Sara J. Khaksar

Biochemical (prostate-specific antigen) relapse-free survival and toxicity after 125I low-dose-rate prostate brachytherapy

To report our clinical experience and 5‐year prostate‐specific antigen (PSA) relapse‐free survival rate for early‐stage prostate cancer after 125I low‐dose‐rate prostate brachytherapy.

Novel prostate brachytherapy technique: Improved dosimetric and clinical outcome

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 (D(25) as %mPD - Group 1: 61.2+/-35.7, Group 2: 29.7+/-16.0, p<0.0001; D(50) as %mPD - Group 1: 45.8+/-26.9, Group 2: 21.4+/-11.7, p<0.0001) whilst improving prostate dosimetry (D(90) - 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.

Management of prostate cancer. Part 2: localized and locally advanced disease

Prostate cancer is the most prevalent nondermatological malignancy affecting men in the Western world. An increase in public awareness has led to earlier detection. Accepted treatments for localized prostate cancer include active surveillance, radical prostatectomy, interstitial brachytherapy, external beam radiotherapy and watchful waiting. The authors discuss the rationale for the different approaches together with outcomes including toxicity. Novel approaches are also explored. The management of locally advanced disease has long been a challenge and the evolving evidence is reviewed.

Management of prostate cancer. Part 3: metastatic disease

Despite the increased detection of prostate cancer at an early stage, men are still dying of this disease. Management of advanced disease focuses on controlling the disease process, palliation of symptoms and improving quality of life. In this review, the basis for androgen deprivation in hormone-dependent disease is discussed and the role of maximum and intermittent androgen deprivation, as well as management options for hormone-refractory disease is addressed. Local radiotherapy continues to be of importance in pain control and the maintenance of quality of life. Radiopharmaceuticals and bisphosphonates also have a role to play, the latter particularly in the reduction of skeletal-related events. Chemotherapy in hormone-refractory disease is now well established following pivotal trials demonstrating a survival benefit with docetaxel. The emergence of novel agents targeting growth factors, angiogenesis and immunotherapy present exciting possibilities for future treatment.

Long-term oncological outcomes and toxicity in 597 men aged ≤60 years at time of low-dose-rate brachytherapy for localised prostate cancer

To report oncological and functional outcomes of men treated with low‐dose‐rate (LDR) prostate brachytherapy aged ≤60 years at time of treatment.

Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial

Summary Background 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. Methods 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. Findings 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). Interpretation Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer. Funding Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.

Low-dose-rate brachytherapy for the treatment of localised prostate cancer in men with a high risk of disease relapse

To report clinical outcomes of 125I low‐dose‐rate prostate brachytherapy (LDR‐PB) as monotherapy or combined with androgen‐deprivation therapy (ADT) and/or external beam radiotherapy (EBRT) in high‐risk localised prostate cancer.