Long-term survival after low-dose-rate brachytherapy for prostate cancer: the Royal Surrey experience.

OBJECTIVES: To assess the long-term treatment efficacy of low-dose-rate (LDR) brachytherapy for the treatment of localized prostate cancer. PATIENTS AND METHODS: Cause-of-death annotation in our prospective database was supplemented with death certificate information obtained via an internal audit of patients treated from 1999 to 2017 with LDR prostate brachytherapy as monotherapy or as combination with androgen deprivation therapy and/or external beam radiotherapy. Overall and disease-specific survival were the primary outcomes, estimated with Kaplan-Meier and competing risks multi-state models. Clinical variables influencing mortality were assessed with Cox proportional hazards regression in a sub-analysis of men to assess the predictive value of prostate-specific antigen (PSA) level at 48 months post implant. RESULTS: The audit process began in October 2017 and culminated in June 2020 with a curated series of 2936 patients. All-cause and prostate cancer-specific death prevalence were 11% and 2.9%, respectively. The median (range) follow-up time was 10 (3-21) years and the median (range) time to death from any cause was 9 (3-21) years. At 15 years post implant the overall and prostate cancer-specific survival probability were 81% and 95%, respectively. The 15-year cumulative incidence rates of death not due and due to prostate cancer were 14% and 5%, respectively. A greater risk of death due to prostate cancer was conferred by increasing age at therapy (hazard ratio [HR] 1.1, P < 0.001), advanced clinical stages relative to T1a-T2a (HR 1.9, P = 0.048 for T2b; HR 2.7, P = 0.023 for T2c-T3b) and a 48-month PSA level >1.0 ng/mL (HR 6.8, P < 0.001). CONCLUSION: This study constitutes the largest retrospective analyses of long-term mortality outcomes from prospectively collected prostate brachytherapy data and confirms the excellent treatment efficacy of LDR prostate brachytherapy for localized prostate cancer. T2 clinical stage subdivisions and 48-month PSA level >1.0 ng/mL appear to be strong indicators of prostate cancer-related survival.

Robot-assisted salvage seminal vesicle excision for isolated recurrence after low-dose-rate prostate brachytherapy.

OBJECTIVES: To report clinical and functional outcomes for patients who have undergone salvage robot-assisted seminal vesicle excision (RA-SVE) for the focal treatment of isolated seminal vesical (SV) recurrence after treatment for prostate cancer by low-dose-rate brachytherapy. PATIENTS AND METHODS: Patients with rising prostate-specific antigen (PSA) after low-dose-rate prostate brachytherapy (LDR-PB) underwent multi-parametric magnetic resonance imaging (mp-MRI) of the prostate and 11 C-Choline or 68 Ga-prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) scan, followed by targeted transperineal biopsy of the prostate and SVs. Isolated SV recurrence were identified in 17 (0.38%) LDR-PB patients. These 17 patients were offered RA-SVE. RESULTS: The median total operative time was 90 min and blood loss 50 mL with no postoperative transfusions required. The median hospital stay was 1 day. No intra- or postoperative complications were documented. Continence status was unaffected, no patient required urinary pads. Postoperative pathology confirmed SV invasion in all specimens. Surgical margins were positive in seven (41%) patients. All patients had at least one positive imaging study, although three (18%) mp-MRI and five (29%) PET/CT assessments were negative. One (6%) pre-SVE biopsy was also negative but with positive imaging. Salvage SVE failure, defined as three consecutive PSA rises or the need for further treatment, occurred in six patients of whom three had a positive margin. Overall failure-free survival rates were 86%, 67%, and 53% at 1, 2, and 3 years after SVE, respectively. CONCLUSIONS: Salvage RA-SVE appears to be a safe focal treatment, with very low morbidity, for patients with localised SV recurrence after LDR-PB. It permits deferral of androgen deprivation therapy in selected patients. Bilateral SVE is mandatory. This surgical option should be considered in patients with isolated prostate cancer recurrence to the SV.

Hemi-ablative low-dose-rate prostate brachytherapy for unilateral localised prostate cancer.

OBJECTIVES: To report clinical outcomes of the Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluating treatment-related toxicity and effectiveness of hemi-gland (HG) low-dose-rate (LDR) prostate brachytherapy as a focal approach to control unilateral localised prostate cancer. PATIENTS AND METHODS: Single institution phase IIS pilot study of patients treated with focal 4D Brachytherapy™ (BXTAccelyon, Burnham, Buckinghamshire, UK). The primary outcome was patient-reported toxicity 24 months after implant. The secondary outcome was assessment of disease control. Outcomes in HG patients were compared to whole-gland (WG) controls obtained from our prospective cohort registry by negative binomial and linear regression models. RESULTS: Pre-treatment demography was similar between the 30 HG patients and 362 WG controls. Post-implant dosimetry was similar for the prostate gland target volumes and significantly reduced for the urethra and bowel in HG patients relative to WG controls, but this did not translate into a difference in post-implant mean symptom scores between the two groups. Nevertheless, the change in score from baseline indicated that the impact on pre-treatment symptom status was less after HG implants. Only HG patients showed a return to baseline urinary scores as early as 12 months. Sexual potency was conserved in 73% and 67% of HG and WG patients, respectively (P = 0.84). Post-implant prostate-specific antigen (PSA) kinetics revealed that baseline PSA was reduced at 24 months by 78% and 88% in HG and WG patients, respectively (P < 0.05). Treatment relapse occurred in one (3%) HG patient 55 months after implant and in nine (3%) WG patients at 32-67 months after implant. CONCLUSION: This pilot study suggests that treatment-related toxicity and biochemical outcomes after HG implants are broadly similar to those observed with WG treatment despite the lower dose delivered by HG implants.

Net survival of men with localized prostate cancer after LDR brachytherapy.

OBJECTIVES: To compare survival of patients who received LDR prostate brachytherapy relative to that of peers in the general population of England, UK. PATIENTS AND METHODS: Net survival was estimated for 2472 cases treated between 2002 and 2016 using population-based analysis guidelines. Life tables adjusted for social deprivation in England from the Office for National Statistics were used to match patients by affluence based on their postcode. RESULTS: The median (range) age at time of brachytherapy was 66 (55-84) years, 84% resided in Southeast England, 51% under an index of deprivation quintile 5 (most affluent), 55% were clinical stage T1 and the remainder T2. Death from any cause occurred in 270 patients at a median (range) of 7 (1-17) years postimplant. Five and 10-year estimates (95% CI) of overall survival were 96% (95-97) and 90% (89-92), and net survival 103% (102-104) and 109% (107-110) respectively. The net survival remained above 100% in all age-at-treatment and clinical stage groups. CONCLUSION: Net survival above 100% indicates patients survive longer than the matched general population. The study shows for the first time the net survival of patients treated with a radical therapy for localized prostate cancer in England. The impact of treatment choice on the long-term net survival advantage requires further investigation.

Is hemi-gland focal LDR brachytherapy as effective as whole-gland treatment for unilateral prostate cancer?

PURPOSE: The Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluated hemi-gland (HG) low-dose-rate prostate brachytherapy (LDR-PB) as a focal approach to control unilateral localized prostate cancer and reduce treatment-related toxicity at 2-years postimplant. Herewith we present further outcomes with a minimum of 5 years post-implant follow-up. METHODS AND MATERIALS: Outcomes of 30 HG implants and 362 whole-gland (WG) brachytherapy controls were monitored with IPSS, urinary Quality-of-Life (QoLU), GI component of EORTC-PR25 (QoLB), and IIEF-5 instruments, and PSA values. The median (range) follow-up for HG and WG cases was 72 (60-96) months and 84 (24-144) months respectively. RESULTS: The IPSS was significantly reduced in HG relative to WG patients and trends indicating improved bowel QoL and erectile function were observed. The mean of change in PSA from baseline to last follow-up was -5.6 and -6.5 in HG and WG respectively (p = 0.1). The mean time to nadir was 4.2 and 4.8 years in HG and WG respectively (p = 0.06). Over time PSA in HG patients mirrored the sustained decline observed in WG cases but levels were higher by an average 0.5 ng/ml over WG controls (p < 0.001). Treatment failure occurred in 2 (6.7%) HG patients and in 20 (5.5%) WG cases. Five-year relapse-free survival was 97% in both groups (p = 0.7). CONCLUSIONS: At 5 years postimplant HG LDR-PB was as effective as WG treatment for control of unilateral localized prostate cancer with moderate improvement in treatment-related symptoms. Importantly, PSA is a valuable marker to assess disease control in this form of focal therapy.