Single fraction HDR brachytherapy offers the potential to effectively treat prostate cancer in a single outpatient treatment, with significant cost savings, efficient use of resources, and great patient convenience. Based on radiobiological considerations, and assuming a low alpha/beta ratio for prostate cancer, it was hypothesised that 19 Gy in a single fraction would have similar biological efficacy to fractionated treatments such as 27 Gy/2, 34.5 Gy/ 3, 39 Gy/4, or 45 Gy/6. Several investigators reported outcome following single 19 Gy. Treatment was universally well tolerated with a virtual absence of late gastro-intestinal toxicity, late grade 3 urinary toxicity rates typically under 5%, and high preservation of patient quality of life(1). Although early reports with median follow-up in the range of 18-36 months reported high disease control rates (2), longer follow-up was invariably associated with an unacceptably high recurrence rate, with failure-free survival rates typically of 66-75% in a mostly favourable risk population (3). A randomized trial of 19 Gy x 1 or 13.5 Gy x 2 in low and intermediate risk patients has reported a local failure rate of 29% and 3%, respectively, with a median follow-up of 5 years (4). It is uncertain whether increasing the prescription dose to 20.5 Gy leads to better results – failure free survival was still only 62% for patients with Gleason 7 disease at a median follow-up of just over 4 years (5).
Recurrence following single HDR predominantly occurs in the area of initial disease (6). This led investigators to explore further dose escalation to the initial dominant intraprostatic lesion using an MRI-guided focal boosting technique (7). Unfortunately, despite focal escalation of dose to over 27 Gy, local disease persistence was still common, with a local relapse rate of 32% in a series of low and intermediate risk patients(8). Focal boosting at time of single fraction HDR did not improve local control rates. This observation calls into question the underlying radiobiological assumptions, suggesting that factors such as hypoxia and tumour heterogeneity may limit the efficacy of single fraction treatments, even when given to extremely high dose.
Disease persistence or recurrence following single fraction HDR, however, is usually amenable to local salvage. Of 34 patients in our clinical trial who experienced local failure, 21 have undergone local salvage treatment – 13 (62%) with focal HDR, 6 (28%) with salvage prostatectomy and the others (10%) with focal ablative therapies (1).
In conclusion, single fraction HDR, even with focal dose escalation is associated with an unacceptably high local recurrence rate. This most often occurs at the site of initial bulk disease and is usually amenable to further local salvage treatment.
1. Corkum M, Loblaw A, Hasan Y et al.Morton G. Prostate high dose-rate brachytherapy as monotherapy for prostate cancer: Late toxicity and patient reported outcomes from a randomized phase II clinical trial. Radiother Oncol. 2021;156:160-165.
2. Hoskin P, Rojas A, Ostler P et al.Lowe G. Single-dose high-dose-rate brachytherapy compared to two and three fractions for locally advanced prostate cancer. Radiother Oncol. 2017;124(1):56-60.
3. Siddiqui ZA, Gustafson GS, Ye H et al.Krauss DJ. Five-Year Outcomes of a Single-Institution Prospective Trial of 19-Gy Single-Fraction High-Dose-Rate Brachytherapy for Low- and Intermediate-Risk Prostate Cancer. Int J Radiat Oncol Biol Phys. 2019;104(5):1038-1044.
4. Morton G, McGuffin M, Chung HT et al.Loblaw A. Prostate high dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: Efficacy results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy. Radiother Oncol. 2020;146:90-96.
5. Prada PJ, Ferri M, Cardenal J et al.Ruiz S. High-dose-rate interstitial brachytherapy as monotherapy in one fraction of 20.5 Gy for the treatment of localized prostate cancer: Toxicity and 6-year biochemical results. Brachytherapy. 2018;17(6):845-851.
6. Mendez LC, Ravi A, Chung H et al.Morton G. Pattern of relapse and dose received by the recurrent intraprostatic nodule in low- to intermediate-risk prostate cancer treated with single fraction 19 Gy high-dose-rate brachytherapy. Brachytherapy. 2018;17(2):291-297.
7. Alayed Y, D’Alimonte L, Helou J et al.Loblaw A. MRI assisted focal boost integrated with HDR monotherapy study in low and intermediate risk prostate cancer (MARS): Results from a phase II clinical trial. Radiother Oncol. 2019;141:144-148.
8. Alayed Y, Loblaw A, McGuffin M et al.Morton G. Single-fraction HDR brachytherapy as monotherapy in low and intermediate risk prostate cancer: Outcomes from two clinical trials with and without an MRI-guided boost. Radiother Oncol. 2020;154:29-35.