EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer—2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent

COVID-19: Global Radiation Oncology’s Targeted Response for Pandemic Preparedness

Purpose During a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions. Methods and Materials Radiation oncologists from the United States and the United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage patients with prostate cancer during the COVID-19 pandemic. A RADS framework was created: remote visits, and avoidance, deferment, and shortening of radiation therapy was applied to determine appropriate approaches. Results Recommendations were provided by the National Comprehensive Cancer Network risk group regarding clinical node-positive, postprostatectomy, oligometastatic, and low-volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits of between 1 and 6 months were deemed safe based on stage of disease. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node-positive, recurrence postsurgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4 to 6 months as necessary. Ultrahypofractionation is preferred for localized, oligometastatic, and low-volume M1, and moderate hypofractionation is preferred for postprostatectomy and clinical node positive disease. Salvage is preferred to adjuvant radiation. Conclusions Resources can be reduced for all identified stages of prostate cancer. The RADS (remote visits, and avoidance, deferment, and shortening of radiation therapy) framework can be applied to other disease sites to help with decision making in a global pandemic.

Prostate Cancer Radiation Therapy Recommendations in Response to COVID-19

Unity Elekta is a unique magnetic resonance (MR)-linac that conjugates a 1.5 Tesla MR unit with a 7 MV flattening filter free accelerator.A prospective observational study for the clinical use of Elekta Unity is currently ongoing in our department. Herein, we present our preliminary report on the feasibility, quality of life, and patient-reported outcomes measures (PROMs) for localized prostate cancer (PC) treated with stereotactic body radiotherapy (SBRT). The SBRT protocol consisted of a 35 Gy schedule delivered in 5 fractions within 2 weeks. Toxicity and quality of life (QoL) were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v5.0, International Prostatic Symptoms Score (IPSS), ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires. Between October 2019 and January 2020, 25 patients with localized PC were recruited. The median age was 68 years (range, 54–82); 4 were low risk, 11 favorable intermediate risk (IR) and 10 unfavorable IR. Median iPSA was 6.8 ng/ml (range, 1–19), and 9 of these patients (36%) received concurrent androgen deprivation therapy. Median prostate volume was 36 cc (range, 20–61); median baseline IPSS was 5 (range, 0–10). Median time for fraction was 53 min (range, 34–86); adaptive strategy with daily critical structure and target re-contouring and daily replanning (adapt to shape) was performed in all cases. No grade ≥ 3 adverse event was observed, three patients (12%) reported grade 2 acute genitourinary toxicity (urinary frequency, urinary tract pain and urinary retention), while only one patient reported mild rectal pain. No relevant deteriorations were reported in PROMs. To the best of our knowledge, this is the first experience reporting feasibility, clinician-reported outcome measurements, and PROMs for 1.5 T MR-guided adaptive SBRT for localized prostate cancer. The preliminary data collected here report optimal safety and excellent tolerability, as also confirmed by PROMs questionnaires. Moreover, the data on technical feasibility and timing of online daily adapted planning and delivery are promising. More mature data are warranted. Date of approval April 2019 and numbered MRI/LINAC n°23,748.

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1.5 T MR-guided and daily adapted SBRT for prostate cancer: feasibility, preliminary clinical tolerability, quality of life and patient-reported outcomes during treatment

Primary endpoint analysis of the multicentre phase II hypo-FLAME trial for intermediate and high risk prostate cancer.

Summary Background Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer. Methods PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0–2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1–2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov , NCT01584258 . PACE-B recruitment is complete and follow-up is ongoing. Findings Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference −1·9 percentage points, 95% CI −6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference −4·2 percentage points, 95% CI −10·0 to 1·7; p=0·16). No treatment-related deaths occurred. Interpretation Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity. Funding Accuray and National Institute of Health Research.

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Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial.

Cancer that has invaded the detrusor muscle can be associated with a high degree of morbidity and mortality. Radical treatments are required, including cystectomy, radiotherapy and chemotherapy. These treatments can cause short-term and long-term consequences for patients. In this article the authors describe the current treatment approaches to muscle-invasive bladder cancer.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/tre.489

Hans van der Voet

Papers

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial.

Management of muscle-invasive bladder cancer