Low-dose-rate brachytherapy may be effective in some prostate cancers

Derek Raghavan, MD, PhD, FACP, FRACP

I’m never very keen on papers that finish with self-congratulatory phrases, such as “these results were achieved in a nonfee-for-service, universal access medical environment in which multiple practitioners receive specific training; adhere to consistent, evidence-based eligibility criteria; and apply uniform, but evolving, treatment protocols…” As a result, I thought about the results from Morris and colleagues in a relatively negative fashion ab initio, and wondered why this worthy and well-trained group would treat more than 1,000 patients in an investigational but non-randomized fashion.

In general our colleagues north of the US-Canadian border have been exemplars of rational thinking and structured innovation, influenced by Tannock, Moore, Klotz, Gleave and many others. Yet this group began this huge “phase 2” program with very little data to support the use of ADT in this specific patient population. I do understand the concept of phase 2 testing, and generally agree with conventional wisdom that suggests that efficacy and toxicity can be defined in a group of fewer than 100 cases, and that subsequent development requires comparison against a standard of care. While their failure rates are very low, and thus impressive at first glance, one could reasonably question whether they used brachytherapy for a population that included a cohort with disease that didn’t actually require treatment at all, and ADT for a cohort who might actually have been harmed by it. I think that they compounded the felony by linking two unproven approaches. When progress was made in chemotherapy for metastatic testicular cancer, a randomized trial of the PVB regimen against cisplatin or vinblastine-bleomycin was not required as the difference in cure rates was dramatic.

In the present setting, the benefits of this regimen are unclear, and patients might have been harmed. Having a pre-determined treatment algorithm for an institution is a good concept, but it really should be driven by level 1 evidence, and shouldn’t be used as a surrogate for well-structured, comparative clinical research when trying to achieve improved outcomes.

William W. Wong, MD

This is a study that adds to the existing literature showing the excellent efficacy of LDR brachytherapy for low- and intermediate-risk prostate cancer. This study included a large number of patients who were treated in a uniform manner in a universal access, non-fee-for-service model of health care delivery. The formal training and certification program for radiation oncologists, as well as the large volume of patients in each center, undoubtedly contributed to the high quality of the brachytherapy and the excellent outcome. LDR brachytherapy costs much less than external beam radiation therapy.

On analysis of the prognostic factors, the use of short-term androgen deprivation therapy appeared to compensate for lower D90 and V100. For practitioners that perform LDR brachytherapy infrequently and may have concern whether they can achieve the prescribed dose coverage of prostate, the addition of short-term androgen deprivation therapy to the procedure would be a reasonable consideration. As mentioned in the discussion by the authors, 30% of their cohort would meet the criteria for active surveillance. Although LDR brachytherapy provides good disease control, many of these patients with low risk disease may not benefit from any treatment at all. The radiation oncologist is obligated to consult these patients fully on all options, including active surveillance.