Hyaluronic Acid Spacer in Prostate Cancer Radiotherapy: Dosimetric Effects, Spacer Stability and Long-Term GI Toxicity and PRO in a Phase II-Study

Abstract

<h3>Purpose/Objective(s)</h3> Rectal side effects are common after radiotherapy (RT) to the prostate. To reduce side effects, perirectal spacers to separate the prostate from the rectum, thereby reducing the rectal dose, may be beneficial. This study presents the impact of a hyaluronic acid (HA) perirectal spacer on the rectal dose, MRI evaluation of spacer thickness during RT and a five-year follow-up of patient-reported outcome (PRO) and gastrointestinal (GI) toxicity. <h3>Materials/Methods</h3> 81 patients (<75 years) with low- (T1c-T2 and Gleason ≤ 6 and PSA < 10) and intermediate-risk prostate cancer (PC) (T1c-T3a with 1 or 2 of the risk factors T2c-T3a or Gleason ≥ 7 or PSA ≥ 10) received transrectal injections with HA (Macrolane VRF 30, Q-Med/Galderma, Uppsala, Sweden) as a perirectal spacer in this phase II-study between 2010-2016. External beam RT, 78 Gy in 39 fractions, were given with 3DCRT or IMRT using fiducial markers as image guidance. MRI was performed before (MR0) and after HA injection (MR1), at the middle (MR2) and at the end of RT (MR3). GI toxicity was assessed up to five years according to the RTOG scale. PRO GI side effects were collected using The Swedish national prostate cancer registry (NPCR) and PCSS questionnaires. <h3>Results</h3> HA thickness was measured at the prostate base, middle and apex for 52 of 81 patients. Exclusion due to failed HA-injections (6), missing MRT or RT data (17), larger PTV margins (5) and other treatment (1). HA thickness and CTV-Rectum spaces in apex- and middle- position was decreasing from MR1 to MR2/MR3. No significant differences were found between MR2 and MR3. Overall, HA thickness in the middle position had the strongest significant correlation (Spearman's rho ρ= 0.70) to CTV-Rectum spacing. There was a significant decrease in the relative rectum volume that received 70.2 Gy (V90%) from MR0 (8.6 ±5.7 %) to MR1 (2.7± 4.1 %). There was a significant increase from MR1 to MR2 (6.0±9.0%) and no significant difference between MR2 and MR3 (5.7±7.9 %) in rectum V90%. All with significance p<0.05. At the end of RT 17 patients (25.8%) experienced grade 1 GI toxicity, and four patients (6.1%) grade 2. At six months the proportion of grade 2 and 3 GI toxicity was 3.2%, and 1.6%. After 18 months no grade ≥ 2 GI toxicity was observed. The estimated cumulative late grade ≥ 2 GI toxicity rate at 5 years was 4.8 %. PRO moderate or severe overall bowel problems at start RT, end of RT and 5 years were 0%, 17.6% and 12.2% with a mean score of 14.6 (scale 0–100; higher value refers to more symptoms/worse function) at 5 years. <h3>Conclusion</h3> After HA-spacer, the relative rectum volumes receiving 70.2 Gy (V90%) were significantly lower. V90% increased significantly from MR1 to MR2/MR3, but still a significant reduction from MR0. The 5-year cumulative risk of late GI toxicity grade >1 was low whereas 12 % reported moderate/severe GI-bothers in the PRO at 5 years.