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.

Folliculitis-perifolliculitis related to erlotinib therapy spares previously irradiated skin.

Erlotinib, a specific epidermal growth factor receptor tyrosine kinase inhibitor, is used to treat various metastatic cancers. It is known to cause an acneiform rash. Herein, we report a case where the rash spared the previous radiotherapy field. A limitation of this study is that it is an anecdotal case report. Further research into the pathologic process of the rash is warranted to understand the reason for its absence in the irradiated skin.

Impact of selection of post-implant technique on dosimetry parameters for permanent prostate implants.

PURPOSE: To investigate the variability of prostate implant quality indices between three different methods of calculating the post-implant dose distribution. METHODS AND MATERIALS: In a study of 9 permanent prostate implant patients, post-implant dosimetry was carried out using three methods of identifying seed positions within the prostate volume: (1) prostate volumes defined by transrectal ultrasound (TRUS) immediately following implant were registered with shift-film defined seed positions, (2) seeds were identified directly from the post-implant TRUS images, and (3) CT was used to define seed positions and prostate volumes from images acquired at 41-65 days post-implant. For each method, the volume of prostate receiving 90%, 100%, and 150% of the prescribed dose (V90, V100, V150) and the dose delivered to 90% of the prostate volume (D90) were calculated. RESULTS: Post-implant TRUS volumes were within 15% of the preimplant TRUS volumes in 8 of the 9 patients investigated. The post-implant CT volume was within 15% of the preimplant (TRUS) volume in only 3 of the 9 cases. The value of the dosimetry parameters was dependent on the method used and varied by 5-25% for V90, 5-30% for V100, 42-134% for V150, and 9-60% for D90. No simple relationship was found between change in volume and the resultant change in dosimetry parameter. Differences in dosimetry parameters due to source localization uncertainties was found to be small (< or = 10% for V100) when comparing methods (1) and (2). CONCLUSIONS: There are many uncertainties in the calculation of parameters that are commonly used to describe the quality of a permanent prostate implant. Differences in the parameters calculated were most likely a result of a combination of factors including uncertainties in delineating the prostate with different imaging modalities, differences in source identification techniques, and intraobserver variability.

Prostatic adenocarcinoma masquerading as lymphoma and presentation with axillary-subclavian vein thrombosis.

Axillary and/or subclavian vein thrombosis is a relatively rare disease, constituting about 2% of all cases of deep venous thrombosis (DVT). We report on a patient who presented with axillary-subclavian vein thrombosis and had metastatic prostatic adenocarcinoma.

Impact of prostate volume evaluation by different observers on CT-based post-implant dosimetry.

PURPOSE: An analysis of computed tomography (CT)-based dosimetry was performed to evaluate the variability of different observers' judgements in marking the prostate gland on CT films, and its effect on the parameters that characterise the prostate implantation quality. Accuracy of data entry by the first author in the process of dosimetry procedure has also been evaluated. MATERIALS AND METHODS: Four observers were asked to evaluate the prostate volume on CT films for six different patients. Each observer repeated the evaluation six times. The sample of patients has a prostate volume in the range of 21.4-42.0 cc derived from transrectal ultrasound volume study. After an average period of 6 weeks of the I-125 implantation, all patients had CT scans. CT-based post-implant dosimetry was performed and the dose volume histograms DVHs were calculated to report the re-constructed prostate volume, Vp100, Vp150, Vp90 and D90. Comparison between the four observers' output was performed. RESULTS: Comparison between the four observers shows that each observer has a different way of estimating the prostate on CT films. Observers' precision also varies according to the prostate volume and the image quality. This can cause a variation in the resulting D90 value by up to 50%. Analysis of data entry shows a high degree of accuracy. The error of digitizing the prostate is +/-0.19 cc. This is correlated to an error of +/-0.78 Gy of the D90. CONCLUSION: The evaluation of prostate gland volume on CT films varies between different observers. This has an effect on the dosimetric indices that characterise the implant quality in particular the D90.