Purpose/Objective(s) Dose in LDR prostate brachytherapy is routinely prescribed to the global prostate which has correlated with outcome in some studies but not in others. Dose to prostate sectors has wide variation with anterior base sectors typically receiving a lower dose. To date no study has examined dose to the dominant intraprostatic lesion (DIL) sector to see if it predicted freedom from biochemical/clinical failure (BCF). Materials/Methods We examined a cohort of 606 patients treated with LDR brachytherapy (145Gy monotherapy n = 546; 110Gy combination n = 60) in a single institution from 2009-20 (13% low, 80% intermediate, 7% NCCN high-risk). The prostate sector(s) in which the DIL was located, was/were identified following review of the diagnostic MRI (n = 599) and pathology report (n = 606). Outcomes were blinded during this process. The prostate was divided into 12 sectors; 3 equal thirds (base/midgland/apex), and 4 axial sectors by two separate methods; plus (“+”) and cross shape (“x”). Kaplan-Meier curves were generated with the log-rank test performed to assess for differences in BCF rates. Results Relative to the global prostate gland (D90 108.0%, IQR 101.8-114.3%), the anterior base received the lowest median (IQR) D90 (85.9%, 76.6-95.6%) and the right and posterior midgland received the highest median D90; 142.2% (131.1-153.7%) and 141.8% (128.3-155.5%) respectively. 5-year BCF for the entire cohort was 89.6%. Using cross-shaped prostate sector division, freedom from BCF was significantly lower when the DIL was located in the left and right base (71.3%, p = 0.0004 and 75.0%, p = 0.001 respectively) and higher when the DIL was located in the posterior midgland (96.8%, p = 0.002) with HR = 0.4 (95% CI = 0.2-0.7) relative to when the DIL was located elsewhere. Using plus-shaped prostate sector division, the anterior right and left base sectors had significantly lower BCF event free rates (76.7%, p = 0.004 and 49.1%, p = 0.0002 respectively) with respective HR = 5.4 (1.7-17.0) and 9.6 (2.9-31.3). Conclusion This is the first LDR brachytherapy study to analyze biochemical outcomes according to the location of the DIL. The lower BCF event free rates when the DIL was located in the anterior base may be due to the lower dose received due to its anatomical location, which can be difficult to implant due to pubic arch interference and proximity to the bladder neck, resulting in lower planned dose to this region. These findings reinforce the importance of considering the location of the DIL when determining the suitability of patients for prostate brachytherapy. The higher BCF event free rates where the DIL was located in the posterior midgland may be related to the higher dose delivered to this sector relative to the global prostate gland. These findings suggest dose-escalation to the DIL in LDR prostate brachytherapy may improve patient outcomes in the treatment of prostate cancer.

Purpose: The aim of this study was to establish the feasibility of a randomized clinical trial comparing SABR with prostateonly (P-SABR) or with prostate plus pelvic lymph nodes (PPN-SABR) in patients with unfavorable intermediate- or high-risk localized prostate cancer and to explore potential toxicity biomarkers.Methods and Materials: Thirty adult men with at least 1 of the following features were randomized 1:1 to P-SABR or PPNSABR: clinical magnetic resonance imaging stage T3a N0 M0, Gleason score >= 7 (4+3), and prostate-specific antigen >20 ng/mL. P-SABR patients received 36.25 Gy/5 fractions/29 days, and PPN-SABR patients received 25 Gy/5 fractions to pelvic nodes, with the final cohort receiving a boost to the dominant intraprostatic lesion of 45 to 50 Gy. Phosphorylated gammaH2AX (gH2AX) foci numbers, citrulline levels, and circulating lymphocyte counts were quantified. Acute toxicity information (Common Terminology Criteria for Adverse Events, version 4.03) was collected weekly at each treatment and at 6 weeks and 3 months. Physician-reported late Radiation Therapy Oncology Group (RTOG) toxicity was recorded from 90 days to 36months postcompletion of SABR. Patient-reported quality of life (Expanded Prostate Cancer Index Composite and Interna-tional Prostate Symptom Score) scores were recorded with each toxicity time point.Results: The target recruitment was achieved, and treatment was successfully delivered in all patients. A total of 0% and 6.7% (P-SABR) and 6.7% and 20.0% (PPN-SABR) experienced acute grade >= 2 gastrointestinal (GI) and genitourinary (GU) toxicity, respectively. At 3 years, 6.7% and 6.7% (P-SABR) and 13.3% and 33.3% (PPN-SABR) had experienced late grade >= 2 GI and GU toxicity, respectively. One patient (PPN-SABR) had late grade 3 GU toxicity (cystitis and hematuria). No other grade >= 3 toxicity was observed. In addition, 33.3% and 60% (P-SABR) and 64.3% and 92.9% (PPN-SABR) experienced a minimally clin-ically important change in late Expanded Prostate Cancer Index Composite bowel and urinary summary scores, respectively. yH2AX foci numbers at 1 hour after the first fraction were significantly higher in the PPN-SABR arm compared with the P-SABR arm (P = .04). Patients with late grade >= 1 GI toxicity had significantly greater falls in circulating lymphocytes (12 weeks post-radiation therapy, P = .01) and a trend toward higher yH2AX foci numbers (P = .09) than patients with no late toxicity. Patients with late grade >= 1 bowel toxicity and late diarrhea experienced greater falls in citrulline levels (P = .05).Conclusions: A randomized trial comparing P-SABR with PPN-SABR is feasible with acceptable toxicity. Correlations of yH2AX foci, lymphocyte counts, and citrulline levels with irradiated volume and toxicity suggest potential as predictive bio-markers. This study has informed a multicenter, randomized, phase 3 clinical trial in the United Kingdom. (c) 2023 Elsevier Inc. All rights reserved.

Supplementary figure SF1 shows CONSORT diagram of trial profile

Supplementary table ST1 shows adverse events in all domains other than GI, GU and haematological

Supplementary figure SF4 shows (A) Kaplan-Meier plot to estimate median progression free survival as time from first docetaxel (or trial registration if no docetaxel received) until PSA progression per PCWG. Median progression free survival = 20.5 months. (B) Kaplan Meier plot to estimate median overall survival as time from first docetaxel (or trial registration if no docetaxel received) until death. Median not reached.

Supplementary figure SF2 shows mean EPIC score by domain by timepoint. Error bars = 95% confidence intervals.

Supplementary figure SF3 shows examples of WB-MRI pre and post 6 cycles of radium-223 and pelvic radiotherapy. A and B showing tumour burden reduction in femora, C and D showing tumour burden reduction in lumbosacral spine and E and F showing tumour burden increase in thoracic spine.

Patients with localized prostate cancer are often faced with a myriad of treatment options; it is our duty as cancer clinicians to partner with them to make an informed choice based on an objective assessment of the available evidence and their own values and priorities. This shared decision making is best achieved by ensuring that patients consult with the clinicians who deliver each treatment, be they surgeons, radiation oncologists, or brachytherapists. To do this effectively, we need robust evidence. As clinicians, we often focus on data from randomized controlled trials (RCTs), an approach validated by the landmark Prostate Testing for Cancer and Treatment (ProtecT) trial,1Hamdy F.C. Donovan J.L. Lane J.A. et al.10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer.N Engl J Med. 2016; 375: 1415-1424Crossref PubMed Scopus (1605) Google Scholar which showed comparable survival in patients treated with surgery or radiation therapy despite multiple observational trials, inability to fully account for gatekeeper bias, or findings to the contrary. However, as we enter the era of genomic stratification, functional imaging, and big data, RCTs become more challenging to carry out, and the quality of real-world observational data sets is rapidly improving. The National Prostate Cancer Audit (NPCA) combines English cancer registry data, a mandatory reported radiation therapy data set, hospital admission statistics, and a national patient survey with diagnostic and procedural coding as a surrogate for toxicity, creating a large contemporary data set for analysis that has already yielded important real-world evidence.2Nossiter J. Sujenthiran A. Cowling T.E. et al.Patient-reported functional outcomes after hypofractionated or conventionally fractionated radiation for prostate cancer: A national cohort study in England.J Clin Oncol. 2020; 38: 744-752Crossref PubMed Scopus (10) Google Scholar In this issue, the NPCA data set has been interrogated by Parry et al3Parry MG, Nossiter J, Sujenthiran A, et al. Impact of high-dose rate and low-dose rate brachytherapy boost on toxicity, functional and cancer outcomes in patients receiving external beam radiation therapy for prostate cancer: A national population-based study. Int J Radiat Oncol Biol Phys. https://doi.org/10.1016/j.ijrobp.2020.11.023. Accessed December 31, 2020.Google Scholar to fan the flames of debate on the risk versus benefit of combination therapy. Although escalating radiation dose in the management of intermediate- and high-risk prostate cancer has an irrefutable benefit in terms of biochemical outcomes, the best method to achieve such escalation remains unclear. Proponents of the combination of external beam radiation therapy (EBRT) with low- or high-dose-rate brachytherapy boost (LDR-BB or HDR-BB) point to the level 1 evidence of improved biochemical failure-free survival with their approach compared with EBRT alone.4Morris W.J. Tyldesley S. Rodda S. et al.Androgen suppression combined with elective nodal and dose escalated radiation therapy (the ASCENDE-RT Trial): An analysis of survival endpoints for a randomized trial comparing a low-dose-rate brachytherapy boost to a dose-escalated external beam boost for high- and intermediate-risk prostate cancer.Int J Radiat Oncol Biol Phys. 2017; 98: 275-285Abstract Full Text Full Text PDF PubMed Scopus (447) Google Scholar,5Hoskin P.J. Rojas A.M. Bownes P.J. et al.Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer.Radiother Oncol. 2012; 103: 217-222Abstract Full Text Full Text PDF PubMed Scopus (372) Google Scholar However, the balance between dose and toxicity is finely poised, as reflected in both the Androgen Suppression Combined With Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) companion publication on morbidity after combination LDR-BB versus EBRT6Rodda S. Tyldesley S. Morris W.J. et al.ASCENDE-RT: An analysis of treatment-related morbidity for a randomized trial comparing a low-dose-rate brachytherapy boost with a dose-escalated external beam boost for high- and intermediate-risk prostate cancer.Int J Radiat Oncol Biol Phys. 2017; 98: 286-295Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar and the report from Hoskin et al.5Hoskin P.J. Rojas A.M. Bownes P.J. et al.Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer.Radiother Oncol. 2012; 103: 217-222Abstract Full Text Full Text PDF PubMed Scopus (372) Google Scholar At a median follow-up of 4.4 to 4.6 years, Parry et al3Parry MG, Nossiter J, Sujenthiran A, et al. Impact of high-dose rate and low-dose rate brachytherapy boost on toxicity, functional and cancer outcomes in patients receiving external beam radiation therapy for prostate cancer: A national population-based study. Int J Radiat Oncol Biol Phys. https://doi.org/10.1016/j.ijrobp.2020.11.023. Accessed December 31, 2020.Google Scholar noted that the relatively small brachytherapy boost cohorts of 330 LDR-BB patients (0.6% of patients) and 2765 HDR-BB patients (5.1% of patients) had more grade 2 or higher genitourinary toxicity (15.8% and 16.6%, respectively) than the 51,547 EBRT patients (10.4%) and that the men treated with LDR-BB also had more grade 2 or higher gastrointestinal (GI) toxicity (32.3%) than the cases treated with either HDR-EBRT or EBRT monotherapy (16.7% and 18.7%, respectively). Toxicity levels of grade 3 or greater were distributed similarly to the results for grade 2 or greater but were relatively low. Importantly, patient-reported functional outcomes from mailed questionnaires in a subset of the population corroborated the coded toxicity outcomes. As acknowledged by the authors, significant limitations exist, including a lack of data on the use and duration of androgen deprivation, radiation therapy dose, volume and margin variability, and biochemical outcomes. The reported improvement in prostate cancer–specific mortality with HDR-RT compared with EBRT alone will undoubtedly bolster the combination therapy advocates but should be interpreted with caution because follow-up was short; the effect was observed as early as 2 years after treatment began, and mortality data relied on death certificates mentioning prostate cancer as part of the sequence leading to death. Two points are clear from both RCTs and observational data sets: higher dose delivered with combination regimens achieves better biochemical control, but combination regimens result in greater toxicity. Outdated imaging technology, better case selection, and implanter experience are a few of the reasons cited as to why toxicity levels should be lower now and why combination therapy should remain part of the armory for treating prostate cancer. Technology has inevitably moved on in the 5 to 10 years since these men were treated, and advances such as bioabsorbable perirectal hydrogels7Mariados N. Sylvester J. Shah D. et al.Hydrogel spacer prospective multicenter randomized controlled pivotal trial: Dosimetric and clinical effects of perirectal spacer application in men undergoing prostate image guided intensity modulated radiation therapy.Int J Radiat Oncol Biol Phys. 2015; 92: 971-977Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar provide a clear reduction in the dose-volume parameters for the rectum, with expanding clinical and patient-reported outcome data confirming clinical benefit in all 3 domains of bowel, urinary, and sexual function. Such advances applied to equivalent patient groups today could be anticipated to provide a significant reduction in bowel toxicity, and clearly, the largest absolute reduction of reported GI procedures and interventions would be seen in combination LDR-BB cases. Combined-therapy protocols have been quick to investigate and adopt hydrogel technology.8Ardenkani M.A. Ghaffari H. Optimization of prostate brachytherapy techniques with polyethylene glycol based hydrogel spacers: A systematic review.Brachytherapy. 2019; 19: 13-23Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar In addition, the research into image guided ultrahypofractionated regimens such as the 25 Gy in 5 fractions of stereotactic radiation therapy and brachytherapy boost9Kollmeier M.A. McBride S. Varghese M. et al.Low-dose-rate brachytherapy combined with ultrahypofractionated radiation therapy for clinically localized, intermediate-risk prostate cancer: Results from a prospective trial.Int J Radiat Oncol Biol Phys. 2020; 108: 905-913Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar seek to keep pace with the increasingly convenient hypofractionated and ultrahypofractionated EBRT monotherapy schedules that are capitalizing on the difference in α/β ratio between bowel and tumor. Combining the conformality and rapid dose falloff of brachytherapy with EBRT will always provide a more biologically effective dose than EBRT monotherapy can achieve alone. Functional imaging with prostate-specific membrane antigen positron emission tomography/computed tomography will clearly expand into the primary staging arena, directing men more appropriately to systemic therapy with or without radiation for advanced disease and more precise case selection for dose escalation in high-risk localized/locally advanced disease. In addition, the advances in magnetic resonance imaging now permit accurate targeting of disease at transperineal biopsy and subsequent delineation of the dominant intraprostatic lesion (DIL) for dose-escalated boost. This strategy is being explored in the ongoing PIVOTALboost study10Syndikus I. Cruickshank C. Staffurth J. et al.PIVOTALboost: A phase III randomised controlled trial of prostate and pelvis versus prostate alone radiotherapy with or without prostate boost (CRUK/16/018).Clin Transl Radiat Oncol. 2020; 25: 22-28Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar with prostate ± pelvis randomization and a further subset with or without DIL boost, which importantly allows the boost to be delivered with either EBRT or HDR treatment. The study is recruiting well and in time is expected to contribute to randomized data for the toxicity and outcome debate on, first, EBRT versus HDR-RT, and second, elective nodal irradiation. The potential move from whole-gland boost to focal or ultrafocal boost will appeal to radiation oncologists and brachytherapists alike. Deploying available technology to create dose heterogeneity will allow radiation oncologists to increase the dose in the DIL to levels that would be limited by organ-at-risk constraints if applied to the whole gland. Brachytherapists may seek to maintain the high dose they can obtain in the DIL but perhaps de-escalate to surrounding tissues. Finally, as clinicians, we have a duty to weigh the available research and experience that we have to then generate and contribute to high-quality informative clinical studies and honestly guide our patients to an individualized treatment plan that optimizes the balance of toxicity and quality of life against disease outcomes.

248 Background: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat low/intermediate risk localised prostate cancer (PCa). However, data on SABR +/- pelvic nodal irradiation (PNI) in high-risk disease is limited to single institution, single-arm studies. The Stereotactic Prostate Radiotherapy (SPORT) trial examined the feasibility of delivering a randomised trial of SABR ± PNI. The composite primary endpoint to determine feasibility comprised: recruitment rate, technical feasibility, acute toxicity (CTCAE v4.0) and quality of life (QoL)(EPIC). Secondary and exploratory endpoints including late toxicity (RTOG) and QoL and potential biomarkers of toxicity (plasma citrulline and DNA damage in circulating lymphocytes) are also presented. Methods: Men with localised PCa demonstrating one of T3a, Gleason score ≥4+3 or PSA>20 were eligible. T3b and T4 disease were excluded. 30 participants were randomised 1:1 to prostate SABR (P-SABR) or prostate and pelvis SABR (PPN-SABR). The prostate and proximal 1-2cm seminal vesicles received 36.25 Gy in 5 fractions over 29 days (prostate CTV 40Gy). The PPN-SABR arm also received 25 Gy in 5 fractions to the pelvic nodes. All patients had fiducial markers and a rectal spacer gel in-situ. As initial toxicity rates were low, the final 10 men received an additional integrated boost to the dominant intraprostatic lesion of up to 50 Gy, irrespective of randomisation. Results: Feasibility was demonstrated. The target recruitment of 30 men was met (83% high risk). Treatment, including an integrated boost plus PNI, was achievable using strict normal tissue constraints. Acute toxicity and QoL were acceptable (Table: Grade≥2 GU 7%, 27% and GI 0%, 7%; minimal clinically important change (MCIC) in EPIC urinary 40%, 60% and bowel score 33%, 47% in P and PPN arms respectively). At median follow up of 30 months (range 18-42 months), late toxicity and QoL were acceptable (Grade≥2 GU 7%, 20% and GI 0%, 13%; MCIC in EPIC urinary 33%, 67% and bowel score 33%, 67% in P and PPN arms respectively). All toxicity was ≤ grade 2 with the exception of one late grade 3 GU toxicity occurring in the PPN arm. Serum citrulline, a marker of small bowel function, trended towards lower levels in the PPN arm, in keeping with a significantly higher dose delivered to the small bowel in this arm. DNA damage foci in circulating lymphocytes increased at 1 hour after radiation. Foci count and repair correlated to toxicity measures will be presented. Conclusions: A randomised clinical trial comparing P-SABR to PPN-SABR is feasible. There was a suggestion of increased toxicity with PPN-SABR, but this remained acceptable. This data will inform a UK multi-centre phase 2 study. Clinical trial information: NCT03253978 . [Table: see text]

AbstractPurpose: Radium-223 is an alpha-emitting radionuclide associated with overall survival (OS) improvement in metastatic castration-resistant prostate cancer (mCRPC). External beam radiotherapy (EBRT) to prostate extends OS in men with metastatic hormone-sensitive prostate cancer (mHSPC) limited to less than 4 metastases. We hypothesized that combination radium-223 + pelvic EBRT could safely deliver maximal radiotherapy doses to primary and metastatic prostate cancer and may improve disease control. Patients and Methods: Thirty patients with de novo bone metastatic mHSPC who had commenced androgen deprivation therapy (ADT) and docetaxel were recruited to this single-arm, open-label, prospective clinical trial: Neo-adjuvant Androgen Deprivation Therapy, Pelvic Radiotherapy and RADium-223 (ADRRAD; for new presentation T1–4 N0–1 M1B adenocarcinoma of prostate). Study treatments were: ADT, 6 cycles of radium-223 q28 days, conventionally fractionated prostate radiotherapy (74 Gy) and simultaneous integrated boost to pelvic lymph nodes (60 Gy). Results: No grade 4/5 toxicity was observed. Three patients experienced grade 3 leukopenia, and 1 each experienced grade 3 neutropenia and thrombocytopenia; all were asymptomatic. One patient each experienced grade 3 dysuria and grade 3 urinary infection. No grade 3 gastrointestinal (GI) toxicity was observed. On treatment completion, there was a signal of efficacy; 24 (80%) patients had whole-body MRI evidence of tumor response or stability. Twenty-seven (90%) patients showed a reduction in alkaline phosphatase (ALP) compared with pretreatment levels. Median progression-free survival was 20.5 months. Conclusions: This is the first trial of combination ADT, radium-223, and EBRT to pelvis, post docetaxel. The combination was safe, with an efficacy signal. Multicenter randomized controlled trials (RCT) are warranted.

PURPOSE:Small cell carcinoma of the bladder (SCCB) is rare, accounting for less than 1% of all bladder carcinomas. It is aggressive, and outcomes are poor as a result of its early metastatic spread. Owing to its rarity, there are limitations on data to propose standardized management pathways. METHODS AND MATERIALS:We conducted a retrospective analysis of patients presenting with pure or predominant-histology SCCB to 26 institutions in the United Kingdom between 2006 and 2016. The data cutoff date was February 1, 2018. We report patient characteristics, treatment received, and subsequent clinical outcomes. RESULTS:A total of 409 eligible patients were included. Among these, 306 (74.8%) were male, the median age was 71 years (range, 35-96 years), and 189 patients (46.2%) had pure-histology SCCB. At data cutoff, 301 patients (73.6%) had died. The median overall survival (OS) was 15.9 months (95% CI, 13.2-18.7 months). Two hundred patients (48.9%) were confirmed to have bladder-confined disease (N0, M0), with a median OS of 28.3 months (95% CI, 20.9-35.8 months), versus a median OS of 12.7 months (95% CI, 10.9-14.6 months) for the 172 patients (42.1%) with confirmed N1-3 and/or M1 disease (hazard ratio [HR], 2.03; 95% CI, 1.58-2.60; P < .001). A total of 247 patients (61.5%) received primary chemotherapy, with a median OS of 21.6 months (95% CI, 15.5-27.6 months), versus a median OS of 9.1 months (95% CI, 5.4-12.8 months) in patients who did not receive primary chemotherapy (HR, 0.46; 95% CI, 0.37-0.59; P < .001). Choice of chemotherapy agent did not alter outcomes. For those with bladder-confined disease, 61 (30.5%) underwent cystectomy, and 104 (52.0%) received radiation therapy. Survival outcomes were similar for both cystectomy and radiation therapy. Only 6 patients (1.5%) were identified as having brain metastases at any time point. CONCLUSIONS:To our knowledge, this is the largest retrospective study of all-stage SCCB to date. Patients have a poor prognosis overall, but survival is improved in those able to receive chemotherapy and with organ-confined disease. Brain metastases are rare.

Purpose: Relapsed or progressive prostate cancer frequently manifests as consecutive PSA rises long before disease is clinically detectable. Imaging with novel radiotracers targeting prostate-specific membrane antigen (PSMA) has been shown to be more sensitive in identifying the site of disease at lower PSA levels compared with conventional imaging, which may provide increased opportunity for salvage therapy, more aggressive local management of oligometastatic disease or increased confidence in proceeding with systemic therapy [1]. We review the impact on the management of a cohort of our patients who have had a PSMA PET-CT.

73 Background: Plasma levels of citrulline, an amino acid, are derived mainly from small bowel enterocytes. Decreased levels occur in a range of bowel conditions and citrulline has been proposed as a biomarker of bowel toxicity in pelvic radiotherapy. In a prospective study, we identify no correlation between plasma citrulline and toxicity in men receiving prostate stereotactic radiotherapy randomized to receive either pelvic nodal irradiation or not. Furthermore, citrulline levels were not significantly different between these two groups. Methods: As part of an approved clinical trial, men with intermediate to high risk prostate cancer were randomised 1:1 to prostate only or prostate + pelvic nodal radiotherapy, delivered with a rectal spacer gel in situ. The prostate and proximal seminal vesicles received 40 Gy in 5 fractions. Those randomised to the pelvic nodal arm also received 25 Gy in 5 fractions to pelvic nodes. Citrulline was measured at 10 points during treatment – consent, before fraction 1, 1 and 24 hours following fraction 1, prior to each fraction 2 – 5 and at 6 weeks’ and 3 months’ follow up. Bowel toxicity was measured by EPIC patient reported scores. Results: 16 men with follow up of at least 3 months (median 9, maximum 18 months) were analysed. Reported toxicity was significantly higher in the prostate and pelvis arm: 5 of 9 men showed a decrease in EPIC bowel domain summary score of 10 points or more compared to 0 of 7 in the prostate-only arm (p = 0.0337, two tailed Fisher’s exact test). No significant correlation between toxicity and citrulline levels was seen, nor did citrulline vary significantly between arms or fall as treatment progressed. Data analysis for a further 8 men already recruited to the study is ongoing. Conclusions: Toxicity was more commonly reported by men randomised to receive pelvic radiotherapy, suggesting that the small bowel irradiated in pelvic fields plays a role in bowel toxicity experienced during stereotactic radiotherapy. Citrulline levels showed no significant correlation with toxicity or radiation dose to small bowel. We propose that citrulline is not a useful biomarker of small bowel toxicity in this setting. Clinical trial information: NCT03253978.