With the recent introduction of novel treatment options, real-world data from patients with metastatic castration-resistant prostate cancer (mCRPC) are required to better understand the impact on ...routine clinical practice. This study primarily aimed to describe the time to treatment failure (TTF) of mCRPC patients treated with abiraterone acetate plus prednisone or the corticosteroid of choice (AAP) in the pre-chemotherapy setting. Other relevant outcomes, clinical and treatment characteristics of these patients were also evaluated.
This retrospective, observational study collected data from chemotherapy-naïve mCRPC patients treated with AAP from four European countries. Kaplan-Meier curves were used to estimate TTF, progression-free survival (PFS), and time to first skeletal-related event. The impact of baseline characteristics on TTF and PFS was explored using univariate and multivariate Cox proportional hazard models. Log-rank test was used to assess the potential role of duration of response to ADT in predicting response to AAP treatment.
Data from 481 eligible patients (Belgium: 68; France: 61; Germany: 150; UK: 202) were analysed. At AAP initiation, the median age of patients was 75.0 years (interquartile range IQR: 69.0-81.0), and the median PSA was 56.2 ng/mL (IQR: 22.2-133.1), with over 50% of patients presenting an ECOG score of 0 or 1. Visceral metastases were present in 7.5% of patients; an exclusion criterion in the COU-AA-302 clinical trial. The median TTF with AAP was 10.0 months (95%CI: 9.2-11.1) and the median PFS was 10.8 months (95%CI: 9.6-11.8). Shorter TTF was significantly associated with higher ALP (> 119 units/L), higher PSA (> 56.2 ng/mL), or poorer ECOG PS scores at AAP initiation (p < 0.05). Patients with longer duration of response to ADT (≥12 months) presented longer TTF and longer time to progression (p < 0.0001).
This European real-world study provides valuable insights into the characteristics, treatment, and outcomes of chemotherapy-naïve patients with mCRPC who received AAP in routine clinical practice. Treatment effectiveness of AAP in the real-world is maintained despite patients having poorer clinical features at initiation than those observed in the COU-AA-302 trial population.
Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients ...with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.
We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule. This trial is registered with ClinicalTrials.gov, number NCT00268476.
Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63–73) and median amount of prostate-specific antigen of 97 ng/mL (33–315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival (HR 0·76, 95% CI 0·68–0·84; p<0·0001) but not overall survival (0·92, 0·80–1·06; p=0·266). Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3–4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 38% with control and 380 39% with radiotherapy).
Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer.
Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.
Abstract Purpose Erectile dysfunction following prostate brachytherapy is reported to be related to dose received by the penile bulb. To minimise this, whilst preserving prostate dosimetry, we have ...developed a technique for I-125 seed brachytherapy using both stranded seeds and loose seeds delivered with a Mick applicator, and implanted via the sagittal plane on trans-rectal ultrasound. Materials and methods Post-implant dosimetry and potency rates were compared in 120 potent patients. In Group 1, 60 patients were treated using a conventional technique of seeds implanted in a modified-uniform distribution. From January 2005, a novel technique was developed using stranded seeds peripherally and centrally distributed loose seeds implanted via a Mick applicator (Group 2). The latter technique allows greater flexibility when implanting the seeds at the apex. Each patient was prescribed a minimum peripheral dose of 145 Gy. No patients received external beam radiotherapy or hormone treatment. There was no significant difference in age or pre-implant potency score (mean IIEF-5 score 22.4 vs. 22.6, p = 0.074) between the two groups. Results The new technique delivers lower penile bulb doses ( D25 as %mPD – Group 1: 61.2 ± 35.7, Group 2: 29.7 ± 16.0, p < 0.0001; D50 as %mPD – Group 1: 45.8 ± 26.9, Group 2: 21.4 ± 11.7, p < 0.0001) whilst improving prostate dosimetry ( D90 – Group 1: 147 Gy ± 21.1, Group 2: 155 Gy ± 16.7, p = 0.03). At 2 years, the potency rate was also improved: Group 1: 61.7%; Group 2: 83.3% ( p = 0.008). Conclusions In this study, the novel brachytherapy technique using both peripheral stranded seeds and central loose seeds delivered via a Mick applicator results in a lower penile bulb dose whilst improving prostate dosimetry, and may achieve higher potency rates.
To compare survival of patients who received LDR prostate brachytherapy relative to that of peers in the general population of England, UK.
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.
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.
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.
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 11C‐Choline or 68Ga‐prostate‐specific membrane antigen (68Ga‐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.
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.
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.
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.
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.
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).
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.
Objectives
To report oncological and functional outcomes of men treated with low‐dose‐rate (LDR) prostate brachytherapy aged ≤60 years at time of treatment.
Patients and Methods
Of 3262 patients ...treated with LDR brachytherapy at our centre up to June 2016, we retrospectively identified 597 patients aged ≤60 years at treatment with ≥3‐years post‐implantation follow‐up and four prostate‐specific antigen (PSA) measurements, of which one was at baseline. Overall survival (OS), prostate cancer‐specific survival (PCSS) and relapse free survival (RFS) were analysed together with prospectively collected physician‐reported adverse events and patient‐reported symptom scores.
Results
The median (range) age was 57 (44‐60) years, follow‐up was 8.9 (1.5‐17.2) years, and PSA follow‐up 5.9 (0.8‐15) years. Low‐, intermediate‐ and high‐risk disease represented 53%, 37% and 10% of the patients, respectively. At 10 years after implantation OS and PCSS were 98% and 99% for low‐risk, 99% and 100% for intermediate‐risk, and 93% and 95% for high‐risk disease, respectively. At 10 years after implantation RFS, using the PSA level nadir plus 2 ng/mL definition, was 95%, 90% and 87% for low‐, intermediate‐, and high‐risk disease, respectively. Urinary stricture was the most common genitourinary adverse event occurring in 19 patients (3.2%). At 5 years after implantation erectile function was preserved in 75% of the patients who were potent before treatment.
Conclusion
LDR brachytherapy is an effective treatment with long‐term control of prostate cancer in men aged ≤60 years at time of treatment. It was associated with low rates of treatment‐related toxicity and can be considered a first‐line treatment for prostate cancer in this patient group.
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