Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial.

BACKGROUND: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. INTERPRETATION: Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial.

BACKGROUND: Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. METHODS: RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. INTERPRETATION: Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.

Effects of bariatric surgery on urinary and sexual function.

OBJECTIVE: To investigate the effects of weight loss and time post laparoscopic gastric banding surgery (LGB) on urinary and sexual function. MATERIALS AND METHODS: 653 females and 145 males who underwent LGB over the last 10 years at a single centre in Australia were contacted by post and asked to complete validated questionnaires. RESULTS: The pre-surgery body-mass index (BMI) was higher in males than females (47.3 vs 43.5); 65% of the females and 24% of males previously had some degree of urinary incontinence (UI). There were significant weight and BMI losses in males and females (23.2 kg and 7.51 vs 22.7 kg and 8.28; P < 0.0001). In females there were significant improvements in the ICIQ-SF (P= 0.0008) and Quality of Life (P < 0.0001) scores. For each kilogram lost there was a 0.05 improvement in the ICIQ score (P= 0.03) in females. There were also postoperative improvements in all symptoms of UI and stress incontinence in females but urge incontinence worsened, when adjusted for weight loss. In males there was no improvement in UI with weight loss after LGB. There was no relationship with time and UI in either gender; 83.3% of males reported a degree of ED before LGB. There was improvement in the IIEF score in males post LGB but there was worsening of erectile index (P= 0.005) and orgasmic function (P= 0.002) when adjusted for time. More males had started using phosphodiesterase type 5 inhibitors, post-LGB. CONCLUSIONS: Surgically induced weight loss by LGB improved overall UI, quality of life and stress incontinence in females but urge incontinence worsened. There was no improvement in UI with weight-loss or overall sexual function after LGB in males. However, erectile index and orgasmic function worsened when adjusted for time. Further evaluation is required by means of larger prospective studies involving urodynamic testing.

Initial treatment costs of organ-confined prostate cancer: a general perspective.

With the increasing prevalence of prostate cancer and evolving methods for the definitive treatment of OCPCa, health economic analyses will be critically important, albeit difficult to carry out. Preliminary studies point to RPP as the most cost-effective treatment for OCPCa. The quickest postoperative recovery, in experienced hands, occurs in RARP and RPP, with ORPP having a slightly, but statistically in significant, shorter hospital stay. It should be stressed that initial treatment costs are not the only important factor in healthcare costs. Readmission for early and late complications and the loss of productivity resulting from variation in time to return to work, need also to be considered. Loss of productivity may also vary in cost between different institutions and countries depending upon the proportion of patients employed. Further large-scale multicentre studies are necessary to assess this.

What is the significance of pT0 at cystectomy?

The current treatment for muscle invasive bladder cancer is radical cystectomy. However, this approach leads to significant changes in the patient's quality of life, as well as potential treatment failure. And so, with the introduction of alternative and neoadjuvant therapies available, the presence of pT0 tumour at cystectomy confers a number of issues. The variability in numbers of pT0 tumours at cystectomy highlights the importance of adequate clinical staging, as well as the increasing successful use of neoadjuvant chemotherapy. Although current literature is limited, patients with prior clinical stage of muscle-invasive but node-negative disease are likely to demonstrate the most improvement in survivability if they subsequently develop pT0 at cystectomy. This review also highlights the importance of response to chemotherapy as an indicator of subsequent prognosis. With increasing numbers of pT0 tumours seen at radical cystectomy, it is suggested that more conservative measures, such as re-staging following neoadjuvant chemotherapy and even 'selective bladder preservation' treatment, may be the future for the management of muscle invasive bladder cancer.