRT [30].…”

Hypofractionated radiotherapy in prostate cancer

“…However, with hypofractionation, there may be less time to allow normal tissues to recover. This can cause increased acute effects, thereby giving rise to more severe consequential late damage [16].…”