ASTRO 2021: Advances in Prostate Brachytherapy

(UroToday.com) In an educational session at the American Society for Radiation Oncology (ASTRO) Annual Congress focused on the best treatment for early prostate cancer, Dr. Morton presented on advances in prostate brachytherapy.

Dr. Morton began by emphasizing the NCCN clinical guidelines in oncology for prostate cancer recommend brachytherapy and EBRT as both appropriate treatment options for patients with favourable intermediate risk disease.

He then emphasized that brachytherapy comes in two “flavours”, low dose rate (LDR) or permanent seed implant and high dose rate (HDR). He described brachytherapy as the most elegant way to administer radiotherapy to prostate tumors. Dr. Morton then discussed both physics and radiobiology based rationale for the use of brachytherapy. From a physics perspective, brachytherapy allows the highest possible dose to the tumor with a lower dose to the rectum and bladder with the least integral dose (and thus lower risks of long-term secondary malignancies) and the ability for intraprostatic dose painting. From a radiobiology perspective, it has favourable dose rate effects and alpha/beta considerations.

Considering dose distributions, Dr. Morton emphasized that both LDR and HDR brachytherapy compare favourably to SBRT in terms of the ability to provide conformality and OR dose with rapid dose fall-off. 

Prospective results among men with intermediate risk prostate cancer demonstrated a median nadir PSA of 0.01 with five-year biochemical failure free survival of 97%. However, he emphasized that the problem with LDR brachytherapy is the associated urinary toxicity, both with immediate acute effects (peaking around 1 month) and also persistent long-term effects.

Building on this, the question arose whether HDR brachytherapy monotherapy could provide the same cancer control with a more favourable toxicity profile. Dr. Hathout and colleagues performed a randomized comparison among patients with low and intermediate risk disease, finding that HDR monotherapy had lower peak IPSS scores and higher mean EPIC urinary irritative scores following treatment, suggesting in fact that this was true.

Considering next the oncologic control associated with HDR monotherapy, Dr. Morton highlighted a number of trials of fractionated HDR brachytherapy which have together shown favourable biochemical disease-free survival rates over median follow-up ranging from 3 to nearly 8 years.

Many of these studies used up to 9 fractions. The question has arisen whether this may be decreased, potentially down to one fraction of 19 Gy. Based on radiobiologic considerations, he suggested that this would be equivalent (in terms of BED and EQD2) to alternatively employed fractionation strategies.

At Sunnybrook, they undertook a randomized controlled trial of single fraction HDR monotherapy (19 Gy) versus two fraction (13.5 Gy) HDR monotherapy one week apart. In total, 170 patients with predominately intermediate risk disease were accrued and randomized with follow-up now exceeding 6 years. First, the authors found that GI toxicity was minimal with both approaches. However, GU toxicity was more common though it did not meaningfully differ between the two groups. Grade 3 GU toxicity, while rare, was only observed in the single fraction group. Unfortunately, the single fraction approach demonstrated significantly worse efficacy: PSA relapse free survival rates were much lower (74% vs 95%, p=0.0011) and local failure rates were 10x higher (30% vs 3%, p<0.0001). As a result, this approach cannot be recommended. Instead, two fraction HDR (27 Gy in 2 fractions) should be preferred with low toxicity, excellent preservation of health related quality of life, and disease control rates similar to LDR.

The question however is can we do better. Use of mpMRI may allow focal boost, which is particularly amenable to an HDR approach. Further PSMA-PET/CT (as well as mpMRI) may be fused with TRUS at the time of implantation to allow for localization. Interestingly, Dr. Morton noted that focal boosting of tumor foci is not associated with any increase in toxicity or detriments to health related quality of life.

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting, Sat, Oct 23 – Wed, Oct 27, 2021.