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Background ASCO/CCO guidelines recommend brachytherapy boost for intermediate-risk (IR) or high-risk (HR) prostate cancer (PCa) patients. Stereotactic ablative body radiotherapy (SABR) is an emerging technique for PCa but its use in HR disease is limited. We compare efficacy, toxicity, and quality-of-life (QoL) in patients treated on 2 prospective protocols that used SABR boost or MR-guided HDR brachytherapy boost (MR-HDR) with 6-18 months of androgen deprivation therapy (ADT). Methods In XXXXXX study (study 1), patients received 40Gy to prostate and 25Gy to pelvis in 5 weekly fractions. In XXXXXX (study 2), patients received HDR-BT 15Gy x 1 to the prostate and ≤22.5Gy to the MRI nodule, followed by 25Gy in 5 weekly fractions to pelvis. All patients received between 6 and 18 months of androgen deprivation therapy. Results Thirty patients (NCCN 7% unfavorable IR, and 93% HR) completed study 1 while 31 patients (NCCN 3% favorable IR, 47% Unfavorable IR and 50% HR) completed treatment as per study 2. Median follow-up was 72 and 62 months, respectively. In study 2, 6 patients had BF and all 6 developed metastatic disease. Actuarial 5-year BF was 0% for study 1 and 18.2% for study 2 (p=0.005). There was no significant difference in worst acute or late GI or GU toxicity. Grade 3 late GU toxicity was noted in 3% of the patients in study 2 (HDR-BT boost). There was no significant difference in QoL or minimally clinical important change. Conclusions In the context of 5-fraction pelvic radiotherapy and ADT, there does not appear to be a significant difference in toxicity or QoL between SABR vs. HDR BT boost. While efficacy favored the SABR boost cohort, this should be viewed in the context of limitations and biases associated with comparing two sequential phase II studies.

Purpose Integrating magnetic resonance (MR) into radiotherapy planning has several advantages. This report details the clinical implementation of an MR simulation (MR-planning) program for external beam radiotherapy (EBRT) in one of North America's largest radiotherapy programs. Methods and materials An MR radiotherapy planning program was developed and implemented at Sunnybrook Health Sciences Center in 2016 with two dedicated wide-bore MR platforms (1.5 and 3.0 Tesla). Planning MR was sequentially implemented every 3 months for separate treatment sites, including the central nervous system (CNS), gynecologic (GYN), head and neck (HN), genitourinary (GU), gastrointestinal (GI), breast, and brachial plexus. Essential protocols and processes were detailed in this report, including clinical workflow, optimized MR-image acquisition protocols, MR-adapted patient setup, strategies to overcome risks and challenges, and an MR-planning quality assurance program. This study retrospectively reviewed simulation site data for all MR-planning sessions performed for EBRT over the past 5 years. Results From July 2016 to December 2021, 8798 MR-planning sessions were carried out, which corresponds to 25% of all computer tomography (CT) simulations (CT-planning) performed during the same period at our institution. There was a progressive rise from 80 MR-planning sessions in 2016 to 1126 in 2017, 1492 in 2018, 1824 in 2019, 2040 in 2020, and 2236 in 2021. As a result, the relative number of planning MR/CT increased from 3% of all planning sessions in 2016 to 36% in 2021. The most common site of MR-planning was CNS (49%), HN (13%), GYN (12%), GU (12%), and others (8%). Conclusion Detailed clinical processes and protocols of our MR-planning program were presented, which have been improved over more than 5 years of robust experience. Strategies to overcome risks and challenges in the implementation process are highlighted. Our work provides details that can be used by institutions interested in implementing an MR-planning program.

Introduction: This clinical practice guideline is based on a systematic review to assess the use of multiparametric magnetic resonance imaging (mpMRI) in the diagnosis of clinically significant prostate cancer (csPCa) for biopsy-naive men and men with a prior negative transrectal ultrasound-guided systematic biopsy (TRUS-SB) at elevated risk. Methods: The methods of the clinical practice guideline included searches to September of 2020 of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Internal and external reviews were conducted. Results: The recommendations are: Recommendation 1: For biopsy-naive patients at elevated risk of csPCa, mpMRI is recommended prior to biopsy in patients who are candidates for curative management with suspected clinically localized prostate cancer. - If the mpMRI is positive, mpMRI-targeted biopsy (TB) and TRUS-SB should be performed together to maximize detection of csPCa. - If the mpMRI is negative, consider forgoing any biopsy after discussion of the risks and benefits with the patient as part of shared decision-making and ongoing followup. Recommendation 2: In patients who had a prior negative TRUSSB and demonstrate a high risk of having csPCa in whom curative management is being considered: - mpMRI should be performed. - If the mpMRI is positive, targeted biopsy should be performed. Concomitant TRUS-SB can be considered depending on the patient’s risk profile and time since prior TRUS-SB biopsy. - If the mpMRI is negative, consider forgoing a TRUS-SB only after discussion of the risks and benefits with the patient as part of shared decision-making and ongoing followup. Recommendation 3: mpMRI should be performed and interpreted in compliance with the current Prostate Imaging Reporting & Data System (PI-RADS) guidelines.

The Phoenix definition for biochemical failure (BCF) after radiotherapy uses nadir PSA (nPSA) + 2 ng/mL to classify a BCF and was derived from conventionally fractionated radiotherapy, which produces significantly higher nPSAs than stereotactic body radiotherapy (SBRT). We investigated whether an alternative nPSA-based threshold could be used to define post-SBRT BCFs.PSA kinetics data on 2038 patients from 9 institutions were retrospectively analyzed for low- and intermediate-risk PCa patients treated with SBRT without ADT. We evaluated the performance of various nPSA-based definitions. We also investigated the relationship of relative PSA decline (rPSA, PSAMedian follow-up was 71.9 months. BCF occurred in 6.9% of patients. Median nPSA was 0.16 ng/mL. False positivity of nPSA + 2 was 30.2%, compared to 40.9%, 57.8%, and 71.0% for nPSA + 1.5, nPSA + 1.0, and nPSA + 0.5, respectively. Among patients with BCF, the median lead time gained from an earlier nPSA + threshold definition over the Phoenix definition was minimal. Patients with BCF had significantly lower rates of early PSA decline (mean rPSA 1.19 vs. 0.39, p 0.0001) and were significantly more likely to reach nPSA + 2 ≥ 18 months (83.3% vs. 21.1%, p 0.0001). The proposed criterion (rPSA ≥ 2.6 or nPSA + 2 ≥ 18 months) had a sensitivity and specificity of 92.4% and 81.5%, respectively, for predicting BCF in patients meeting the Phoenix definition and decreased its false positivity to 6.4%.The Phoenix definition remains an excellent definition for BCF post-SBRT. Its high false positivity can be mitigated by applying additional criteria (rPSA ≥ 2.6 or time to nPSA + 2 ≥ 18 months).

Highlights • MRI and PSMA PET are complementary for delineating local recurrence after primary RT. • The union of CTVs on MRI and PSMA PET included, Purpose Our purpose was to evaluate intra-prostatic cancer volumes for salvage radiotherapy in men with recurrent prostate cancer confined to the prostate post-primary radiotherapy using mpMRI and 18F-DCFPyL PET/CT (PET). Methods Men with biochemical failure post-primary radiotherapy were enrolled in a multi-centre trial investigating mpMRI and PET. All men with isolated intra-prostatic recurrence are included in this secondary analysis. The intra-prostatic gross tumour volume (GTV) was manually delineated on mpMRI and was also delineated on PET using three methods: 1. manually, 2. using a 30% threshold of maximum intra-prostatic standard uptake value (SUVmax), and 3. using a 67% threshold of this SUVmax. Clinical target volumes (CTV) including expansions on each GTV were generated. Conformity indices were performed between the mpMRI CTV and each PET CTV. Correlation with biopsy and clinical outcomes were performed. Results Of the 36 men included, 30 (83%) had disease in two quadrants or less using the combination of mpMRI and PET. Mean target volume (union of CTV on mpMRI and CTV manually delineated on PET) was 12.2 cc (49% of prostate gland volume). 12/36 (33%) men had a biopsy. Per-patient sensitivity was 91% for mpMRI and 82% for PET. Conclusions mpMRI and PET provide complementary information for delineation of intra-prostatic recurrent disease. Union of CTV on mpMRI and PET is often less than 50% of the prostate, suggesting this imaging could help define a target for focal salvage therapy.

There has been growing utilisation of multiparametric magnetic resonance imaging (MPMRI) as a non-invasive tool to diagnose and localise clinically significant prostate cancer (CSPCa). This updated systematic review examines the use of MPMRI in patients with an elevated risk of CSPCa who have had a prior negative transrectal ultrasound systematic biopsy (TRUS-SB) and who were biopsy naive. MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews were searched for existing systematic reviews published up to September 2020. The literature search of the electronic databases combined disease-specific terms (prostate cancer, prostate carcinoma, etc.) and treatment-specific terms (magnetic resonance, etc.). Studies were included if they were randomised controlled trials (RCTs) comparing MPMRI to template transperineal mapping biopsy (TPMB) or to TRUS-SB. Thirty-six RCTs were eligible. For biopsy-naive men, accuracy of diagnosis of CSPCa showed sensitivities from 87 to 96% and specificities ranging from 29 to 45%. Meta-analyses for CSPCa showed increased detection favouring MPMRI-targeted biopsy over TRUS-SB by 3% (95% confidence interval 0-7%, P = 0.03) and decreased detection of clinically insignificant prostate cancer (CISPCa) favouring MPMRI by 8% (95% confidence interval -11 to 5%, P < 0.00001). Accuracy of MPMRI for men with prior negative biopsy showed sensitivities of 78-100% and specificities of 30-100%. Meta-analyses comparing MPMRI to TRUS-SB showed increased detection of 5% (95% confidence interval 3-7%, P < 0.0001) with a reduction of CISPCa detection of 7% (95% confidence interval 4-9%, P < 0.00001). The growing acceptance of MPMRI utilisation internationally and the recent publication of several RCTs regarding MPMRI in reducing CISPCa detection rates, particularly in biopsy-naive men, without loss of sensitivity for CSPCa necessitates the synthesis of updated evidence examining MPMRI in the diagnosis of CSPCa.

PURPOSE While brachytherapy is an effective treatment for localized prostate cancer, there has been a noticeable decline in its use. Training opportunity for prostate brachytherapy has been in steady decline, with some residents receiving little to no hands-on training. This work was developed to design a training environment that uses a phantom-based simulator to teach the process of TRUS-based prostate brachytherapy METHODS AND MATERIALS A prostate phantom was fabricated from a representative prostate patient TRUS scan. Three materials were used: gelatin powder, graphite powder, and water. The prostate was developed using 9% gelatin and 0.3% graphite per 100 ml water. Five radiation oncologists were asked to qualitatively score the phantom according to image quality, haptic feedback, needle insertion quality, and its compatibility with operative tools. The contrast-to-noise ratio (CNR) was estimated using different concentrations of graphite. The elasticity of the phantom was evaluated based on ultrasound elastography measurements RESULTS The prostate phantom had an average CNR of 3.94 ± 1.09 compared to real prostate images with a CNR of 2 ± 1.8. The average Young's modulus was computed to be 58.03 ± 6.24 kPa compared to real prostate tissue (58.8 ± 8.2 kPa). Oncologists ranked the phantom as “very good” for overall quality of the phantom. They reported that needle insertion quality was “very good” during a simulated brachytherapy procedure. CONCLUSION We have developed a 3D printing prostate phantom to be used for training purposes during prostate brachytherapy. The phantom has been evaluated for image quality and elasticity. The reconstructed phantom could be used as an anthropomorphic surrogate to train residents on prostate brachytherapy procedures.

Patients with localized prostate cancer comprise a large volume of treatments in radiation therapy centers. Occasionally, individual patient anatomy makes the safe delivery of an effective dose of radiation therapy challenging. We describe 2 cases of patients with a small bowel deep in the pelvis within the planning target volume with subsequent suboptimal radiation therapy treatment plans. We explore how we used the GU-Lok, a prostate immobilization device, to move the small bowel away from the prostate, and tighten target volume margins to help facilitate safe and effective treatment.

The ASCO/CCO guidelines recommend brachytherapy (BT) boost for eligible intermediate- (IR) or high-risk (HR) prostate cancer (PCa) patients. We present efficacy, toxicity and quality-of-life (QoL) outcomes in patients treated on a prospective protocol of MRI dose-painted high-dose-rate BT boost (HDR-BT) followed by 5-fraction pelvic radiotherapy (RT) and 6-18 months of androgen deprivation therapy (ADT).In this phase I/II study, IR or HR PCa patients received HDR-BT 15 Gy × 1 to prostate and up to 22.5 Gy to MRI nodule, followed by 25 Gy in 5, weekly fractions to pelvis. Toxicity was assessed using CTCAEv3.0, and QoL was captured using EPIC questionnaire. Biochemical failure (BF; nadir + 2.0), and proportion of patients with PSA 0.4 ng/ml at 4-years (4yPSARR) were evaluated. A minimally clinically important change (MCIC) was recorded if QoL score decreased0.5 standard deviation of baseline scores.Thirty-one patients (NCCN 3.2% favorable IR, 48.4% unfavorable IR and 48.4% HR) completed treatment with a median follow-up of 61 months. Median D90 to MR nodule was 19.0 Gy and median prostate V100% was 96.5%. The actuarial 5-year BF rate was 18.2%, and the 4yPSARR was 71%. One patient died of PCa. Acute grade 2 and 3 toxicities: GU: 50%, 7%, and GI: 3%, none, respectively. Late grade 2 and 3 toxicities were: GU: 23%, 3%, and GI: 7%, none, respectively. Proportion of patients with MCIC was 7.7% for urinary domain and 32.0% for bowel domain.This novel treatment protocol incorporating MRI dose-painted HDR-BT boost and 5-fraction pelvic RT with ADT is well tolerated.

Background and Purpose Long-term toxicity of high dose-rate brachytherapy as monotherapy for prostate cancer is not well defined. We report late toxicity and health related quality of life (HRQOL) changes from a randomized phase II clinical trial of two different fractionation schemes. Materials and Methods Eligible patients had NCCN low or intermediate risk prostate cancer. 170 patients were randomized to receive either a single 19 Gy or two-fractions of 13.5 Gy one week apart. Toxicity was measured using Common Terminology for Adverse Events (CTCAE) v4.0, and HRQOL was measured using the Expanded Prostate Index Composite (EPIC). Results Median follow-up was 63 months. The 5-year cumulative incidence of Grade 2 or higher genitourinary (GU) and gastrointestinal (GI) toxicity was 62% and 12% in the single-fraction arm, and 47% and 9% in the two-fraction arm, respectively. Grade 3 GU toxicity was only seen in the single fraction arm with a cumulative incidence of 2%. The 5-year prevalence of Grade 2 GU toxicity was 29% and 21%, in the single- and two-fraction arms, respectively, with Grade 2 GI toxicity of 1% and 2%. Beyond the first year, no significant differences in mean urinary HRQOL were seen compared to baseline in the two-fraction arm, in contrast to the single-fraction arm where a decline in urinary HRQOL was seen at 4 and 5 years. Sexual HRQOL was significantly reduced in both treatment arms at all timepoints, with no changes in the bowel domain. Conclusions HDR monotherapy is well tolerated with minimal impact on HRQOL.

This exploratory study evaluates immunological changes in high-risk Gleason 9 prostate cancer patients treated with EBRT+BT compared to EBRT alone. Notably, BT demonstrates the potential to elicit a T cell response which may support further investigation using circulating immune cells as predictive and prognostic biomarkers for radiotherapy response.

Stereotactic body radiotherapy (SBRT) is a technologically sophisticated form of radiotherapy that holds significant potential to effectively treat high-risk prostate cancer (HRPC). Prostate SBRT has been the subject of intense investigation in the context of low- and intermediate-risk disease, but less so for HRPC. However, emerging data are demonstrating its potential to safely and efficiently delivery curative doses of radiotherapy, both to the prostate and elective lymph nodes. SBRT theoretically hits harder through radiobiological dose escalation facilitated by ultra-hypofractionation (UHRT), faster with only five treatment fractions, and smarter by using targeted, focal dose escalation to maximally ablate the dominant intraprostatic lesion (while maximally protecting normal tissues). To achieve this, advanced imaging modalities like magnetic resonance imaging and prostate specific membrane antigen positron emmission tomography (PSMA-PET) are leveraged in combination with cutting-edge radiotherapy planning and delivery technology. In this focused narrative review, we discuss key evidence and upcoming clinical trials evaluating SBRT for HRPC with a focus on dose escalation, elective nodal irradiation, and focal boost.

Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT.PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0-2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1-2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258.We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI -1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference -1·3% [95% CI -3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe.In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited.Accuray.

Purpose Single-fraction HDR monotherapy for the treatment of localized prostate cancer is appealing, but published outcomes are discouraging. An approach to improve local control is MRI-guided focal dose-escalation to the dominant intraprostatic lesion (DIL). Here we report a comparison of outcomes from two phase II clinical trials with and without a focal boost. Methods Patients had low or intermediate-risk disease. Patients in Trial1 received a single 19 Gy HDR implant to the whole prostate. Trial2 incorporated an additional MRI-guided focal DIL boost to at least 23 Gy. ADT was not allowed. Toxicities (CTCAEv4.0) and quality of life (EPIC) were collected. Biochemical failure (BF) was defined as nadir +2. Univariate and multivariate logistic regression analysis was conducted to search for predictors of BF. Results Trial1 had 87 patients with a median follow-up of 62 months, while Trial2 had 60 patients with a median follow-up of 50 months. The five-year cumulative BF rate was 32.6% and 31.3%, respectively (p = 0.9). 77.5% of failures were biopsy-confirmed local failures, all of which underwent local salvage therapy. The addition of a DIL boost was not associated with worse toxicity or QOL. Baseline PSA and Gleason score correlated with BF, but none of the dosimetric parameters was a significant predictor of BF. Conclusions MRI-guided focal boost was safe and well tolerated, but did not improve local control after 19 Gy single-fraction HDR monotherapy, and the control rates were unacceptable. Single-fraction HDR monotherapy for prostate cancer should not be offered outside of clinical trials.

Active surveillance for prostate cancer relies on regular prostate specific antigen tests and surveillance biopsies. Compliance rates with biopsies vary but the subsequent impact on oncologic outcomes is not known. The objective of this study was to determine whether noncompliance with the confirmatory biopsy negatively impacts prostate cancer specific outcomes.A retrospective analysis was performed on a prospective single-arm cohort of men enrolled in active surveillance for prostate cancer between 1995 and 2018 with a median followup of 9.1 years. A total of 1,275 patients were enrolled and 1,043 had a minimum of 3 years of followup and were included in the analysis. Patients were stratified by compliance with a confirmatory biopsy within 24 months of enrollment in active surveillance. The primary outcome was recurrence-free survival. Secondary outcomes included metastatic-free survival and cause specific survival.A total of 1,275 patients were enrolled, and 1,043 had a minimum of 3 years of followup and were included in the analysis, of whom 425 were treated for localized prostate cancer. Patients noncompliant with the confirmatory biopsy had higher rates of recurrence after treatment (19% vs 12%, HR 1.64, 95% CI 1.19-2.26, p=0.003) and metastases (7% vs 2%, HR 3.56, 95% CI 1.8-7.0, p=0.0003) even after accounting for age, prostate specific antigen and Grade Group. Cause specific survival was not significantly different between the 2 groups. The results were consistent even in the subset of patients with Grade Group 1 disease at study entry.Noncompliance with a confirmatory biopsy compromises the control of prostate cancer in men followed on active surveillance. Patients and physicians should be aware of the importance of adhering to protocol for men on active surveillance.

Malignant spinal cord compression is one of the most dreaded complications of advanced malignancy, with patients presenting with progressive paralysis, paresthesia and/or autonomic dysfunction. The choice of management should be guided by the expected prognosis and outcome, not just from a neurological function point-of-view but also from the metastatic cancer itself. The main indications for surgery are: impending cord compression, spinal instability from tumour progression, bony retropulsion, for tissue diagnosis and for pain resistant to conventional therapies. Here, surgical principles, traditional and novel techniques and complications will be reviewed. For radiotherapy, multiple randomised studies have shown that for most patients a single fraction of external radiation has the same functional outcomes compared with multi-fractionation protocols. The experience of a specialised centralised interdisciplinary team will also be discussed.

Purpose To investigate the role of androgen deprivation therapy (ADT) in unfavorable intermediate risk (UIR) prostate cancer patients treated with high-dose rate (HDR) brachytherapy (BT) boost. Material and methods Data from 326 consecutive NCCN UIR prostate cancer patients treated in a single institution from 2009 to 2016 with 15 Gy HDR-BT boost plus 37.5 Gy external beam radiotherapy (EBRT) in 15 fractions to prostate and proximal seminal vesicles were retrospectively collected. Baseline information was collected and patients receiving vs. not receiving ADT were matched using a propensity-score model. Primary endpoint was biochemical-failure-free survival (BFFS). Kaplan–Meier estimates and stratified log-rank tests (adjusting for matched design) were used to compare BFFS, castration-resistance (CRFS) and metastasis free survival (MFS) outcomes between both groups. Results A total of 326 patients were included in the analysis of which 52 ADT patients were matched to 104 non-ADT patients in a 1:2 ratio. Median follow-up was 3.4 years and 5.5 years for ADT and non-ADT respectively. No significant baseline differences were observed. ADT was used for a median total time of 6 months (interquartile range [IQR]: 4–6) and delivered a median time of 2.7 months (IQR: 1.7–4.3) prior to HDR-BT. BFFS was significantly improved in the ADT group (stratified log-rank: p = 0.043) with 3-year and 6-year BFFS of 98% and 90% for the ADT group and 92% and 82% for the non-ADT group, respectively. No significant differences were detected for CRFS or MFS. Conclusion Short-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT.

Background Prostate stereotactic ablative radiotherapy (SABR) regimens differ in time, dose, and fractionation. We report an update of a multicentre, Canadian randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL), efficacy, and toxicity. Methods Men with intermediate risk prostate cancer were randomized to 40 Gy in 5 fractions delivered every other day (EOD) versus once per week (QW). Primary outcome was proportion of patients experiencing a minimally clinically important change (MCIC) in acute bowel QOL using EPIC. Secondary outcomes were toxicity, biochemical failure (BF), other QOL domains, and the rate of salvage therapy. Findings 152 men from 3 centers were randomized; the median follow-up was 62 months. Results are described for EOD versus QW. Acute bowel and urinary QOL was reported previously. Late changes in QOL were not significantly different between the two arms. There were 1 (1.3%) vs 3 (2.7%) late grade 3 + GI toxicities (p = 0.36) and 5 (6.7%) vs 2 (2.7%) late grade 3 GU toxicities (p = 0.44). Two and 5 patients had BF (5-year failure rate 3.0 vs 7.2%, p = 0.22); 0 and 4 patients received salvage therapy (p = 0.04). 5-Year OS and CSS was 95.8% and 98.6% with no difference between arms (p = 0.49, p = 0.15). 3 patients in the QW arm developed metastases. Interpretation Although we previously reported that weekly prostate SABR had better bowel and urinary QOL compared to EOD, the updated results show no difference in late toxicity, QOL, BF, or PSA kinetics. Patients should be counseled that QW SABR reduces short-term toxicity compared to QW SABR.

Purpose Dose-escalated stereotactic ablative radiotherapy (SABR) to the whole prostate may be associated with better outcomes but has a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on magnetic resonance imaging. We report the toxicity and quality-of-life (QOL) outcomes of 2 phase 2 trials of prostate and pelvic SABR, with or without a simultaneous DIL boost. Methods and Materials The first trial treated patients with high-risk prostate cancer to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk prostate cancer to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities, and QOL were assessed. Results Thirty patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 gastrointestinal or genitourinary toxicity between the 2 trials or in cumulative worst late gastrointestinal or genitourinary toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the 2 trials. Conclusions Prostate and pelvic SABR with a simultaneous DIL boost was feasible. Acute grade ≥2 toxicity, late toxicity, and QOL seemed to be comparable to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes, and randomized data are required to confirm these findings.

Purpose SABR offers an effective treatment option for clinically localized prostate cancer. Here we report the dosimetric predictors of late toxicity and quality of life (QOL) in a pooled cohort of patients from four phase II trials. Methods The combined cohort included all three prostate cancer risk groups. The prescription dose was 35–40 Gy in 5 fractions. Toxicity (CTCAE) and QOL (EPIC) were collected. Multiple dosimetric parameters for the bladder, rectum and penile bulb were collected. Univariate (UVA) followed by multivariate (MVA) logistic regression analysis was conducted to search for significant dosimetric predictors of late GI/GU toxicity, or minimal clinically important change in the relevant QOL domain. Results 258 patients were included with median follow up of 6.1 years. For QOL, bladder Dmax, V38, D1cc, D2cc, D5cc and rectal V35 were predictors of urinary and bowel MCIC on UVA. On MVA, only bladder V38 remained significant. For late toxicity, various parameters were significant on UVA but only rectal Dmax, V38 and bladder D2cc were significant predictors on MVA. Conclusions This report confirms that the high-dose regions in the bladder and rectum are more significant predictors of late toxicity and QOL after prostate SABR compared to low-dose regions. Caution must be taken to avoid high doses and hotspots in those organs.

External beam radiotherapy is a standard treatment option for localised prostate cancer and hypofractionation has become an alternative to conventionally fractionated radiotherapy. In patients who receive external beam radiotherapy, elective pelvic nodal irradiation is sometimes delivered, especially in patients with unfavourable disease who are at risk of micrometastatic spread of cancer into the regional nodes. One elegant approach to combine prostate hypofractionation with elective pelvic nodal irradiation is with a simultaneous integrated boost technique, where a radical hypofractionated dose is delivered to the prostate while the regional pelvic nodes receive a lower microscopic dose simultaneously in a single radiotherapy plan over the same number of treatment fractions. This article reviews the existing published literature evaluating such an approach.

Limited prospective data on focal salvage high-dose-rate (HDR) prostate brachytherapy is available. We sought to explore the toxicities, health-related quality of life (HRQoL), and efficacy of focal salvage HDR brachytherapy in a prospective clinical trial. This report presents the updated results of previously published data.Patients with locally recurrent prostate cancer after previous external beam radiation therapy and/or brachytherapy were enrolled. Patients received magnetic resonance imaging (MRI)-guided, ultrasound-based focal HDR brachytherapy delivered over 2 fractions of 13.5 Gy delivered 1 to 2 weeks apart. Androgen deprivation therapy (ADT) was not used.Thirty patients were treated between 2012 and 2019. At a median follow-up time of 39 months, the 3-year biochemical failure-free rate was 61.8% (95% confidence interval, 44.0%-86.6%), and the 3-year ADT/salvage therapy-free rate was 86.0% (95% confidence interval, 74.1%-99.8%). Seventeen patients experienced subsequent biochemical failure, 9 received ADT and/or further local salvage, and no patients died of prostate cancer. Of the 28 patients who had posttreatment MRI, 26 had a local treatment response. No acute grade ≥3 genitourinary/gastrointestinal toxicity was observed. One temporary late grade 3 genitourinary toxicity event occurred, but no late grade ≥3 gastrointestinal toxicity was seen. No significant decline in urinary or bowel HRQoL was observed.Focal salvage HDR brachytherapy has a favorable side effect profile, no significant decline in HRQoL, and the 3-year biochemical control rates are in line with those of other salvage options. Early MRI response at the treated site is common, but does not preclude subsequent biochemical failure.

INTRODUCTION: We aimed to determine the minimum cross-sectional ellipsoid area on magnetic resonance (MR) of intraprostatic nodules that best predicts for subsequent targeted biopsies revealing ≥ grade group (GG) 2 disease. METHODS: Forty-six patients previously diagnosed with GG 1 prostate adenocarcinoma who received cognitively fused, MR-guided, transperineal targeted biopsies in addition to six random biopsies were included in this analysis. A Youden cutpoint analysis was used to determine the ellipsoid area in the axial plane best predicting for ≥GG 2 disease within the targeted biopsy cores and logistic regression used to assess the result. RESULTS: Median time from MR imaging to targeted biopsy was 2.4 (1.4–5.5) months. Forty of 46 (87%) patients had one nodule and 6/46 (13%) had two separate nodules on MR that received targeted biopsy. Of the 52 nodules, five (10%), 33 (63%), and 14 (27%) were Prostate Imaging-Reporting and Data System (PI-RADS) 3, 4, and 5, respectively. Thirteen (25%), six (12%), and 33 (64%) were in the anterior, medial, and posterior regions of the prostate, respectively. Median area was 0.72 (0.49–1.29) cm(2) (average diameter 9.5 mm). Fifteen of 46 (33%) patients had ≥1 random biopsy and 20/52 (38%) nodules had ≥1 targeted biopsy revealing ≥GG 2 disease. The optimal area cutpoint was ≥0.7 cm(2), with an area under the curve of 0.671 (0.510–0.832). On logistic regression, area ≥0.7 cm(2) was solely predictive of targeted biopsy revealing ≥GG 2 disease (odds ratio 6.5, 1.3–32.4, p=0.022). CONCLUSIONS: Nodule area ≥0.7 cm(2) may predict for transperineal-based targeted biopsies being positive for ≥GG 2 disease when 1–2 cores are taken.

349 Background: Prostate stereotactic ablative radiotherapy (SABR) for localised prostate cancer is commonly delivered over 5 fractions. Focal boost to the dominant intraprostatic lesion (DIL) seen on multiparametric magnetic resonance imaging (mpMRI) is an approach for dose-escalation in prostate SABR. This is the first report of the outcomes of the 2SMART trial, a phase 2 single-arm study using 2-fraction prostate SABR with DIL boost. Methods: Men with low to intermediate risk prostate cancer were enrolled in the study. Three gold fiducial markers were inserted for image guidance. The clinical target volume (CTV) included the prostate gland, and the planning target volume (PTV) was a 2mm expansion antero-posterior and laterally, and 2.5mm supero-inferiorly. The DIL was contoured on fused mpMRI. The prescribed dose was 26Gy in 2 fractions (EQD2 110Gy, α/β of 1.4) to the CTV, and up to 32Gy in 2 fractions (EQD2 164Gy) to the DIL as long as the dose constraints for the organs at risks were not exceeded. Each fraction was delivered 1 week apart. Daily image guidance with cone-beam computed tomography was used pre- and post-treatment. The primary endpoint was acute (≤3 months) changes in quality of life (QOL), assessed using the EPIC questionnaire. Minimal clinically important change (MCIC) in QOL was defined as an EPIC score decrease of >0.5 standard deviation of the baseline EPIC score for each domain. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), and biochemical failure (based on Phoenix criteria). Results: 30 men were enrolled in the study, of which 2 (7%) had low risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range: 39-49 months). The median PSA nadir was 0.2ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. 1 (3%) and 17 (57%) had acute Grade 2 GU and GI toxicities, while 3 (10%) and 15 (50%) had late (>6 months) Grade 2 GU and GI toxicities. No acute or late Grade ≥3 GU or GI was reported. 10 (33%), 6 (20%), and 3 (10%) men had acute MCIC in urinary, bowel and sexual domains respectively. 15 (50%), 9 (30%) and 13 (43%) had late MCIC in urinary, bowel and sexual domain respectively. Conclusions: Two-fraction prostate SABR with DIL boost is a safe approach for dose-escalation for localised prostate cancer, with minimal impact on acute QOL, and no grade 3-4 toxicities. Clinical trial information: NCT03588819 .

Intermediate-risk prostate cancer is heterogenous. The absolute percentage of biopsied tissue positive for Gleason pattern 4 disease (APP4) is a possible prognostic measure. Here we sought to determine the impact of APP4 in a prospective multi-institutional pooled analysis of men with intermediate-risk prostate cancer treated with stereotactic body radiotherapy (SBRT).Patients with intermediate-risk prostate cancer treated with SBRT (40 Gy in five fractions or 26 Gy in two fractions) with or without androgen deprivation therapy treated on prospective clinical trials were included. Pathology reports were queried to obtain APP4, calculated as the percentage of Gleason pattern 4 disease within the tumour(s) multiplied by the percentage of total biopsied tissue positive for disease divided by 100. The optimal APP4 cut-off points for biochemical failure and distant metastasis were calculated and used as a stratification in the cumulative incidence of biochemical failure and distant metastasis. Multivariable competing risk models were developed.In tota, 227 patients were included. The median follow-up was 56.5 months. The optimal APP4 cut-off points were 5% for biochemical failure and 20% for distant metastasis. At 4 years, the cumulative incidence of biochemical failure was 23.6% and 2.3% for APP45% and ≤ 5%, respectively (P0.0001). The cumulative incidence of distant metastasis was 12.5% for APP420% and 1% for APP4 ≤ 20% (P = 0.02). APP4 sub-stratified favourable intermediate-risk prostate cancer and unfavourable intermediate-risk prostate cancer into groups at similarly low and similarly high risk of biochemical failure and distant metastasis. On multivariable competing risk analysis, APP45% (P = 0.0004) was significantly associated with biochemical failure, but APP4 (log) was not for distant metastasis (P = 0.08).APP4 may be an easily accessible promising prognostic measure for patients with intermediate-risk prostate cancer treated with SBRT. Incorporation of APP4 into prospective trials will help to determine its value.

Advances in imaging have changed prostate radiotherapy through improved biochemical control from focal boost and improved detection of recurrence. These advances are reviewed in the context of prostate stereotactic body radiation therapy (SBRT) and the ARGOS/CLIMBER trial protocol. ARGOS/CLIMBER will evaluate 1) the safety and feasibility of SBRT with focal boost guided by multiparametric MRI (mpMRI) and 18F-PSMA-1007 PET and 2) imaging and laboratory biomarkers for response to SBRT. To date, response to prostate SBRT is most commonly evaluated using the Phoenix Criteria for biochemical failure. The drawbacks of this approach include lack of lesion identification, a high false-positive rate, and delay in identifying treatment failure. Patients in ARGOS/CLIMBER will receive dynamic 18F-PSMA-1007 PET and mpMRI prior to SBRT for treatment planning and at 6 and 24 months after SBRT to assess response. Imaging findings will be correlated with prostate-specific antigen (PSA) and biopsy results, with the goal of early, non-invasive, and accurate identification of treatment failure.

INTRODUCTION: Identifying the optimal management of unfavorable-risk (Prostate Cancer Risk Stratification [ProCaRS] high intermediate-, high-, and very high-risk categories) non-metastatic prostate cancer is an important public health concern given the large burden of this disease. We compared the rate of metastatic progression-free survival among men diagnosed with unfavorable-risk non-metastatic prostate cancer who were initially treated with radiation therapy or radical prostatectomy. METHODS: Information was obtained from medical records at two academic centers in Canada from 333 men diagnosed with unfavorable-risk non-metastatic prostate cancer between 2007 and 2012. Median followup was 90.4 months. Men were eligible for the study if they received either primary radiation therapy (n=164) or radical prostatectomy (n=169), in addition to various adjuvant and salvage therapies when deemed clinically appropriate. Patients were matched on prognostic covariates using two matching techniques. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and confidence intervals (CI) for metastatic progression-free survival between groups. RESULTS: After matching, treatment groups were balanced on prognostic variables except for percent core positivity. Hazard ratios from all Cox proportional hazards models (i.e., before and after matching, and with and without multivariable adjustment) showed no difference in the rate of metastatic progression-free survival between groups (adjusted unmatched HR 1.16, 95% CI 0.63, 2.13, p=0.64). CONCLUSIONS: Metastatic progression-free survival did not differ between men diagnosed with unfavorable risk non-metastatic prostate cancer who were treated with either radiation therapy or radical prostatectomy.

Purpose: To evaluate the safety of stereotactic body radiation therapy (SBRT) for prostate cancer in men with inflammatory bowel disease (IBD). Methods and Materials: We queried a consortium database for patients with IBD receiving SBRT for prostate cancer between 2006 and 2012. Identified patients were matched with patients without a history of IBD in a 3:1 fashion based on dose, fractionation, use of androgen deprivation therapy, and age distribution. Logistic regression was used to evaluate the association between having IBD and experiencing acute and late gastrointestinal (GI) and genitourinary (GU) toxicities as scored on the Common Terminology Criteria for Adverse Events scale. Time to late toxicity was evaluated using proportional hazard Cox models. Our study was limited by absence of data on prostate size, baseline International Prostate Symptom Score, and rectal dose-volume histogram parameters. Results: Thirty-nine patients with flare-free IBD at time of treatment (median follow-up 83.9 months) and 117 matched controls (median follow-up 88.7 months) were identified. A diagnosis of IBD was associated with increased odds of developing any late grade GI toxicity (odds ratio [OR] 6.11, P

Summary Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10−7 and GAB2, p = 2.0 × 10−6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC., Genetic factors may distinguish who should receive active surveillance (AS) versus treatment following prostate cancer diagnosis. We undertook the first study to investigate this and report novel variants, genes, and risk scores associated with AS outcomes. These findings could help inform and individualize the decision of AS.

Purpose Stereotactic ablative radiotherapy (SABR) is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index and lead to a better quality of life (QOL). Here we report the outcomes of a QOL comparison between two phase II clinical trials: two vs. five fraction prostate SABR. Methods Patients had low or intermediate risk PCa. The doses prescribed were 26 Gy/2 and 40 Gy/5. Expanded prostate cancer index composite was collected. Urinary, bowel and sexual domains were analyzed. Minimal clinically important change (MCIC) was defined as >0.5 standard deviation. Results 30 and 152 patients were treated with 2-fraction and 5-fraction SABR. Median follow-up was 55 and 62 months. Five-year biochemical failure rate was 3.3% and 4.6%. The 2-fraction cohort had a significantly better mean QOL over time in the bowel domain ( p = 0.0004), without a significant difference in the urinary or sexual domains. The 2-fraction cohort had a significantly lower rate of bowel MCIC (17.8% vs 42.3%, p = 0.01), but there was no difference in urinary (24.1% vs 35.7%) or sexual (15.3% vs 29.2%) MCIC. For MCIC x2 (moderate QOL change), the 2-fraction trial had significantly lower MCIC rates in both the bowel (7.1% vs 24%, p = 0.04) and sexual (0 vs 17.6%, p = 0.01) domains. Conclusions 2-Fraction SABR is feasible to deliver and well tolerated, with significant signals of improved bowel and sexual QOL. A randomized trial of two vs. five fractions for prostate SABR is needed to confirm the promising findings of this study.

Purpose: To establish the safety and efficacy of gantry-mounted linear accelerator-based stereotactic body radiation therapy (SBRT) for low- and intermediate-risk prostate cancer. Methods: We pooled 921 patients enrolled on 7 single-institution prospective phase II trials of gantry-based SBRT from 2006 to 2017. The cumulative incidences of biochemical recurrence (defined by the Phoenix definition) and physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities (defined per the original trials using Common Terminology Criteria for Adverse Events) were estimated using a competing risk framework. Multivariable logistic regression was used to evaluate the relationship between late toxicity and prespecified covariates: biologically effective dose, every other day versus weekly fractionation, intrafractional motion monitoring, and acute toxicity. Results: Median follow-up was 3.1 years (range, 0.5-10.8 years). In addition, 505 (54.8%) patients had low-risk disease, 236 (25.6%) had favorable intermediate-risk disease, and 180 (19.5%) had unfavorable intermediate-risk disease. Intrafractional motion monitoring was performed in 78.0% of patients. The 3-year cumulative incidence of biochemical recurrence was 0.8% (95% confidence interval [CI], 0-1.7%), 2.2% (95% CI, 0-4.3%), and 5.1% (95% CI, 1.0-9.2%) for low-, favorable intermediate-, and unfavorable intermediate-risk disease. Acute grade ≥2 GU and GI toxicity occurred in 14.5% and 4.6% of patients, respectively. Three-year cumulative incidence estimates of late grade 2 GU and GI toxicity were 4.1% (95% CI, 2.6-5.5%) and 1.3% (95% CI, 0.5-2.1%), respectively, with late grade ≥3 GU and GI toxicity estimates of 0.7% (95% CI, 0.1-1.3%) and 0.4% (95% CI, 0-0.8%), respectively. The only identified significant predictors of late grade ≥2 toxicity were acute grade ≥2 toxicity (P < .001) and weekly fractionation (P < .01), although only 12.4% of patients were treated weekly. Conclusions: Gantry-based SBRT for prostate cancer is associated with a favorable safety and efficacy profile, despite variable intrafractional motion management techniques. These findings suggest that multiple treatment platforms can be used to safely deliver prostate SBRT.

To report the 5-year outcomes from a single institution, prospective, phase 1/2 study on hypofractionated, accelerated radiation therapy to the prostate bed after radical prostatectomy.Patients enrolled in this study were all eligible for postoperative radiation therapy and received a prescribed dose of 51 Gy in 17 fractions to the prostate bed. On follow-up, gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0; prostate-specific antigen (PSA) was evaluated and quality of life was assessed using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire.A total of 30 patients were enrolled between 2008 and 2011. Median age was 65 (52-75) years. Median pretreatment PSA was 0.12 ng/mL (0.01-1.42). Twenty-six (93%) patients had Gleason ≤7 disease, 13 (43%) had pT3 disease, and 20 (67%) had positive margins. Twenty-six patients (87%) underwent radiation therapy as salvage treatment. After a median follow-up of 6.4 (2.1-8.1) years, no patient experienced Common Terminology Criteria for Adverse Events grade 3/4 toxicity. Eleven patients (37%) had grade 2 genitourinary and 2 (7%) had grade 2 gastrointestinal toxicity. At baseline and 5 years after radiation therapy, mean EPIC urinary domain score was 80% (standard deviation, 18%) and 82% (17%). Mean EPIC bowel domain score was 93% (13%) and 93% (15%). One patient (4%) had a minimally clinically important change in urinary domain score and 1 patient (4%) had a minimally clinically important change in bowel domain score. Nelson-Aalen estimated cumulative incidence of biochemical failure was 31% (nadir +0.2) and 18% (nadir +2.0) at 5 years. Four-year PSA ≥0.4 was predictive of subsequent androgen deprivation therapy use (Nelson-Aalen cumulative incidence: 1.45; P .0001). Five patients (17%) received hormonal therapy for biochemical failure. Nelson-Aalen estimated cumulative incidence of hormone therapy use was 14% at 5 years. All patients who received hormone therapy had PSA0.4 at 4 years.In this phase 1/2 study, hypofractionated postoperative radiation therapy seems to have good clinical efficacy without significant late toxicity. Phase 3 studies are warranted.

To explore the changes in T2-weighted (T2w) and apparent diffusion coefficient (ADC) magnetic resonance imaging -derived radiomic features of the gross tumor volume (GTV) from focal salvage high-dose-rate prostate brachytherapy (HDRB) and to correlate with clinical parameters.Eligible patients included those with biopsy-confirmed local recurrence that correlated with MRI (T2w, ADC). Patients received 27 Gy in 2 fractions separated by 1 week to a quadrant consisting of the GTV. The MRI was repeated 1 year after HDRB. GTVs, planning target volumes, and normal prostate tissue control volumes were identified on the pre- and post-HDRB MRIs. Radiomic features from each GTV were extracted, and principle component analysis identified features with the highest variance.Pre- and post-HDRB MRIs were obtained from 14 trial patients. Principle component analysis showed that 18 and 17 features contributed to 93% and 86% of the variance observed in the T2w and ADC data, respectively. Sixteen T2w features and 1 ADC GTV feature were different from the control volumes in the pre-HDRB images (p0.05). Ten T2w and 7 ADC GTV post-HDRB features were different from those of pre-HDRB (p0.05).Exploratory analysis reveals several radiomic features in the T2w and ADC image GTVs that distinguish the GTV from healthy prostate tissue and change significantly after salvage HDRB.

Purpose Ultrahypofractionation is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index. Here we report the outcomes of a phase II prostate SABR trial using two fractions. Methods Patients had low or intermediate risk prostate cancer. Three gold fiducials were implanted for image guidance. The clinical target volume (CTV) included the prostate only, and the planning target volume (PTV) was a 3 mm expansion enabled through the use of a rectal immobilization device. The dose prescribed was 26 Gy in 2 weekly fractions (EQD2 110 Gy1.4). The primary endpoint was quality of life using EPIC, and minimal clinically important change (MCIC) was defined as an EPIC QOL decrease >0.5 SD. Results 30 patients were accrued with a median follow-up of 49.3 months. 10% had low-risk, 33% had favourable intermediate-risk and 57% had unfavourable intermediate-risk PCa. Five patients received a short course of ADT. Median nPSA was 0.2 ng/ml. One patient had BF and is being observed. 56.6% of patients had a 4yPSARR. Six (20.7%) patients had a MCIC in the urinary domain, 6 (21.4%) had a MCIC in the bowel domain, and 3 (20%) had a MCIC in the sexual domain. Conclusions Two-fraction SABR in prostate cancer is safe and feasible, with a minimal change in QOL and a low rate of late grade 3–4 toxicity. The PSA kinetics and biochemical control rates are encouraging given that the majority had unfavourable intermediate-risk disease, although longer follow-up is required.

Background and purpose To identify if, in intermediate risk prostate cancer (IR-PCa), the absolute percentage of biopsied tissue positive for pattern 4 disease (APP4) may be a predictor of outcome. Materials and methods 411 patients with IR-PCa were retrospectively reviewed. APP4 was calculated based on biopsy reports. Multivariable competing risk analysis was then performed on optimized APP4 cutpoints to predict for biochemical failure (BF), androgen deprivation use for BF (ADT-BF) and development of metastases (MD). Results Median follow-up for the cohort was 5.2 (Inter Quartile Range: 2.9–6.6) years. Median baseline PSA was 7.3 (5.3–9.8) ng/mL. 234 (56.9%) patients had T1 and 177 (43.1%) had T2 disease. Median APP4 was 2.00 (0.75–7.50)%. 38 (9.3%) patients experienced BF. The optimal cutpoint of APP4 for BF was >3.3% with an area under the curve (AUC) of 0.66. 17 (4.1%) received ADT-BF. The ADT-BF cutpoint was >6.6% with an AUC of 0.72. Eight (2.0%) developed MD. The MD cutpoint was >17.5% with an AUC of 0.86. Using APP4 >3.3 vs ≤ 3.3, log-transformed baseline PSA ln(PSA) (HR 2.5, 1.1–6.1; p = 0.037) and APP4 (HR 2.3, 1.1–4.7; p = 0.031) predicted for BF. Using APP4 >6.6 vs ≤ 6.6, ln(PSA) (HR 4.2, 1.4–12.4; p = 0.010) and APP4 (HR 3.7, 1.4–10.0; p = 0.009) were predictive of ADT-BF. APP4 >17.5 vs ≤ 17.5 alone was predictive of MD (HR 25.7, 4.9–135.3; p Conclusion APP4 cutpoints of >3.3%, >6.6% and >17.5% were strongly associated with increased risk of BF, ADT-BF and developing MD respectively. These findings may inform future practice when treating IR-PCa but require external validation.

Background Prostate cancer is an extremely heterogeneous disease. Despite being clinically similar, some tumours are more likely to recur after surgery compared to others. Distinguishing those that need adjuvant or salvage radiotherapy will improve patient outcomes. The goal of this study was to identify circulating microRNA that could independently predict prostate cancer patient risk stratification after radical prostatectomy. Methods Seventy-eight prostate cancer patients were recruited at the Odette Cancer Centre in Sunnybrook Health Sciences Centre. All patients had previously undergone radical prostatectomy. Blood samples were collected simultaneously for PSA testing and miRNA analysis using NanoString nCounter technology. Of the 78 samples, 75 had acceptable miRNA quantity and quality. Patients were stratified into high- and low-risk categories based on Gleason score, pathological T stage, surgical margin status, and diagnostic PSA: patients with Gleason ≥ 8; pT3a and positive margin; pT3b and any margin; or diagnostic PSA > 20 µg/mL were classified as high-risk (n = 44) and all other patients were classified as low-risk (n = 31). Results Using our patient dataset, we identified a four-miRNA signature (miR-17, miR-20a, miR-20b, miR-106a) that can distinguish high- and low-risk patients, in addition to their pathological tumour stage. High expression of these miRNAs is associated with shorter time to biochemical recurrence in the TCGA dataset. These miRNAs confer an aggressive phenotype upon overexpression in vitro. Conclusions This proof-of-principle report highlights the potential of circulating miRNAs to independently predict risk stratification of prostate cancer patients after radical prostatectomy. Electronic supplementary material The online version of this article (10.1186/s12967-019-1920-5) contains supplementary material, which is available to authorized users.