This article is more than 5 years old. Information may no longer be current.
Single-fraction, high-dose brachytherapy may be viable for localized prostate cancer
Click Here to Manage Email Alerts
Single-fraction 19 Gy high dose–rate brachytherapy may be a safe and effective treatment alternative for men with localized prostate cancer, according to study results published in International Journal of Radiation Oncology * Biology * Physics.
“It is becoming apparent that patients may be treated definitively for their prostate cancer in as little as a single day with a minimally invasive outpatient procedure,” Daniel J. Krauss, MD, radiation oncologist at Oakland University William Beaumont School of Medicine, said in a press release. “We found that patients generally can resume normal activities the following day with typical side effects.”
Brachytherapy historically has been administered as a low dose–rate procedure using radioactive seeds that remain inside the patient. High dose–rate (HDR) brachytherapy has been traditionally administered in four to nine treatment fractions, and it often requires multiple invasive procedures.
Krauss and colleagues conducted a prospective, nonrandomized trial to assess the safety and efficacy of single-dose 19-Gy HDR brachytherapy to the prostate among 58 patients with localized prostate cancer. Median patient age was 63 years, and 91% presented with stage T1 disease.
Within 6 months, 12.1% of patients experienced grade 2 urinary side effects and 6.9% experienced urinary frequency or urgency.
At median follow-up of 3 years, 10.3% of patients experienced chronic grade 2 urinary toxicity and 1.7% experienced grade 3 chronic gastrointestinal toxicity that later resolved.
HemOnc Today spoke with Krauss about the study and the potential impact of the findings.
Question: How did this study come about?
Answer: The study was an evolution of projects that started during the early 1990s. When we started doing HDR brachytherapy for prostate cancer, it was performed in high-risk patients in combination with external-beam radiation, which we still do now for cases of high-risk disease. Starting in the late 1990s, when brachytherapy was used by itself for patients with more favorable and intermediate-risk disease, it was done as a four-fraction process that was very involved. It included placing a transperineal implant and patients stayed in the hospital for 30 to 36 hours, during which time they received four fractions of HDR brachytherapy. When sufficient follow-up was available on the four-fraction patients, we increased the dose per fraction and began a protocol where we decreased from four fractions to two fractions. When we achieved sufficient follow-up on these patients demonstrating favorable safety and efficacy, we decreased to one fraction. Starting in 2010, we opened a 19-Gy single-fraction protocol with a goal of streamlining the treatment and making it easier for patients through decreased time commitment, decreased invasiveness and less exposure to anesthesia.
Q: How did you conduct this study?
A: The study was a prospective, nonrandomized trial. Patients were admittedly highly selected. These were men with no prior history of malignancies, they had good urinary function and low American Urological Association composite symptom scores, they could not have been on alpha-blocker medication for urinary symptoms prior to enrolling in the trial, and they all had either low- or intermediate-risk prostate cancer. Delivery of the procedure was very similar to what had been done previously in our department. Instead of putting patients through multiple procedures to treat their prostate cancers, now they only had to do one.
Q: What did you find?
A: Prostate cancer is completely treated in a single, minimally invasive procedure in which patients resume largely normal daily activities within 24 hours. I would consider this conclusive. The toxicity rates were extremely low. No significant complications have been observed. However, we cannot say conclusively whether 19 Gy in a single fraction works as well as the multifraction regimens because of the time required to follow people with favorable prostate cancer. The natural history of the disease is so long that it will take longer than 3 years of follow-up to make this determination. Still, we are certainly very encouraged by these initial data, and if the trends we have seen to this point hold, we hope this eventually will be a standard treatment option we can offer appropriate patients with low- and intermediate-risk prostate cancer.
Q: Can you describe the potential impact of the findings?
A: The main drawback of HDR brachytherapy relative to low dose–rate — or permanent-seed — brachytherapy is that there are challenges with the workflow of the procedure, such as giving multiple fractions and the multiple exposures to anesthesia. By giving everything in a single-fraction, we essentially eliminate many of those challenges and, at the same time, make it an easier, less risky and more convenient process for the patient. Although we would never compromise treatment quality for cost, another potential advantage of this approach is that the cost of giving a treatment in a single fraction is substantially less than giving it in multiple fractions.
Q: What will future research entail?
A: One of the nuances of HDR brachytherapy is that the fewer fractions you go to — from four down to two, or from two down to one — the more critical the biological assumption of the dose selection becomes. Although there is sound biological justification for the 19-Gy single-fraction dose, I do not think we can simply assume it is optimal. Given that the toxicity was so low in this study, we have a protocol open now continuing with our single-fraction HDR research, and we have increased the dose on our current protocol to 21 Gy. That protocol is accruing. Beyond that, we hope to take it into a multi-institutional type of setting. In my opinion, this is what HDR brachytherapy needs at this point, such that we can demonstrate that the results are consistent and reproducible across multiple centers.
Q: What is the timeline for this future research?
A: I would hope to complete accrual on the next phase of the protocol — 21 Gy in a single fraction — within the next 6 to 12 months. It likely will be an additional 1 to 2 years for adequate follow-up to allow for comparison with the patients who received 19 Gy. However, we should have toxicity and preliminary data sooner than this. Hopefully within the next year we will be able to report preliminarily on how well patients are tolerating the treatment.
Q: Is there anything else that you would like to mention for our readers?
A: HDR brachytherapy delivered in definitive fashion is an excellent treatment option for appropriately selected patients with localized prostate cancer. Such patients tolerate the treatment well with a highly favorable side effect profile. In the vast majority of cases, they are able to resume normal activity levels almost immediately following treatment completion. The single fraction option offers a simplification of the workflow and treatment process that should make it more attractive to both patients and clinicians. Multifraction HDR treatment remains a standard option, but due to the relatively short follow-up interval, single-fraction treatment remains investigational and should not be offered to patients outside the context of clinical trials. – by Jennifer Southall
Reference:
Krauss DJ, et al. Int J Rad Oncol Biol Phys. 2017;doi:10.1016/j.ijrobp.2016.08.011.
For more information:
Daniel J. Krauss, MD, can be reached at Oakland University William Beaumont School of Medicine, 2200 N. Squirrel Road, Rochester, MI 48309; email: dkrauss@beumont.edu.
Disclosure: Krauss reports no relevant financial disclosures.