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CHHiP is a randomized trial evaluating moderately hypofractionated radiation therapy for treatment of localized prostate cancer. Of all participants, 97% of them had concurrent short-course hormone therapy (HT), either luteinizing hormone-releasing hormone analog (LHRHa) or 150 mg of bicalutamide daily. This exploratory analysis compares efficacy and side effects in a nonrandomized comparison.In our study, 2700 patients received LHRHa and 403 received bicalutamide. The primary endpoint was biochemical/clinical failure. Groups were compared with Cox regression adjusted for various prognostic factors and stratified by radiation therapy dose. A key secondary endpoint was erectile dysfunction (ED) assessed by clinicians (using scores from Late Effects on Normal Tissues: Subjective/Objective/Management [LENT-SOM] subjective erectile function for vaginal penetration) and patients (single items within the University of California-Los Angeles Prostate Cancer Index [UCLA PCI] and Expanded Prostate Cancer Index Composite [EPIC]-50 questionnaires) at 2 years and compared between HT regimens by χBicalutamide patients were significantly younger (median 67 vs 69 years LHRHa). Median follow-up was 9.3 years. There was no difference in biochemical or clinical failure with an adjusted hazard ratio or 0.97 (95% confidence interval, 0.77-1.23; P = .8). At 2 years, grade ≥2 LENT-SOM ED was reported in significantly more LHRHa patients (313 out of 590; 53%) versus bicalutamide (17 out of 68; 25%) (P.0001). There were no differences in ED seen with UCLA-PCI and EPIC-50 questionnaires.In this nonrandomized comparison, there was no evidence of a difference in efficacy according to type of HT received. Bicalutamide preserved clinician assessed (LENT-SOM) erectile function at 2 years but patient-reported outcomes were similar between groups.

Purpose: High-field magnetic resonance-linear accelerators (MR-Linacs), linear accelerators combined with a diagnostic magnetic resonance imaging (MRI) scanner and online adaptive workflow, potentially give rise to novel online anatomic and response adaptive radiation therapy paradigms. The first high-field (1.5T) MR-Linac received regulatory approval in late 2018, and little is known about clinical use, patient tolerability of daily high-field MRI, and toxicity of treatments. Herein we report the initial experience within the MOMENTUM Study (NCT04075305), a prospective international registry of the MRLinac Consortium. Methods and Materials: Patients were included between February 2019 and October 2020 at 7 institutions in 4 countries. We used descriptive statistics to describe the patterns of care, tolerability (the percentage of patients discontinuing their course early), and safety (grade 3-5 Common Terminology Criteria for Adverse Events v.5 acute toxicity within 3 months after the end of treatment). Results: A total 943 patients participated in the MOMENTUM Study, 702 of whom had complete baseline data at the time of this analysis. Patients were primarily male (79%) with a median age of 68 years (range, 22-93) and were treated for 39 different indications. The most frequent indications were prostate (40%), oligometastatic lymph node (17%), brain (12%), and rectal (10%) cancers. The median number of fractions was 5 (range, 1-35). Six patients discontinued MR-Linac treatments, but none due to an inability to tolerate repeated high-field MRI. Of the 415 patients with complete data on acute toxicity at 3 month follow-up, 18 (4%) patients experienced grade 3 acute toxicity related to radiation. No grade 4 or 5 acute toxicity related to radiation was observed. Conclusions: In the first 21 months of our study, patterns of care were diverse with respect to clinical utilization, body sites, and radiation prescriptions. No patient discontinued treatment due to inability to tolerate daily high-field MRI scans, and the acute radiation toxicity experience was encouraging. (c) 2021 Published by Elsevier Inc.

Background Radium-223 is a bone-seeking, alpha-emitting radionuclide used in metastatic castration-resistant prostate cancer (mCRPC). Radium-223 increases the risk of fracture when used in combination with abiraterone and prednisolone. The risk of fracture in men receiving radium-223 monotherapy is unclear. Patients and Methods This was a prospective, multicenter phase II study of radium-223 in 36 men with mCRPC and a reference cohort (n = 36) matched for fracture risk and not treated with radium-223. Bone fractures were assessed using whole-body magnetic resonance imaging. The primary outcome was risk of new fractures. Results Thirty-six patients were treated with up to six 4-week cycles of radium-223. With a median follow-up of 16.3 months, 74 new fractures were identified in 20 patients. Freedom from fracture was 56% (95% confidence interval, 35.3-71.6) at 12 months. On multivariate analysis, prior corticosteroid use was associated with risk of fracture. In the reference cohort (n = 36), 16 new fractures were identified in 12 patients over a median follow-up of 24 months. Across both cohorts, 67% of all fractures occurred at uninvolved bone. Conclusions Men with mCRPC, and particularly those treated with radium-223, are at risk of fracture. They should receive a bone health agent to reduce the risk of fragility fractures., Micro-Abstract Radium-223 increases the risk of fracture in combination with abiraterone and prednisolone. The fracture risk of radium-223 monotherapy is unclear. This prospective study assessed fracture incidence in men treated with radium-223 matched with a cohort that did not have radium-223. We identified 74 new fractures in 20 patients receiving radium-223. Most fractures occurred in bones without apparent metastases. Bone health agents should be mandatory before starting radium-223.

OBJECTIVE: To assess the impact of centralization of prostate cancer surgery and radiotherapy services on the choice of prostate cancer treatment. PATIENTS AND METHODS: This national population-based study used linked cancer registry data and administrative hospital-level data for all 16 621 patients who were diagnosed between 1 January 2017 and 31 December 2018 with intermediate-risk prostate cancer and who underwent radical prostatectomy (RP) or radical radiation therapy (RT) in the English National Health Service (NHS). Travel times by car to treating centres were estimated using a geographic information system. We used logistic regression to assess the impact of the relative proximity of alternative treatment options on the type of treatment received, with adjustment for patient characteristics. RESULTS: Of the 78 NHS hospitals that provide RT or RP for prostate cancer, 41% provide both, 36% provide RT and 23% provide RP. Compared to patients who had both treatment options available at their nearest centre where overall 57% of patients received RT and 43% RP, patients were less likely to receive RT if their nearest centre offered RP only and the extra travel time to a hospital providing RT was >15 min (52% of patients received RT and 48% RP%, odds ratio [OR] 0.70 (0.58-0.85); P 15 min (63% of patients received RT and 37% RP, OR 1.23 (1.08-1.40); P

Background and purpose Transperineal ultrasound (TPUS) is used clinically for directly assessing prostate motion. Factors affecting accuracy and precision in TPUS motion estimation must be assessed to realise its full potential. Methods and materials Patients were imaged using volumetric TPUS during the Clarity-Pro trial (NCT02388308). Prostate motion was measured online at patient set-up and offline by experienced observers. Cone beam CT with markers was used as a comparator and observer performance was also quantified. The influence of different clinical factors was examined to establish specific recommendations towards efficacious ultrasound guided radiotherapy. Results From 330 fractions in 22 patients, offline observer random errors were 1.5 mm, 1.3 mm, 1.9 mm (left–right, superior-inferior, anteroposterior respectively). Errors increased in fractions exhibiting poor image quality to 3.3 mm, 3.3 mm and 6.8 mm. Poor image quality was associated with inconsistent probe placement, large anatomical changes and unfavourable imaging conditions within the patient. Online matching exhibited increased observer errors of: 3.2 mm, 2.9 mm and 4.7 mm. Four patients exhibited large systematic residual errors, of which three had poor quality images. Patient habitus showed no correlation with observer error, residual error, or image quality. Conclusions TPUS offers the unique potential to directly assess inter- and intra-fraction motion on conventional linacs. Inconsistent image quality, inexperienced operators and the pressures of the clinical environment may degrade precision and accuracy. Experienced operators are essential and cross-centre standards for training and QA should be established that build upon current guidance. Greater use of automation technologies may further minimise uncertainties.

Highlights • Deliverable plans for 1 and 2 fraction SBRT can be created for the Unity MR-Linac. • Dose constraints and objectives from HDR and SBRT clinical studies were applied. • In 40% of 1 and 2 fraction plans target doses were compromised to meet OAR goals., The drive towards hypofractionated prostate radiotherapy is motivated by a low alpha/beta ratio for prostate cancer (1 to 3 Gy) compared to surrounding organs at risk, implying an improved therapeutic ratio with increasing dose per fraction. Early evidence from studies of ultrahypofractionated (UHF) prostate HDR brachytherapy has shown good tolerability in terms of normal tissue toxicities and clinical outcomes similar to conventional fractionation schedules. MR-guided stereotactic body radiotherapy (SBRT) with online plan adaptation and real-time tumour imaging may enable UHF doses to be delivered to the prostate safely, without the invasiveness of brachytherapy. The feasibility of UHF prostate treatment planning for the Unity MR-Linac (MRL, Elekta AB, Stockholm) was investigated for target prescriptions and planning constraints derived from the HDR brachytherapy and SBRT literature. Monaco 5.40 (Elekta) was used to generate MRL step-and-shoot IMRT plans for three dose fractionation protocols (5, 2 and 1 fractions), for ten randomly selected previously treated prostate cancer patients. Of the ten plans per UHF scheme, all clinical goals were met in all cases for 5 fractions, and in six cases for both 2 and 1 fraction schemes. PTV D95% was compromised by up to 6.4% and 3.9% of the associated target dose for 2 and 1 fraction plans respectively. There were two cases of PTV D95% compromise greater than a 5% dose decrease for the 2 fraction plans. The study suggests feasibility of the UHF treatment planning approaches if combined with real-time motion mitigation strategies.

Objective To present the long‐term adjuvant radiotherapy outcomes of patients with pN3 squamous cell carcinoma of the penis (SCCp) treated at two UK centres. Patients and Methods We conducted a retrospective audit of all pN3 SCCp patients, deemed suitable for adjuvant therapy by a specialist multidisciplinary team at St George’s and Leeds Hospitals, who received adjuvant radiotherapy. Primary outcomes were recurrence‐free survival (RFS), cancer‐specific survival (CSS) and overall survival (OS). Secondary outcomes were time to adjuvant treatment, frequency of in‐field recurrence, site and side of recurrence, and dose and schedule of radiotherapy. Results A total of 146 patients were included: 121 completed radiotherapy, four did not complete radiotherapy and 21 did not start it. The median (interquartile range [IQR]) age was 59 (54–70)years. The 5‐year RFS was 51%, CSS was 51% and OS was 44%. Adjuvant radiotherapy was started at a median (IQR) of 75 (48–106) days. A dose of 45 Gy in 20 fractions was most commonly used. Of the 125 patients who started adjuvant treatment, 55 relapsed. Of these relapses, 30 occurred in an inguinal or pelvic nodal station and 26 of the 30 were in a radiation field. Relapses in 18 of the 55 cases were in visceral sites only and seven were in both nodal (non‐irradiated sites) and visceral sites. Doses of 50 Gy) were more commonly used after 2013. Conclusions Application of a standard radiotherapy protocol within a centralized supra‐network setting has achieved survival outcomes that would appear better than those previously documented for either radiotherapy or chemotherapy in a cohort with solely pN3 disease. The addition of adjuvant chemotherapy may improve these outcomes further. These data suggest that adjuvant radiotherapy has a role to play in the management of men with pN3 SCCp.

Highlights • PIVOTALboost evaluates benefits/toxicity of pelvic node RT and focal boost dose escalation. • Unfavourable intermediate/high risk and bulky local disease are most likely to benefit. • Functional MRI imaging is used to select patients for different types of dose escalation. • HDR brachytherapy or focal dose escalation with IMRT are used as options. • Training and support is provided to reduce variations of contouring and radiotherapy planning. • The trial is recruiting patients in 38 radiotherapy centres through the UK.

Highlights • Dose escalation to MRI-defined prostate lesions using SABR is feasible and safe. • After an extended follow up, rates of Grade 2 + GU and GI toxicities were low. • No biochemical relapse was observed. • 10 minor dose variations were reported out of 80 ideal dose constraints., Introduction Dose escalation to dominant intraprostatic lesions (DILs) is a novel method to increase the therapeutic ratio in localised prostate cancer. The Stereotactic Prostate Augmented Radiotherapy with Cyberknife (SPARC) trial was designed to determine the feasibility of a focal boost defined with multiparametric magnetic resonance imaging (mpMRI) using stereotactic ablative body radiotherapy (SABR). Materials and methods Patients were included with newly diagnosed intermediate to high risk prostate cancer with at least one of: Gleason score 4 + 3, stage T3a, or PSA > 20 ng/ml. Visible disease on mpMRI was mandatory and up to 2 separate nodules were allowed. All patients received androgen deprivation. Patients received 36.25 Gy in 5 fractions using CyberKnife® and the DIL received a simultaneous boost to a maximum of 47.5 Gy, as allowed by OAR constraints. Genitourinary (GU) and gastrointestinal (GI) toxicity was reported using the RTOG scoring criteria. International Index of Erectile Function (IIEF) and EQ-5D global health scores were regularly captured. Results An interim safety analysis was performed on the first 8 patients, recruited between July 2013 and December 2015. Median follow up was 56 months (range 50–74). Median D95 values for the prostate PTV and boost volume were 36.55 Gy (range 35.87–36.99) and 46.62 Gy (range 44.85–48.25) respectively. Of the dose constraints, 10/80 were not achieved but all were minor dose variations. Grade 2+ acute GU and GI toxicities were 37.5% respectively while grade 2+ late GU and GI toxicities were 12.5% and 0% respectively. IIEF and quality of life scores recovered over time and all patients remain in biochemical remission. Conclusion The first patients have been successfully treated with prostate SABR and focal boost on the SPARC trial, with excellent adherence to the planning protocol. Toxicity and efficacy results are promising and further recruitment is underway.

Purpose Red cell distribution width (RDW) measures red cells’ size variability. Metastatic penile cancer displays poor chemotherapy response. As no validated prognostic predictor exists, we investigated whether RDW correlates independently with survival outcomes in metastatic penile cancer treated by chemotherapy. Methods Electronic chemotherapy files of patients with metastatic penile cancer (M1 or N3) from a large academic supra-regional centre were retrospectively analysed between 2005 and 2018. Patients were stratified into RDW > 13.9% and Results 58 patients were analysed. The RDW-high group (n = 31) had a poorer survival than the RDW-low group (n = 27). Median overall survival (mOS) in all patients was 19.0 months (95% CI 13.1–24.9). mOS for RDW-high was 15.0 months (95% CI 10.1–19.9) and 37.0 months (95% CI 32.3–43.1) for RDW-low. Kaplan–Meier curves showed a clear disparity in survival (log rank p = 0.025). Cox proportional hazard ratio for death, corrected for T-stage, grade, age and deprivation score was 0.43 (p = 0.04). Sub-analysis of the M1 patients showed mOS in RDW-high of 17 m (95% CI 11.6–22.4) vs. NR; HR for death of 0.42. N3 patients’ mOS in RDW-high cohort was 30 months (95% CI 4.5–55.9) vs. 13 months (95% CI 1.8–24.2) in RDW-low; HR for death was 0.30. Conclusion RDW correlates independently with survival outcomes in metastatic penile cancer and may act as a potential predictor of survival outcomes for patients with metastatic penile cancer receiving chemotherapy.

Highlights • Automated matching improves accuracy and precision of ultrasound guided radiotherapy. • Image registration software lowers setup errors and sonography training requirements. • Spatial regularisation improves registration algorithm performance., Background and purpose Daily image guidance is standard care for prostate radiotherapy. Innovations which improve the accuracy and efficiency of ultrasound guidance are needed, particularly with respect to reducing interobserver variation. This study explores automation tools for this purpose, demonstrated on the Elekta Clarity Autoscan®. The study was conducted as part of the Clarity-Pro trial (NCT02388308). Materials and methods Ultrasound scan volumes were collected from 32 patients. Prostate matches were performed using two proposed workflows and the results compared with Clarity’s proprietary software. Gold standard matches derived from manually localised landmarks provided a reference. The two workflows incorporated a custom 3D image registration algorithm, which was benchmarked against a third-party application (Elastix). Results Significant reductions in match errors were reported from both workflows compared to standard protocol. Median (IQR) absolute errors in the left–right, anteroposterior and craniocaudal axes were lowest for the Manually Initiated workflow: 0.7(1.0) mm, 0.7(0.9) mm, 0.6(0.9) mm compared to 1.0(1.7) mm, 0.9(1.4) mm, 0.9(1.2) mm for Clarity. Median interobserver variation was ≪0.01 mm in all axes for both workflows compared to 2.2 mm, 1.7 mm, 1.5 mm for Clarity in left–right, anteroposterior and craniocaudal axes. Mean matching times was also reduced to 43 s from 152 s for Clarity. Inexperienced users of the proposed workflows attained better match precision than experienced users on Clarity. Conclusion Automated image registration with effective input and verification steps should increase the efficacy of interfraction ultrasound guidance compared to the current commercially available tools.

Advances in radiotherapy technology have increased precision of treatment delivery and in some tumour types, improved cure rates and decreased side effects. A new generation of radiotherapy machines, hybrids of an MRI scanner and a linear accelerator, has the potential to further transform the practice of radiation therapy in some cancers. Facilitating superior image quality and the ability to change the dose distribution online on a daily basis (termed “daily adaptive replanning”), MRI-guided radiotherapy machines allow for new possibilities including increasing dose, for hard to treat cancers, and more selective sparing of healthy tissues, where toxicity reduction is the key priority. These machines have already been used to treat most types of cancer, although experience is still in its infancy. This review summarises the potential and current evidence for MRI-guided radiotherapy, with a predominant focus on prostate cancer. Current advantages and disadvantages are discussed including a realistic appraisal of the likely potential to improve patient outcomes. In addition, horizon scanning for near-term possibilities for research and development will hopefully delineate the potential role for this technology over the next decade.

304 Background: Five-year results from the CHHiP trial indicated that moderate hypofractionation of 60 Gray (Gy)/20 fractions (f) was non-inferior to 74Gy/37f (Lancet Oncology, 2016). Reporting of long-term efficacy and side effects is essential in a patient population that remain at risk of recurrence years after treatment. Here we report specific co-morbidity data collected at 10 years and an update of efficacy. Methods: Between October 2002 and June 2011, 3216 men with node negative T1b-T3a localised prostate cancer with risk of seminal vesical involvement ≤30% were randomised (1:1:1 ratio) to 74Gy/37f (control), 60Gy/20f or 57Gy/19f. Patients received 3-6 months of androgen deprivation prior to radiotherapy. The primary endpoint was time to biochemical failure (Phoenix consensus guidelines) or clinical failure (BCF). The non-inferiority design specified a critical hazard ratio (HR) of 1.208 for each hypofractionated schedule compared to control. Data on specific radiotherapy related co-morbidities were collected at 10-year follow-up and are presented as frequency and percentages. Analysis was by intention-to-treat; HRs quoted are unadjusted. Results: With a median follow up of 12.1 years, 10-year BCF-free rates (95% CI) were 74Gy: 76.0% (73.1%, 78.6%); 60Gy: 79.8% (77.1%, 82.3%) and 57Gy: 73.4% (70.5%, 76.1%). For 60Gy/20f, non-inferiority was confirmed: HR60=0.84 (90% CI 0.72, 0.97) with borderline significance for superiority (HR=0.84 (95% CI 0.70, 1.00). As in the primary analysis, for 57Gy/19f, non-inferiority could not be declared: HR57=1.13 (90% CI 0.98, 1.30). 10-year overall survival (95% CI) was 78.5% (75.9%, 81.0%), 82.9% (80.4%, 85.0%) and 79.9% (77.3%, 82.2%) in the 74Gy, 60Gy and 57Gy groups. Bone fractures were reported in 2% (15/700), 2% (19/771) and 3% (22/719) of patients in the 74Gy, 60Gy and 57Gy groups respectively at 10 years. The most common intervention reported was a sigmoidoscopy with 12% (79/681), 8% (60/739) and 9% (65/702) in the 74Gy, 60Gy and 57Gy groups respectively. Of those patients who underwent a sigmoidoscopy it was due to symptoms for 81% (63/78) 81% (48/59) and 85% (55/65) of patients in the 74Gy, 60Gy and 57Gy group respectively. Frequencies of all other pre-specified co-morbidities or related interventions (ureteric obstruction, bowel strictures, trans-urethral resection of prostate, urethrotomy, urethral dilatation or long term catheterisation or treatment of proctopathy with steroid, sucralfate, formalin, laser coagulation or rectal diversion) were

298 Background: People presenting with early-stage LPCa have several treatment options. There is therapeutic equipoise with lack of randomised evidence for superiority of radiotherapy or surgery. PACE-A aimed to determine if there is improved quality of life (QoL) following SBRT compared to surgery. Methods: PACE (NCT01584258) is a phase 3 open-label multiple-cohort RCT. In PACE-A, people with LPCa, T1-T2, Gleason≤3+4, PSA≤20ng/mL & suitable for surgery were randomised (1:1) to SBRT or surgery. SBRT dose was 36.25Gy/5 fractions in 1-2 weeks; surgery was laparoscopic or robotically assisted prostatectomy. Androgen deprivation was not permitted. Co-primary endpoints were patient reported outcomes (PROs) of Expanded Prostate Index Composite (EPIC-26) questionnaire number of absorbent pads per day & EPIC bowel subdomain score at 2 years. Target sample size was 234 participants (pts) to detect 9% difference in urinary incontinence (80% power, 5% 2-sided alpha) & 5-point difference in mean bowel subdomain score (90% power, 5% 2-sided alpha) with higher EPIC score (range 0-100) indicating better QoL. Secondary endpoints included clinician reported toxicity and additional PROs (1% significance level). Analysis is by treatment received. Results: From Aug 2012 to Feb 2022, 123 men from 10 UK centres were randomised. The IDMC advised stopping recruitment after a 2-year gap in during COVID. Pts had median age 66years (IQR: 61, 69), median PSA 8ng/ml (6, 11) with 52% tumours ≥T2b and 79% Gleason 3+4; 93% pts were of white race. 58/63 pts received SBRT as allocated (2 received surgery, 2 unknown, 1 withdrawn); 48/60 received surgery as allocated (1 received SBRT, 3 received CRT, 2 unknown, 6 withdrawn). 8 laparoscopic and 42 robotic assisted operations were performed. Median follow-up is 50 months (IQR 41, 74). At 2 years, fewer SBRT pts reported use of urinary pads: 2/43 (4.5%) vs 15/32 (46.9%), p

Several studies have demonstrated the association between acute and late radiotherapy toxicity in prostate cancer using older radiotherapy techniques. However, whether this association is present with newer techniques such as stereotactic body radiotherapy (SBRT), remains unclear. We use univariable and multivariable logistic regression to analyse the association between grade 2 or worse acute gastrointestinal (GI) and genitourinary (GU) toxicities with equivalent late toxicities in patients treated with SBRT and conventional or moderately fractionated radiotherapy (CRT) within the PACE-B study. 842 patients were included in this analysis. Common Terminology Criteria for Adverse Events (CTCAE) was the primary clinician reported outcome measure used in this analysis. In univariable analysis, experiencing a grade 2+ acute GU toxicity was significantly associated with developing a grade 2+ late GU toxicity after SBRT (OR 4.63, 95% CI (2.96–7.25), p < 0.0001) and CRT (OR 2.83, 95% CI (1.69–4.71), p < 0.0001). This association remained significant in multivariable analysis. In univariable analysis, experiencing a grade 2+ acute GI toxicity was also associated with developing a grade 2+ late GI toxicity after SBRT (OR 3.67, 95% CI (1.91–7.03), p < 0.0001) and CRT (OR 4.4, 95% CI (2.04–9.47), p < 0.0001). This association also remained significant in multivariable analysis. Grade 2+ baseline GU symptoms were also associated with grade 2+ late urinary toxicity in both univariable and multivariable analysis. Overall, acute toxicity is an important predictor variable for late GU/GI toxicity after localised prostate radiotherapy using SBRT and CRT. Future work should test whether optimising symptoms pre-treatment and early intervention in those with significant acute toxicities could mitigate the development late of toxicity.

Prostate bed radiotherapy is a standard treatment after radical prostatectomy. Recent evidence suggests that, for patients with a PSA 0.34 ng/ml, the radiotherapy treatment volume should include not only the prostate bed but also the pelvic lymph nodes. We describe the patterns of failure after prostate bed radiotherapy, focussing on the proportion of patients with radiologically confirmed pelvic nodal failure only, in the absence of distant disease.Patients included were men receiving prostate bed radiotherapy at the Royal Marsden Hospital between 1997 and 2013. The key outcome of interest was the pattern of radiologic failure after prostate bed radiotherapy. Baseline characteristics of patients experiencing pelvic nodal failure without distant disease were compared versus all other relapse patterns. Comparisons were by Chi-square test, with multiple testing adjusted p 0.005 significant.140 of 322 patients developed biochemical failure after salvage RT. Radiologic failure occurred in 89 patients. 35 of the 89 patients (39%) with radiologic failure had pelvic nodal failure without distant disease, with no significant differences in baseline characteristics when compared to all other patients. The rate of pelvic nodal failure was the same for patients with PSA above or below 0.34 ng/ml (16/149, 95% CI = 6-17% vs 19/171, 95% CI = 7-17%).Pelvic lymph node disease, without more distant disease, is a common site of failure in men receiving radiotherapy to the prostate bed, including those with PSA 0.34 ng/ml. This observation informs the case for including the pelvic lymph nodes in the radiotherapy treatment volume.

Androgen deprivation therapy (ADT) is an integral component in the management of prostate cancer across multiple disease states. Traditionally, luteinizing hormone-releasing hormone (LHRH) agonists constituted the backbone of ADT. However, gonadotropin-releasing hormone receptor hormone (GnRH) antagonists also are available, which offer faster testosterone suppression and reduced likelihood of ADT-related adverse effects compared with LHRH agonists, including the potential for fewer ADT-associated major cardiac events. Until recently, all forms of LHRH agonists and GnRH antagonist formulations were of parenteral administration. However, recently relugolix gained Food and Drug Administration approval as the first oral GnRH antagonist. Relugolix achieves faster and more complete testosterone suppression compared with an LHRH agonist. This translates to more rapid prostate-specific antigen response compared with LHRH agonists. After discontinuation of relugolix, testosterone recovers faster than after GnRH agonists or injectable GnRH antagonist therapy. Overall, these factors provide opportunities for more precisely defined ADT duration when combined with radiation therapy. The rapid onset and offset of testosterone suppression with relugolix may require physicians to rethink the mechanism and goals of ADT when prescribing. As an oral formulation, relugolix enables patients to avoid pain and injection site reactions, limit extra office visits for injections, and achieve a shorter duration of experiencing the side effects of castrate testosterone levels. This convenience and tolerability may enhance physicians' willingness to prescribe ADT and patients' feeling of control during their ADT course, but the potential advantages are accompanied by the risks of patients choosing to discontinue therapy to escape side effects of ADT. This article focuses on different aspects of what is known and unknown regarding the optimal use of ADT and radiation therapy, and how relugolix, due to its properties, fit into our current treatment paradigms for localized prostate cancer.

Radiation therapy (RT) continues to play an important role in the treatment of cancer. Adaptive RT (ART) is a novel method through which RT treatments are evolving. With the ART approach, computed tomography or magnetic resonance (MR) images are obtained as part of the treatment delivery process. This enables the adaptation of the irradiated volume to account for changes in organ and/or tumor position, movement, size, or shape that may occur over the course of treatment. The advantages and challenges of ART maybe somewhat abstract to oncologists and clinicians outside of the specialty of radiation oncology. ART is positioned to affect many different types of cancer. There is a wide spectrum of hypothesized benefits, from small toxicity improvements to meaningful gains in overall survival. The use and application of this novel technology should be understood by the oncologic community at large, such that it can be appropriately contextualized within the landscape of cancer therapies. Likewise, the need to test these advances is pressing. MR-guided ART (MRgART) is an emerging, extended modality of ART that expands upon and further advances the capabilities of ART. MRgART presents unique opportunities to iteratively improve adaptive image guidance. However, although the MRgART adaptive process advances ART to previously unattained levels, it can be more expensive, time-consuming, and complex. In this review, the authors present an overview for clinicians describing the process of ART and specifically MRgART.

PurposeDaily quantitative MR imaging during radiotherapy of cancer patients has become feasible with MRI systems integrated with linear accelerators (MR-linacs). Quantitative images could be used for treatment response monitoring. With intravoxel incoherent motion (IVIM) MRI, it is possible to acquire perfusion information without the use of contrast agents. In this multicenter study, daily IVIM measurements were performed in prostate cancer patients to identify changes that potentially reflect response to treatment.Materials and MethodsForty-three patients were included, treated with 20 fractions of 3 Gy on a 1.5 T MR-linac. IVIM measurements were performed on each treatment day. The diffusion coefficient (D), perfusion fraction (f), and pseudo-diffusion coefficient (D*) were calculated based on the median signal intensities in the non-cancerous prostate and the tumor. Repeatability coefficients (RCs) were determined based on the first two treatment fractions. Separate linear mixed-effects models were constructed for the three IVIM parameters.ResultsIn total, 726 fractions were analyzed. Pre-treatment average values, measured on the first fraction before irradiation, were 1.46 × 10−3 mm2/s, 0.086, and 28.7 × 10−3 mm2/s in the non-cancerous prostate and 1.19 × 10−3 mm2/s, 0.088, and 28.9 × 10−3 mm2/s in the tumor, for D, f, and D*, respectively. The repeatability coefficients for D, f, and D* in the non-cancerous prostate were 0.09 × 10−3 mm2/s, 0.05, and 15.3 × 10−3 mm2/s. In the tumor, these values were 0.44 × 10−3 mm2/s, 0.16, and 76.4 × 10−3 mm2/s. The mixed effects analysis showed an increase in D of the tumors over the course of treatment, while remaining stable in the non-cancerous prostate. The f and D* increased in both the non-cancerous prostate and tumor.ConclusionsIt is feasible to perform daily IVIM measurements on an MR-linac system. Although the repeatability coefficients were high, changes in IVIM perfusion parameters were measured on a group level, indicating that IVIM has potential for measuring treatment response.

Online magnetic resonance-guided radiotherapy (oMRgRT) represents one of the most innovative applications of current image-guided radiation therapy (IGRT). The revolutionary concept of oMRgRT systems is the ability to acquire MR images for adaptive treatment planning and also online imaging during treatment delivery. The daily adaptive planning strategies allow to improve targeting accuracy while avoiding critical structures. This ESTRO-ACROP recommendation aims to provide an overview of available systems and guidance for best practice in the implementation phase of hybrid MR-linac systems. Unlike the implementation of other radiotherapy techniques, oMRgRT adds the MR environment to the daily practice of radiotherapy, which might be a new experience for many centers. New issues and challenges that need to be thoroughly explored before starting clinical treatments will be highlighted.

External beam radiotherapy for prostate cancer is an optimal treatment choice for men with localised prostate cancer and is associated with long term disease control in most patients. Image-guided prostate radiotherapy is standard of care, however, current techniques can include invasive procedures with imaging of poor soft tissue resolution, thus limiting accuracy.MRI is the imaging of choice for local prostate cancer staging and in radiotherapy planning has been shown to reduce target volume and reduce inter-observer prostate contouring variability. The ultimate aim would be to have a MR-only workflow for prostate radiotherapy.Within this article, we discuss these opportunities and challenges, relevant due to the increasing availability of MR-guided radiotherapy. Prospective multi-centre studies are underway to determine the feasibility of MR-guided prostate radiotherapy and daily adaptive replanning. In parallel, development and adaptation of the existing radiotherapy multidisciplinary workforce is essential to enable an efficient and effective MR-guided radiotherapy workflow. This technology potentially provides us with the anatomical and biological information to further improve outcomes for our patients. Keywords: Prostate cancer, Radiotherapy, MRI, Daily adaptive replanning

Purpose There are sparse data describing outcomes of bone-only oligometastatic prostate cancer in comparison with lymph node disease treated with stereotactic body radiotherapy (SBRT). The primary aim of this study was to report progression-free survival (PFS) data for patients with bone-only disease. Influence of hormone sensitivity and androgen deprivation therapy use was also assessed. Methods This is a single-centre retrospective cohort study. Hormone-sensitive and castrate-resistant patients with oligometastatic (≤ 3) bone-only prostate cancer treated with SBRT were included. Data were collected using electronic records. Kaplan–Meier survivor function, log rank test, as well as Cox regression were used to calculate PFS and overall survival. Results In total, 51 patients with 64 bone metastases treated with SBRT were included. Nine patients were castrate resistant and 42 patient’s hormone sensitive at the time of SBRT. Median follow-up was 23 months. Median PFS was 24 months in hormone-sensitive patients and 3 months in castrate-resistant patients. No patients experienced grade 3 or 4 toxicities. There were three in-field recurrences. Conclusions In this study, patients with bone oligometastatic disease showed potential benefit from SBRT with a median PFS of 11 months. Hormone-sensitive patients showed the greatest benefit, with results similar to that published for oligometastatic pelvic nodal disease treated with SBRT. Prospective randomised control trials are needed to determine the survival benefit of SBRT in oligometastatic bone-only prostate cancer and to determine prognostic indicators. Electronic supplementary material The online version of this article (10.1007/s00345-019-02873-w) contains supplementary material, which is available to authorized users.

The pattern of metastases in prostate cancer (PC) is evolving. Increased use of imaging, newer imaging techniques with higher sensitivity for disease detection and patients receiving multiple lines of novel therapies with increased life expectancy are likely to be contributory. Awareness of metastatic disease patterns improves early diagnosis, accurate staging, and initiation of appropriate therapy, and can inform prognostic information and anticipate potential disease complications. The aim of this review is to document the spectrum of metastases in PC including emerging and unusual patterns, and to highlight the role of novel imaging including prostate-specific membrane antigen (PSMA)-positron-emission tomography (PET) and whole-body magnetic resonance imaging (WB-MRI) to improve diagnostic and response assessment accuracy.

Purpose: MR-guided Radiation Therapy (MRgRT) allows for high-precision radiotherapy under real-time MR visualization. This enables margin reduction and subsequent dose escalation which may lead to higher tumor control and less toxicity. The Unity MR-linac (Elekta AB, Stockholm, Sweden) integrates a linear accelerator with a 1.5T diagnostic quality MRI and an online adaptive workflow. A prospective international registry was established to facilitate the evidence-based implementation of the Unity MR-linac into clinical practice, to systemically evaluate long-term outcomes, and to aid further technical development of MR-linac-based MRgRT. Methods and Results: In February 2019, the Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac study (MOMENTUM) started within the MR-linac Consortium. The MOMENTUM study is an international academic-industrial partnership between several hospitals and industry partner Elekta. All patients treated on the MR-linac are eligible for inclusion in MOMENTUM. For participants, we collect clinical patient data (e.g., patient, tumor, and treatment characteristics) and technical patient data which is defined as information generated on the MR-linac during treatment. The data are captured, pseudonymized, and stored in an international registry at set time intervals up to two years after treatment. Patients can choose to provide patient-reported outcomes and consent to additional MRI scans acquired on the MR-linac. This registry will serve as a data platform that supports multicenter research investigating the MR-linac. Rules and regulations on data sharing, data access, and intellectual property rights are summarized in an academic-industrial collaboration agreement. Data access rules ensure secure data handling and research integrity for investigators and institutions. Separate data access rules exist for academic and industry partners. This study is registered at ClinicalTrials.gov with ID: NCT04075305 (https://clinicaltrials.gov/ct2/show/NCT04075305). Conclusion: The multi-institutional MOMENTUM study has been set up to collect clinical and technical patient data to advance technical development, and facilitate evidenced-based implementation of MR-linac technology with the ultimate purpose to improve tumor control, survival, and quality of life of patients with cancer.

Introduction The role of the Urology Specialist Therapeutic Radiographer (USTR) was introduced to support a busy NHS uro-oncology practice. Key objectives were to improve patient preparedness for and experience of radiotherapy, focussed on prostate cancer. Pre-radiotherapy information seminars were developed, and on-treatment patient review managed by the USTRs. To evaluate the revamped patient pathway and direct further improvements, a patient experience survey was designed. Methods An 18-point patient questionnaire was produced. The questionnaire captured patient experience and preparedness; pre, during and at completion of treatment. The patient population comprised men receiving radiotherapy for primary prostate cancer within one UK Trust. Results Two-hundred and fifty-one responses were received. Seventy-three percent of patients felt completely prepared for radiotherapy, higher in those who attended a seminar (77%) compared to those who did not (61%). Eighty-nine and eighty-six percent of respondents were completely satisfied with verbal and written information received prior to commencing radiotherapy respectively. Seventy-three percent of responders would have found additional resources helpful. With respect to on-treatment clinics; eighty-five percent were seen on time or within 20 minutes, eighty-three percent felt fully involved in decisions regarding their care and ninety-one percent reported complete satisfaction with the knowledge of the health care professional reviewing them. The follow-up process was completely understood by eighty-eight percent and overall patient experience rated excellent by eighty-five percent of responders. Conclusion The revamped pathway implemented by USTRs has achieved high levels of satisfaction at all stages of the prostate patient's radiotherapy. By diversifying the format of information giving, the USTRs hope to further meet the information needs of patients. Implications for practice Validation of a prostate cancer radiotherapy pathway which employs USTRs and utilises a patient preparation seminar. This model could support the introduction of Specialist Therapeutic Radiographers in other Trusts and treatment sites.

There has been growing interest in oligometastatic prostate cancer (OMPC) with a mounting body of evidence to suggest that it is a distinct disease state, both biologically and prognostically, when compared to polymetastatic prostate cancer. Three subgroups have been recognised; de novo synchronous, metachronous/oligorecurrent and oligoprogressive disease. The belief that patients with OMPC can be treated more aggressively to improve survival is transforming patient care. Identifying these patients poses the first challenge, and we explore the imaging modalities currently utilised and those that are promising. For patients with de novo synchronous OMPC, both early systemic treatment in addition to androgen deprivation therapy (ADT) and radiotherapy to the prostate increase overall survival (OS), and both are increasingly being integrated into routine clinical practice. Metastasis-directed therapy (MDT) has predominantly been delivered using stereotactic body radiotherapy (SBRT) in prostate cancer and studies have shown SBRT is well-tolerated, provides excellent local control and can be used to delay ADT in the metachronous setting. We discuss the current management strategies in OMPC, review the evidence supporting the use of SBRT and outline ongoing trials.