INTRODUCTION:Managing intermediate-risk prostate cancer is challenging due to the heterogeneity in patient outcomes within this risk category. Evaluating the absolute amount of Gleason pattern 4 disease (GP4) at biopsy using the total linear length of pattern 4 (GP4-TL) or absolute percentage of pattern 4 (APP4) may enhance risk stratification. This review aimed to determine if these absolute measures predict oncologic outcomes in IRPC and to identify optimal prognostic thresholds. METHODS:A systematic review was conducted following PRISMA guidelines. Studies included were those reporting the absolute amount of GP4 on biopsy and related outcomes in IRPC patients undergoing surgery or radiotherapy. Outcomes included biochemical recurrence, androgen deprivation therapy (ADT)-free survival, distant metastasis, prostate cancer-specific mortality, all-cause mortality, and adverse pathology. RESULTS:Seven studies with a total of 2523 patients were included. Analysis revealed that APP4 thresholds were highly predictive of biochemical recurrence, ADT-free survival, and distant metastasis. Both APP4 and GP4-TL were superior to relative % GP4 and Gleason grading (4+3 vs. 3+4) in predicting disease progression and mortality. CONCLUSIONS:The absolute amount of GP4 shows consistent associations with important clinical outcomes and offers an accessible and established method to enhance risk stratification. Further research is needed to define optimal thresholds to guide treatment decisions.

Purpose/Objective(s) Management of intermediate risk prostate cancer (IRPC) remains a challenge due to heterogeneity in outcomes within this risk category. A key aspect of risk stratification is the Gleason score. While the Gleason score in IRPC represents the relative proportion of pattern 3 vs pattern 4 (GP4) in biopsy specimens, it is not necessarily reflective of the volume of GP4 disease. Calculating the total amount of GP4 at biopsy may improve risk stratification as GP4 is thought to be the driver of cancer spread. The aim of this study is to investigate measures of absolute amount of GP4 at biopsy to determine if they are predictive of oncologic outcomes including biochemical recurrence, distant metastasis, and mortality in IRPC. Materials/Methods A systematic review in accordance with PRISMA guidelines was performed. Embase, MEDLINE, and CENTRAL were searched from inception to May 2023. Studies which quantified absolute amount of GP4 on biopsy in IRPC (Gleason 3+4 or 4+3) patients who subsequently underwent surgery or radiotherapy were included. Measures of GP4 amount, biopsy strategy, biochemical recurrence (BCR), adverse pathology, and survival outcomes were collected. A narrative summary of results was performed. Results Of the 2038 records reviewed, 7 retrospective studies with 2523 patients were identified for inclusion. Four studies reported on Total Linear Length of Pattern 4 across all biopsy cores (GP4TL), two evaluated the Absolute Percentage of Pattern 4 (APP4) at biopsy (% prostate cancer tissue x % pattern 4 x 100), and one investigated both. Biopsy strategy was reported for 1573 patients, of which 1100 (69.9%) were systematic, 436 (27.7%) were targeted, and 37 (2.3%) were both. Optimal APP4 cut-points of 3.3-5%, 6.6%, and 17.5-20% in 2 studies were highly predictive of BCR, androgen deprivation therapy-free survival, and distant metastasis at 4-years post-radiotherapy, respectively. Multivariable analyses yielded significant associations between GP4TL/APP4 and BCR, adverse pathology, and survival outcomes after adjusting for age, clinical stage, PSA, % positive cores, and BED. APP4 and GP4TL outperformed other GP4 quantifications (i.e. relative %GP4, Gleason 3+4 vs 4+3, number of cores involved) in predicting distant progression, prostate cancer-specific mortality, all-cause mortality, and adverse pathology. One study analyzed outcomes by biopsy strategy but found no significant heterogeneity. Conclusion While no major risk stratification system incorporates absolute amount of GP4 measures, it appears to better risk stratify men with IRPC. Given that this can be calculated prior to therapy initiation and is prognostic for long-term outcomes, future studies may be able to determine if treatment intensification (i.e. with hormone therapy) or deintensification (i.e. active surveillance) may be based on APP4 or GP4TL. Future research would also benefit from consistent reporting of biopsy strategy, as GP4TL and APP4 may be increased by use of targeted biopsies.

Purpose/Objective(s) Stereotactic ablative body radiotherapy (SABR) is an emerging treatment for patients with primary renal cell carcinoma (RCC), however variation in treatment protocols can exist between institutions. The goals of this study were to measure the variation in contouring RCC tumors for patients being treated with SABR and to develop consensus recommendations. Materials/Methods An international panel of 16 radiation oncologists was created from the IROCK meeting during ASTRO 2023. Four patient cases were: Case 1, a renal tumor greater than 10 cm in size with an IVC tumor thrombus; Case 2, a central renal tumor abutting the renal hilum; Case 3, a local recurrence of RCC post-nephrectomy; and Case 4, a residual tumor post-radiofrequency ablation (RFA). For each Case, panelists were asked for radiation planning details and to contour the target volumes on representative axial images using a computer-based training tool. Comparison of panelist contours with the were performed using the Dice-Similarity Coefficient (DSC), the Mean Distance to Agreement (MDA) and the Hausdorff Distance (HD). The DSC measures the overlap between two contours, so a higher DSC suggests greater agreement. The MDA and HD represent the mean and maximum distances between points on the two contours, so higher MDA and HD represent lower agreement. Consensus target volumes were derived using the STAPLE algorithm and discussed amongst the panel. Results Altogether, the panel included radiation oncologists from Canada, the USA, Australia, the Netherlands, and India. All panelists had previously treated at least 10 patients with SABR for primary RCC. Table 1 shows the DSC, MDA and HD for each case. Using an ANOVA analysis, for all Cases, the DSC, MDA and HD were not statistically different between participants (p = 0.32, p = 0.24, and p = 0.23, respectively). On qualitative inspection of participant contours, Case 4 showed the most agreement, followed by Case 3, Case 2, and then Case 1. Conclusion There was good agreement from our international expert panel on contouring renal tumors in all four Cases, with Case 4 having the greatest agreement, and Case 1 having the least agreement. Consensus recommendations based on this study may help improve the quality of SABR for RCC moving forward.

PURPOSE:This phase 1 study aimed to assess the safety and feasibility of SABR therapy delivery to all sites of polymetastatic disease (>10 metastases). METHODS AND MATERIALS:A 3 + 3 study design was used with 5 dose levels from 6 Gy (6 Gy × 1) to 30 Gy (6 Gy weekly × 5). Dose-limiting toxicity (DLT) was defined as any grade 4 or 5 toxicity or more than 3 grade 3 toxicities within 6 weeks of treatment. The primary endpoint was the maximal tolerated dose, defined as the dose level where ≥2/6 of patients experienced DLT. Secondary endpoints included quality of life (Functional Assessment of Cancer Therapy - General and European Quality of Life 5 Dimension 5 Level) at 6 weeks posttreatment, progression-free survival, and overall survival. RESULTS:Thirteen patients were accrued: 12 Gy (n = 3), 18 Gy (n = 3), 24 Gy (n = 4), and 30 Gy (n = 3), and 207 lesions were treated. Nine patients (69%) had acute toxicity: grade 1 (n = 6, 46%), grade 2 (n = 2, 15%; n = 1 pneumonitis and n = 1 fatigue), and grade 3 (n = 1, 7.7% neutropenia). There were no grade 4 or 5 toxicities. Mean ± SD quality of life (Functional Assessment of Cancer Therapy - General and European Quality of Life 5 Dimension 5 Level health state) was 80.4 ± 21.9 and 77.4 ± 20.9 at baseline versus 76.4 ± 21.8 and 68.0 ± 24.2 at 6-week follow-up, respectively (p = .009 and p = .055, respectively). With a median follow-up of 8.7 months posttreatment (IQR, 2.4-24 months), 8 of 13 patients had disease progression (62%). The median and 12-month progression-free survival were 3.6 months and 11.3%, respectively. The median and 12-month overall survival were 13.8 months and 62%, respectively. CONCLUSIONS:In this phase 1 trial, SABR therapy for polymetastatic disease was technically feasible with acceptable acute toxicity at dose levels up to 30 Gy (6 Gy weekly × 5). DLT was not observed.

HDR monotherapy with 27 Gy delivered in 2 fractions in treatment of prostate cancer is well tolerated with high rates of disease control and minimal toxicity. Dose summation between 2 fractions of HDR brachytherapy is feasible, with rectal dose predicting acute GI toxicity. The lack of association between dose metrics and urinary toxicity raises the potential for further dose escalation.

Background and Purpose: Local recurrences after previous radiotherapy (RT) are increasingly being iden-tified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT.Materials and Methods: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient-and cancer -specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of >= 75% was set, with a majority opinion being >= 50%.Results: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and system-atic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion pre-ferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. Conclusion: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.(c) 2023 Elsevier B.V. All rights reserved. Radiotherapy and Oncology xxx (2023) xxx-xxx

Purpose: 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. Methods and Materials: 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. Results: 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. Conclusions: 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. (c) 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Following adoption of moderately hypofractionated radiotherapy as a standard for localised prostate cancer, ultrahypofractioned radiotherapy delivered in five to seven fractions is rapidly being embraced by clinical practice and international guidelines. However, the question remains: how low can we go? Can radiotherapy for prostate cancer be delivered in fewer than five fractions? The current review summarises the evidence that radiotherapy for localised prostate cancer can be safely and effectively delivered in fewer than five fractions using high dose rate brachytherapy or stereotactic body radiotherapy. We also discuss important lessons learned from the single-fraction high dose rate brachytherapy experience.

PurposeLocal recurrences after previous radiotherapy (RT) are increasingly being identified with increasing use of molecular imaging in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option for radiorecurrent prostate cancer. While supported by multiple prospective studies, limited comparative data exists to guide optimal patient selection and treatment technique. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT.Materials and MethodsInternational experts in salvage prostate BT were invited (n=34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up after salvage. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being set at ≥ 50%.ResultsThirty international experts agreed to participate, and the response rates were 100% (30/30), 93.3% (28/30) and 100% (30/30) for the first, second and third rounds of the survey respectively. Consensus was achieved for 56% (18 of 32) statements. Consensus was achieved in several areas of patient selection, including: 1) A minimum of 2-3 years from initial RT and consideration of salvage BT; 2) MRI and PSMA PET should be acquired prior to salvage; 3) Both a targeted and systematic prostate biopsy should be performed; 4) Salvage BT can be considered after any initial RT technique; and 5) Any Gleason Score at recurrence could be considered for salvage. Several areas did not reach consensus and were controversial: 1) Cut off for maximum T stage and PSA at time of salvage; 2) Whether ADT should be used with salvage BT (and duration); 3) Whether it was appropriate to combine local salvage with SBRT for oligometastatic disease and 4) Whether salvage BT may be repeated more than once. More than 50% of respondents preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland salvage could be appropriate depending on the clinical situation. There was no single preferred dose fractionation for salvage prostate BT.ConclusionsThese findings will inform development of an international expert consensus statement for salvage prostate BT. Consensus was achieved on 56% of statements, though several controversial areas were identified. While our results highlight there is no single preferred approach for salvage BT, areas of controversy will be relevant for the design of future prospective studies and clinical trials of salvage BT.

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.

e17052 Background: Men with localized prostate cancer have many options for initial definitive treatment. In 2015, Cancer Care Ontario Quality Based Procedures (QBP) recommended that men undergoing radical prostatectomy (RP) in Ontario be seen by a radiation oncologist (RO) or discussed at a multidisciplinary case conference (MCC) prior to surgery. An a-priori target rate of 76% was set by QBP, but to our knowledge, has not been reported upon to date. Our objective was to use population-based data to explore factors associated with not receiving RO consult/MCC prior to RP. Methods: Men with localized prostate cancer diagnosed and treated in Ontario, Canada with RP between 2007 and 2017 were identified using administrative data from the Institute for Clinical Evaluative Sciences. Physician billing data was utilized to identify patients who received RO consult/MCC prior to RP. Trends were evaluated using the Cochran-Armitage test. Multivariable logistic regression was used to identify patient and provider factors predictive of RO/MCC prior to RP. Results: 31,467 men with localized prostate cancer underwent RP between 2007 and 2017. Prior to RP, 29.3% of men were seen by RO, 1.0% underwent MCC, and 1.6% had both. RO consult/MCC prior to RP increased from 18.0% in 2007 to 47.8% in 2017 ( p<0.001). On multivariable analysis, the Odds Ratio (OR) of RO consult/MCC prior to RP between the lowest and highest geographic regions (LHINs) was 8.79 (95% CI 6.83–11.32, p<0.001). RO consult/MCC was less likely to occur for patients living further from the nearest cancer center (OR 0.74 per 50km, 95% CI 0.70–0.77, p<0.001) and more likely to occur for men residing in the highest versus lowest income quintile regions (OR 1.42, 95% CI 1.30–1.55, p<0.001). Men with NCCN Low (OR 1.31, 95% CI 1.16–1.47, p<0.001), High (OR 1.20, 95% CI 1.09–1.31, p<0.001) or Very High (OR 1.24, 95% CI 1.11–1.30, p<0.001) risk disease were more likely to receive RO consult/MCC compared to those with favourable-intermediate risk disease. Of the 128 urologists who performed at least 10 RP between 2016 and 2017, RO referral/MCC rate ranged from 0% to 100%, with 31 urologists (24.2%) having ≥76% of their patients seen prior to RP. To meet QBP targets in 2017, an additional 701 men would have needed RO consult/MCC. If all were seen by RO, approximately 2.4 additional full time equivalent RO positions would be needed. Conclusions: Despite increasing rates of utilization, a large proportion of men are not seen by RO or MCC prior to RP in Ontario, Canada. While the largest factors predicting RO consult/MCC discussion appear to be geographic and which urologist performs the RP, these factors are closely intertwined. In addition, these factors may be related to RO availability and radiation system capacity, which would need to be addressed to meet patient demand should QBP consultation rates be mandated to reduce disparities in pre-RP consultation practices.

We found substantial variability in many OAR dose constraints used in ongoing clinical trials evaluating SABR in oligometastatic disease. Future research and recommendations for standardized OAR dose constraints, as well as consistency in implementing PRV margins, should be a priority for the field of radiation oncology.