A prospective study of mr-assisted salvage hdr prostate brachytherapy with intra-prostatic boost

Purpose Because multiparametric MRI can generate detailed images of the anatomic extent of cancer within the prostate, its integration in salvage therapies such as brachytherapy has been widely embraced. It has enabled focal therapies and whole-gland therapies with intra-prostatic boost. The objectives of our prospective study is to investigate the efficacy and toxicities of MR-assisted whole-gland salvage HDR prostate brachytherapy with intra-prostatic boost in patients with local recurrent prostate cancer. Material and Methods Eligible patients included: multiparametric 3T MRI (mpMRI) visible biopsy confirmed local recurrence >30 months after XRT, negative metastatic workup, and IPSS <15. Ultrasound-based HDR brachytherapy with intraoperative contour-based deformable registration between the mpMRI and ultrasound images were done in 28 of 30 patients, and cognitive fusion in the remaining 2 patients. The prescription dose was 21Gy to the entire prostate and 27Gy to the MR-defined intraprostatic target volume (TV) divided over two implants separated by 1-2 weeks with dose constraints to the urethra and rectum. Adjuvant androgen deprivation therapy (ADT) was not used. Post-treatment response was evaluated using mpMRI 1-2 years after salvage. Follow-up PSA, IPSS and CTCAE v4.0 toxicities were collected. Results 30 patients (median age 74 years) were enrolled in the study. Median follow up from salvage HDR was 33 months (12-60). At initial presentation, there were 3, 18 and 9 low-, intermediate- and high-risk disease. The initial XRT dose was 70-78Gy with conventional fractionation in 28 patients and alternate fractionation in 2 patients (35Gy/5F and 50Gy/15F). Median time from initial treatment to biopsy-confirmed local recurrence was 9.3 years (2.4-17.6). The Gleason score of the local recurrence was 6, 7 and 8-10 in 2, 19 and 9, respectively. The pre-HDR median PSA was 3.67ng/mL (0.63-11.01). The median size of the prostate was 33.8 mL (15.9-86.0) and TV was 4.7mL (1.5-15.5). The median dosimetric endpoints per implant were: prostate V10.5Gy 96.5% (94.1-98.7), prostate D90 11.4Gy (10.9-12.0), TV V13.5Gy 94.2% (63.3-100), TV D90 18.1Gy (15.0-22.2), urethral D10% 12.0Gy (11.5-12.6), urethral Dmax 12.6Gy (12.2-13.5) and rectal V8.4Gy 0mL (0-0.8). Four patients (13%) required temporary urinary catheterization. There were no acute/late GU/GI grade 3-5 toxicities. The most common acute toxicity was frequency, dysuria and urgency. Mean IPSS at baseline, 1.5-, 3-, 6-, 9-, 12-, 18-, 24-, 30- and 36-months was 6, 15, 10, 11, 10, 12, 10, 10, 9 and 7, respectively (p=0.03). Three-year PSA progression-free survival and freedom from ADT rate was 67% and 93%, respectively. Of the 26 patients who had a post-HDR MRI (median 415 days), 18 (69%) patients had a complete response and 8 had persistent disease in the TV. No patients recurred elsewhere in the prostate. Conclusions Our toxicity, IPSS and PSA failure-free results suggests that whole gland salvage HDR brachytherapy with intra-prostatic boost is well tolerated and effective. Because multiparametric MRI can generate detailed images of the anatomic extent of cancer within the prostate, its integration in salvage therapies such as brachytherapy has been widely embraced. It has enabled focal therapies and whole-gland therapies with intra-prostatic boost. The objectives of our prospective study is to investigate the efficacy and toxicities of MR-assisted whole-gland salvage HDR prostate brachytherapy with intra-prostatic boost in patients with local recurrent prostate cancer. Eligible patients included: multiparametric 3T MRI (mpMRI) visible biopsy confirmed local recurrence >30 months after XRT, negative metastatic workup, and IPSS <15. Ultrasound-based HDR brachytherapy with intraoperative contour-based deformable registration between the mpMRI and ultrasound images were done in 28 of 30 patients, and cognitive fusion in the remaining 2 patients. The prescription dose was 21Gy to the entire prostate and 27Gy to the MR-defined intraprostatic target volume (TV) divided over two implants separated by 1-2 weeks with dose constraints to the urethra and rectum. Adjuvant androgen deprivation therapy (ADT) was not used. Post-treatment response was evaluated using mpMRI 1-2 years after salvage. Follow-up PSA, IPSS and CTCAE v4.0 toxicities were collected. 30 patients (median age 74 years) were enrolled in the study. Median follow up from salvage HDR was 33 months (12-60). At initial presentation, there were 3, 18 and 9 low-, intermediate- and high-risk disease. The initial XRT dose was 70-78Gy with conventional fractionation in 28 patients and alternate fractionation in 2 patients (35Gy/5F and 50Gy/15F). Median time from initial treatment to biopsy-confirmed local recurrence was 9.3 years (2.4-17.6). The Gleason score of the local recurrence was 6, 7 and 8-10 in 2, 19 and 9, respectively. The pre-HDR median PSA was 3.67ng/mL (0.63-11.01). The median size of the prostate was 33.8 mL (15.9-86.0) and TV was 4.7mL (1.5-15.5). The median dosimetric endpoints per implant were: prostate V10.5Gy 96.5% (94.1-98.7), prostate D90 11.4Gy (10.9-12.0), TV V13.5Gy 94.2% (63.3-100), TV D90 18.1Gy (15.0-22.2), urethral D10% 12.0Gy (11.5-12.6), urethral Dmax 12.6Gy (12.2-13.5) and rectal V8.4Gy 0mL (0-0.8). Four patients (13%) required temporary urinary catheterization. There were no acute/late GU/GI grade 3-5 toxicities. The most common acute toxicity was frequency, dysuria and urgency. Mean IPSS at baseline, 1.5-, 3-, 6-, 9-, 12-, 18-, 24-, 30- and 36-months was 6, 15, 10, 11, 10, 12, 10, 10, 9 and 7, respectively (p=0.03). Three-year PSA progression-free survival and freedom from ADT rate was 67% and 93%, respectively. Of the 26 patients who had a post-HDR MRI (median 415 days), 18 (69%) patients had a complete response and 8 had persistent disease in the TV. No patients recurred elsewhere in the prostate. Our toxicity, IPSS and PSA failure-free results suggests that whole gland salvage HDR brachytherapy with intra-prostatic boost is well tolerated and effective.