High-dose-rate (HDR) brachytherapy administered in a single, 19 Gray (Gy) treatment may be a safe and effective alternative to longer courses of HDR treatment for men with localised prostate cancer, indicates a prospective clinical trial.
With brachytherapy, also known as internal radiation therapy (RT), implants are surgically inserted in or near cancerous tissue to deliver a curative radiation dose directly to the tumor while limiting exposure for surrounding healthy tissue. Reducing this exposure is of particular concern for treating tumors in the prostate, which is surrounded by multiple critical structures. In contrast to low-dose-rate (LDR) brachytherapy, where radioactive seed implants are placed permanently in the body and gradually deposit low levels of radiation over a period of months, HDR treatments deposit the dose in one treatment, after which the radioactive implant is removed from the patient.
Typically, HDR brachytherapy is administered in four to as many as nine treatment sessions, which generally requires multiple invasive procedures to insert the implants. While the number of sessions can be streamlined by increasing the dose given in each session, data on the safety and tolerability of highly escalated brachytherapy doses are still relatively new and therefore limited. In this study, researchers found that patients who received a single fraction of 19 Gy HDR brachytherapy experienced similar clinical outcomes as with LDR brachytherapy, but with the convenience of a single visit.
“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,” said lead study author Dr Daniel J Krauss, a radiation oncologist at Oakland University’s William Beaumont School of Medicine in Royal Oak, Michigan. “We found that patients generally can resume normal activities the following day with typical side effects.”
The study presented the results of a non-randomised, prospective clinical trial of 58 patients with low- or intermediate-risk (non-metastatic) prostate cancer, with a median follow-up period of 2.9 years. All patients received a single, 19 Gy fraction of HDR brachytherapy. The median patient age was 63 years (range 43-73), and 91% of the patients presented with stage T1 disease.
At an average of nearly three years following treatment, cancer control rates were favourable and the toxicity profile was highly favourable. Three patients experienced recurrence or progression, yielding an estimated three-year cumulative biochemical control rate of 93%. Within the six months following HDR therapy, seven patients (12.1%) experienced grade 2 urinary side effects, most commonly frequency/urgency (6.9%). No patients experienced short-term grade 3+ urinary toxicity or grade 2+ gastrointestinal (GI) toxicity. Rates were similarly modest for long-term side effects. Six patients (10.3%) experienced chronic grade 2 urinary toxicity and one patient (1.7%) experienced grade 3 chronic GI toxicity that subsequently resolved. No patients experienced long-term grade 3+ urinary toxicity or grade 4 GI toxicity.
“This study illustrates that a potentially curative dose of radiation may be delivered safely to the prostate entirely in a single administration,” said Krauss. “Giving the entire dose in a single treatment theoretically could have had a greater negative impact on the normal tissues in close proximity to the prostate – meaning the bladder, urethra and rectum – but this was not found to be the case. Toxicity rates were extremely low, with essentially no major complications encountered in this initial group of 58 patients.”
While findings highlight the potential tolerability of a single fraction of HDR brachytherapy for localised prostate cancer, the article also emphasises the need for additional follow-up to compare long-term cancer control rates with conventional treatment approaches, which generally administer larger cumulative doses than the 19 Gy dose used in this trial.
“As the follow-up interval lengthens, 19 Gy dosing in a single fraction may or may not be sufficient to result in cure rates comparable to historical standards. One thing that this study has made clear, however, is that the extremely low toxicity and complication rates leave room to escalate the single fraction dose in subsequent trials,” said Krauss. “While additional study and longer follow-up are necessary to confirm the optimal dose for single-fraction HDR brachytherapy, we are optimistic that the single-treatment approach can eventually become a standard practice for prostate cancer treatment.”
Purpose: To report the toxicity and preliminary clinical outcomes of a prospective trial evaluating 19-Gy, single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer.
Methods and Materials: A total of 63 patients were treated according to an institutional review board-approved prospective study of single-fraction HDR brachytherapy. Eligible patients had tumor stage ≤T2a, prostate-specific antigen level ≤15 ng/mL, and Gleason score ≤7. Patients with a prostate gland volume >50 cm3 and baseline American Urologic Association symptom score >12 were ineligible. Patients underwent transrectal ultrasound-guided transperineal implantation of the prostate, followed by single-fraction HDR brachytherapy. Treatment was delivered using 192Ir to a dose of 19 Gy prescribed to the prostate, with no additional margin applied.
Results: Of the 63 patients, 58 had data available for analysis. Five patients had withdrawn consent during the follow-up period. The median follow-up period was 2.9 years (range 0.3-5.2). The median age was 61.4 years. The median gland volume at treatment was 34.8 cm3. Of the 58 patients, 91% had T1 disease, 71% had Gleason score ≤6 (29% with Gleason score 7), and the median pretreatment prostate-specific antigen level was 5.1 ng/mL. The acute and chronic grade 2 genitourinary toxicity incidence was 12.1% and 10.3%, respectively. No grade 3 urinary toxicity occurred. No patients experienced acute rectal toxicity grade ≥2, and 2 experienced grade ≥2 chronic gastrointestinal toxicity. Three patients experienced biochemical failure, yielding a 3-year cumulative incidence estimate of 6.8%.
Conclusions: Single-fraction HDR brachytherapy is well-tolerated, with favorable preliminary biochemical and clinical disease control rates.
Daniel J Krauss, Hong Ye, Alvaro A Martinez, Beth Mitchell, Evelyn Sebastian, Amy Limbacher, Gary S Gustafson