Prostate hypofractionated radiotherapy (62Gy at 3.1Gy per fraction) with injection of hyaluronic acid: final results of the RPAH1 study

Abstract

Objectives: The present multicenter Phase II study evaluated the rate of late grade ≥2 gastrointestinal (GI) toxicities at 3 years, after hypofractionated radiotherapy (HFR) of prostate cancer with injection of hyaluronic acid (HA) between the prostate and the rectum. Methods: Between 2010 and 2013, 36 patients with low- or intermediate-risk prostate cancer were treated by HFR/IMRT-IGRT. 20 fractions of 3.1 Gy were delivered, 5 days per week for a total dose of 62 Gy. A transperineal injection of 10cc of HA was performed between the rectum and the prostate. Late toxicities were evaluated between 3 and 36 months after the end of treatment (CTCAE v4). Results: Median pretreatment prostate-specific antigen was 8 ng ml−1. Among the 36 included patients, 2 were not evaluated because they withdrew the study in the first 3 months of follow-up, and 4 withdrew between 3 and 36 months, the per protocol population was therefore composed. Late grade ≥2 GI toxicities occurred in 4 (12%) patients with 3 (9%) Grade 2 rectal bleedings and one diarrhoea. Therefore, the inefficacy hypothesis following Fleming one-stage design cannot be rejected. None of the patients experienced late Grade 3–4 toxicities. Among the 30 patients completing the 36 months’ visit, none still had a grade ≥2 GI toxicity. Late grade ≥2 genitourinary (GU) toxicities occurred in 14 (41%) patients. The most frequent toxicities were dysuria and pollakiuria. Four patients still experienced a grade ≥2 GU toxicity at 36 months. The biochemical relapse rate (nadir +2 ng ml−1) was 6% (2 patients). Overall, HA was very well tolerated with no pain or discomfort. Conclusion: Despite the inefficacy of HA injection was not rejected, we observed the absence of Grade 3 or 4 rectal toxicity as well as a rate of Grade 2 rectal bleeding below 10% at 36 months of follow-up. Late urinary toxicities are the most frequent but the rate decreases largely at 3 years. Advances in knowledge: With an injection of HA, hypofractionated irradiation in 4 weeks is well tolerated with no Grade 3 or 4 GI toxicity and a rate of Grade 2 rectal bleeding below 10% at 36 months of follow-up.

Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy

“…Further follow-up is needed to characterize the long-term toxic effects and QOL outcomes with the HA spacer. We will test whether the decreased rectal dose, which led to reduced acute grade 2 or higher toxic effects in this study, will ultimately lead to improved bowel QOL at 3 years.…”

Hypofractionated Radiotherapy in Localized, Low–Intermediate-Risk Prostate Cancer: Current and Future Prospectives

“…The RPAH1 (hyaluronic acid for hypofractionated prostate radiotherapy) non-randomized, phase II study examined grade ≥ 2 GI late toxicity rates at 3 years after hypofractionated radiotherapy (62 Gy at 3.1 Gy per fraction) in patients who received a hyaluronic acid injection between the prostate and rectum. No grade 3 or 4 rectal toxicities were observed, the grade 2 rectal bleeding rate was less than 10% at 36-month FU and the 3-year late urinary toxicities were decreased [ 35 ].…”

Comprehensive review of the use of hydrogel spacers prior to radiation therapy for prostate cancer

“…A single‐arm study evaluated the use of spacers with hypofractionated radiation therapy (62 Gy in 20 fractions) in 36 patients between 2010 and 2013. In that study, there were four (12%) Grade 2 rectal toxicities (three rectal bleeding and one diarrhoea), with no Grade 3 and above rectal toxicities [49]. Only one study evaluated rectal toxicity with the use of a spacer in men treated with SBRT (36.25 Gy in five fractions).…”

“…The aim of hydrogel spacer insertion is to increase spatial separation between the prostate and rectum with the intention of reducing rectal dosimetry during radiation therapy in the hope that this will translate into reduced patient-reported symptoms of rectal toxicity. However, it is important to consider the type of radiation therapy technique (i.e., external beam radiation therapy alone [23,[38][39][40][41], brachytherapy alone [29, [42][43][44][45], or external beam radiation therapy in combination brachytherapy boost [29, [44][45][46], or proton beam radiation therapy [47]) as well as the dose fractionation [48,49] used when evaluating these outcomes.…”