365 Background: Salvage radiotherapy (RT) is an effective curative salvage of relapse after radical prostatectomy (RP). CAPRA S score predicts for relapse after salvage RT. The DADSPORT meta-analysis suggests those with low CAPRA S score do not benefit from benefit of androgen ablation (AA) to salvage RT. A rising PSA during salvage RT may be important in predicting which patients may benefit from treatment intensification such as addition of AA to salvage RT. Herein we report on outcomes of salvage RT without AA in relation to rising PSA during RT. Methods: 32 patients were treated with salvage RT alone without AA (either because of low risk or patient preference) for rising PSA rising post RP. All patients had a PSA prior to and at least twice during RT at least 3 weeks apart. Patients were treated with 66 Gy in 33# to prostate bed. Patients were followed for PSA q 6 months post RT. Those with a PSA rising to over 0.2 were considered to have relapsed. Actuarial outcomes for relapse were assessed with multivariate analysis including CAPRA S score (low, intermediate, and high), and by 6 year progression free survival estimate from MSKCC nomogram (dichotomized around the median). Results: Median and IQR of PSA at time of salvage RT were 0.24 (0.2-0.55). 19% of patients had rising PSA during RT. 19 patients (60%) also received 46 Gy in 23# to pelvic nodes in phase 1 of RT. 34% of patients had PSMA PET prior to RT (none showing involved nodes or metastases). CAPRA S scores were low (15%), intermediate (69%), and high (15%). Relapse rates did not differ by CAPRA S score, although numbers were small. Three-year freedom from relapse rates were 16% for those with rising, and 49% without rising PSA during RT respectively (p=0.006). Three-year freedom from relapse rates were 9% for those below the median MSKCC nomogram risk, and 68% for those above the median respectively (p<0.001). Only rising PSA during RT was significant on MVA. Three patients had a rising PSA and a negative PSMA prior to salvage RT: all three relapsed within 1 year of RT. Of eight patients who had a falling PSA during RT and a negative PSMA PET prior to salvage RT: only 1 relapsed within 3 years of salvage RT. Conclusions: A rising PSA during salvage RT without AA is prognostic for relapse, and may be particularly relevant in the PSMA PET era. This may be a factor to considered when deciding whether to intensify therapy during salvage RT, either by adding adjuvant ADT, and/or using a PSMA PET to guide dose escalation.

Although many patients with muscle-invasive bladder cancer (MIBC) achieve a pathologic complete response (CR) following neoadjuvant therapy (NAT), subsequent definitive bladder treatment (DBT) - radical cystectomy (RC) or trimodal therapy (TMT) remain standard treatments. Preliminary evidence suggests that a subset of patients may avoid DBT, but a definitive randomized comparison has not been conducted. NeoBLAST aims to evaluate the feasibility of randomizing patients with MIBC who achieve a clinical CR (cCR) following NAT to active surveillance (AS) versus DBT and to ultimately demonstrate the non-inferiority of AS. This study is an open-label phase 2/3 randomized controlled trial. Patients with resectable MIBC cT2-T4aN0M0 who achieve a cCR after receiving NAT are randomized 1:1 to AS or DBT. cCR determined by conventional imaging, circulating tumor DNA, bladder MRI, and template bladder biopsy. NeoBLAST phase 2 opened in August 2025 with the plan to enrol for 2 years and expand to a multicenter phase 3 trial in 2027. The phase 2 primary endpoint is feasibility to randomize, defined as ≥25% (≥18 of 72) acceptance of randomization in patients with cCR. The phase 3 primary endpoint is metastasis-free survival at 2 years. To determine a non-inferiority margin of 10%, the trial will need to randomize 172 patients with cCR. This study has the potential to be practice-changing by establishing the non-inferiority of AS in a randomized setting, but carries a risk of poor feasibility and unintended cross over after randomization. FUNDING: Canadian Institutes of Health Research and the Vancouver Prostate Centre. ETHICS AND TRIAL REGISTRATION: University of British Columbia H23-02447, NCT06537154.

306 Background: Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) trial randomized patients to prostate brachytherapy (PB) or the External beam RT (EBRT) boost (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the EBRT arm received an additional 32 Gy in 16 fractions, and those in the PB arm received a 115 Gy 125I implant. The trial previously demonstrated a large difference in biochemical relapse favoring brachytherapy (PB) boost. At present, the median follow-up from start of treatment of all patients is 15 (IQR 10.7, 17.8) years. Herein we report the 15-year actuarial survival events. Methods: Two hundred patients with a median age of 68 (IQR 62,73) were randomized to EBRT and 198 to PB. Active study follow-up stopped at 10 years. Cause of death was determined on chart review and study report forms during active study follow-up, and was augmented with death registry data, and medical records audits thereafter. Fifteen-year overall survival and cumulative risk of death from prostate cancer were estimated using Cox and Fine and Gray analysis respectively with multivariable analysis (MVA) significant variables on univariate including - randomization, clinical T stage, log of initial PSA, Gleason grade group (1-3 vs 4-5), percent positive cores, and age at treatment. A sensitivity analysis included unknown cause of death as prostate death. Results: 213 patients (54%) have died: 64 (16%) of prostate cancer, 48 (12%) of other cancer, 35 (9%) of cardiovascular disease, 49 (12%) of other known causes, and 17 (4%) of unknown cause of death. The age of patients alive at last censoring was 82 (IQR 77,88). Overall survival at 15 years was 55.0% (95% CI 48.4 – 62.4) and 60.9% (95% CI 54.4 – 68.1) for EBRT and PB arms respectively, (HR 1.02, 95%CI 0.78 – 1.33, p = 0.908 on MVA). The cumulative incidence of prostate death at 15 years was 8.6% (95%CI 5.2 – 13.0) for PB and 16.4% (95%CI 11.6 – 22.0) for EBRT (p=0.007). In a sensitivity analysis where cases of unknown cause of death were counted as prostate deaths, the cumulative incidence of prostate death at 15 years was 14.3% (95%CI 9.8 – 19.5) for PB and 19.4% (95%CI 14.2 – 25.3) for EBRT (p=0.067). Conclusions: At 15 years, there is no definite evidence of an overall survival benefit with PB boost in ASCENDE-RT and the trend to a prostate cancer specific survival advantage with PB is limited by ascertainment of cause of death. Thus, although prostate cancer was the single most common cause of mortality in ASCENDE-RT, our results suggest that even large improvements in b-NED, such as those demonstrated with PB in ASCENDE-RT, are unlikely to improve 15-year overall survival by more than 10% for a population whose median age, performance status, and prognostic variables are similar to ASCENDE-RT participants. Clinical trial information: NCT00175396 .

BACKGROUND AND PURPOSE:SABR-5 was a provincially coordinated, single-arm phase II trial of SABR for patients with up to five extracranial metastases across all six BC Cancer centres. The primary objective was to prospectively quantify treatment-related toxicity in a population-based setting. This analysis reports extended follow-up and long-term toxicity outcomes. MATERIALS AND METHODS:Adults with oligometastatic or oligoprogressive disease (≤5 extracranial metastases) were enrolled between 2016 and 2020, when SABR for these indications in BC was available only through this trial. All grade ≥ 3 events underwent central review by a provincial toxicity committee. Toxicity was evaluated using crude per-patient rates, cumulative incidence methods, annual landmark analyses to year 5, and assessment of toxicity duration. Median follow-up for this update was 54.2 months. RESULTS:A total of 380 patients were treated (median age 69 years; 32% female). Most patients (91%) had one or two lesions treated. Crude per-patient rates of treatment-related toxicity were 18.9% for grade 2, 5.8% for grade 3, 0.0% for grade 4, and 0.3% for grade 5. There were no additional treatment-related deaths beyond the single previously reported case. The most frequent grade ≥ 3 toxicities were fracture (2.9%) and pain (1.8%). The cumulative incidence of grade 2 and grade ≥ 3 toxicity at 5 years was 24% and 7%, respectively. Annual landmark analyses demonstrated that most evaluable patients remained grade 0-1 at each timepoint. Analysis of toxicity duration demonstrated that most grade 3 events resolved within a year (median durations typically < 12 months), and persistent long-term toxicity was uncommon and predominantly low-grade. CONCLUSION:SABR delivered within a population-based, quality-assured program is associated with a low incidence of late high-grade toxicity and no new treatment-related deaths. These findings provide durable reassurance regarding the long-term safety of SABR for patients with limited extracranial metastatic disease. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02933242.

Importance Patients with prostate cancer have a high burden of cardiovascular risk factors, often suboptimally controlled, and adverse cardiovascular outcomes. Objective To determine whether the routine referral of patients with prostate cancer to a cardiovascular specialist to implement a systematic risk factor strategy is more likely to reduce adverse cardiovascular outcomes and improve risk factor control than usual care. Design, Settings, and Participants This randomized clinical trial included patients with prostate cancer from 55 sites in 8 countries between 2015 and 2025. Eligible patients were diagnosed with prostate cancer during the past 12 months; had received treatment with androgen deprivation therapy (ADT) for the first time within the past 6 months; or planned to start ADT in the next month. Patients taking a statin with a systolic blood pressure of 130 mm Hg or lower were ineligible. Data were analyzed from May 25 to August 7, 2026. Intervention Patients were allocated in a 1:1 ratio to receive usual care alone or usual care plus routine referral to an internist or cardiologist. The specialists provided a systematic intervention, including a target of systolic blood pressure of 130 mm Hg or lower and a statin medication, irrespective of the patient’s cholesterol levels (even if not usual or guideline-driven practice); encourage smoking cessation; and provide guidance on diet and exercise. Main Outcomes and Measures Hierarchical composite of cardiovascular death, myocardial infarction, stroke, heart failure, suboptimal cholesterol (total cholesterol, >155 mg/dL [to convert to mmol/L, multiply by 0.0259]) and suboptimal blood pressure (systolic blood pressure, >130 mm Hg) as evaluated by the win ratio. Results The analysis included 2487 patients with prostate cancer (mean [SD] age, 68 [8] years). During median (IQR) follow-up of 5.8 (2.7-8.2) years, the win ratio in favor of the intervention was 1.60 (95% CI, 1.42-1.81), mostly attributable to lower cholesterol in the intervention group (mean difference, 12 mg/dL; 95% CI, 9-15 mg/dL) as a consequence of greater protocol-mandated statin use. Mean (SD) close-out systolic blood pressure values were 131.1 (16.9) mm Hg in the intervention group and 132.9 (18.3) mm Hg in the control group. There was no difference in time to cardiovascular death, myocardial infarction, stroke, or heart failure between groups (subdistribution hazard ratio, 1.08; 95% CI, 0.79-1.49). Conclusions and Relevance In this randomized clinical trial, routine referral of patients with prostate cancer to a cardiovascular specialist lead to improved outcomes, specifically through better cholesterol control. However, it is uncertain whether this reduced clinical cardiovascular events. Trial Registration ClinicalTrials.gov Identifier: NCT03127631

PURPOSE:The use of SABR for oligometastatic cancer is expanding, but prospective long-term survival data are limited. This study reports long-term secondary outcomes of overall survival (OS), progression-free survival (PFS), local control, and prognostic factors from the population-based phase 2 SABR-5 trial. METHODS AND MATERIALS:The SABR-5 trial was a single-arm phase 2 study with the primary endpoint of toxicity, conducted across 6 regional cancer centers in British Columbia, Canada. Eligible patients had ≤5 oligometastases (new or uncontrolled by prior therapy, including induced oligometastatic disease), were ≥18 years of age with ECOG performance status 0-2, and had a life expectancy ≥6 months. All lesions were treated with SABR. RESULTS:From November 2016 to July 2020, 380 patients were treated. The most common histologies were prostate (32.1%), colorectal (16.6%), and breast (11.1%). Most patients (90.5%) had 1-2 lesions. Median follow-up was 54.2 months. Median OS was 64.6 months (95% CI, 61.0-68.1) and median PFS was 14.6 months (95% CI, 11.6-17.6). Five-year OS, PFS, and local control were 58.6% (95% CI, 53.5-63.7), 20.3% (95% CI, 16.2-24.4), and 85.1% (95% CI, 82.0-88.1), respectively. On multivariable analysis, worse OS was independently associated with ECOG ≥1, larger tumor diameter, colorectal or lung histology, 1-2 lesions, no upfront systemic therapy, and absence of synchronous oligometastatic disease. Predictors of worse PFS included ECOG ≥1, larger tumor diameter, no upfront systemic therapy, oligoprogression, and metachronous disease. CONCLUSIONS:In this large population-based cohort consisting of genuine oligometastatic, oligoprogressive, and induced oligometastatic disease, the median OS and PFS were 64.6 months and 14.6 months, respectively. The favorable OS and PFS may suggest a role for SABR beyond the genuine oligometastatic paradigm, highlighting the potential benefit of durable local tumor control in this patient population.

PURPOSE/OBJECTIVES:There are limited data on outcomes in patients with ultracentral pulmonary oligometastases treated with SABR. The purpose of this study was to determine whether ultracentral location was prognostic for toxicity and survival. MATERIAL AND METHODS:Oligometastatic lung lesions treated on the single-arm phase 2 SABR-5 trial were retrospectively stratified into 2 cohorts: ultracentral tumors (UC), defined as planning target volume overlap or direct tumor abutment to the proximal bronchial tree, esophagus, great vessels, or heart, and nonultracentral tumors. Cohorts were compared with respect to grade ≥ 2 toxicity, progression-free survival (PFS), and overall survival (OS). RESULTS:In total, 41 patients with 45 ultracentral metastases and 93 patients with 172 nonultracentral metastases underwent SABR. The most common primary histologies were colorectal (30%), lung (13%), and renal (13%), and these did not differ between groups. Patients with UC had a lower median PFS of 5.8 months compared with 15.8 months in patients with non ultracentral tumors (P < .001). OS was also worse in the UC cohort: median 29.0 months versus not yet reached (P < .001). On multivariable regression, UC remained prognostic for worse PFS (hazard ratio 2.18, P = .004) and OS (hazard ratio 3.45, P < .001). Groups had similar rates of local tumor control. Patients with UC had higher 2-year cumulative incidence of polymetastatic progression: 69.2% versus 31.4% (P < .001). The 2-year cumulative incidence of grade ≥ 2 toxicity was 14.6% for patients with UC and 9.8% for patients with nonultracentral tumors (P = .74). There were no grade 4 or 5 toxicities. CONCLUSIONS:In this prospective patient cohort, SABR for ultracentral tumor had low toxicity rates and good local control. However, ultracentral location was an adverse prognostic feature for survival. This finding should be validated with larger studies and may be a factor when weighing the benefit versus risk of SABR in patients with pulmonary oligometastases.

BACKGROUND:Distant progression is the predominant failure pattern after metastasis-directed stereotactic body radiotherapy (SBRT) for oligometastatic disease, but prognostic tools to guide post-progression management are lacking. We aimed to validate the prognostic value of distant metastasis velocity (DMV) for overall survival (OS) and widespread failure-free survival (WFFS) after distant progression. METHODS:Two independent international cohorts of patients with extracranial oligometastatic disease (≤5 lesions) who developed distant progression after SBRT were analyzed. The primary outcome was OS; secondary outcome was WFFS in the subgroup of patients with repeat oligometastasis at distant progression. DMV was defined as the number of new or progressing metastases per month after initial metastasis-directed SBRT. RESULTS:Among 563 patients (median age 68 years, 56 % male), DMV stratified prognosis in both cohorts. In the prospective cohort (n = 221), median OS was 35.7 months for patients with DMV ≤ 0.5 metastases/month versus 20.6 months for DMV > 0.5 (P = 0.0001). In the retrospective cohort (n = 342), OS was 32.8 vs. 12.1 months (P < 0.0001). Similar trends were observed for WFFS (prospective cohort, n = 91: 6.8 vs. 3.0 months, p = 0.42; retrospective cohort, n = 341: 18.8 vs. 6.1 months, p < 0.0001). CONCLUSION:Higher DMV was consistently associated with worse outcomes after progression in oligometastatic disease. Its reproducibility across tumor types and independent cohorts supports DMV as a simple, dynamic, and clinically relevant prognostic marker. DMV should be further explored as a component of multimodal prognostic models to refine patient selection and guide post-progression treatment strategies.

22 Background: Metastases directed therapy (MDT) in metachronous hormone sensitive prostate cancer (mHSPS) patients has been shown to delay systemic therapy and to a lesser extent improve oncological outcome. To date there has not been strong data to suggest benefit of MDT in castration resistant prostate cancer (CRPC). In this multi-centric randomized phase II trial, we sought to determine the benefit of stereotactic body radiotherapy (SBRT) in oligometastatic CRPC (omCRPC) patients. Methods: PCS-9 was originally designed as an adaptive randomized phase II/III trial conducted across 13 sites in Canada. Given that ARPIs became the standard of care in mHSPC, the study was stopped at the phase II level after 100 mCRPC patients, with 5 or less metastatic sites, were recruited. Patients were randomly assigned in a 1:1 ratio to androgen deprivation therapy (ADT) + enzalutamide (Enza), arm-1 or ADT + Enza + SBRT to the conventionally (CT/MRI/bone scan) identified oligometastatic sites, arm-2. The primary endpoint was radiological progression free survival (rPFS), defined as radiological progression or death from any cause. Results: Of the 100 omCRPC patients, 48 were randomized to ADT+Enza and 52 to ADT+Enza+SBRT. There was no difference in patient or disease characteristics. One to three metastases occurred in 89.6% of arm-1 and 84.6% of arm-2, while visceral involvement accounted for 2.1 and 5.8%, respectively. The addition of SBRT doubled the median rPFS compared to ADT and Enza alone. rPFS was 4.6 years in the SBRT group and 2.3 years in the ADT and Enza arm, a 50% risk reduction (HR: 0.5 with 95% CI, 0.28-0.88; p=0.017). Similarly, biochemical progression free survival (bPFS) was 4.5 years for the SBRT arm and 2.6 years for ADT and Enza alone arm, a 44% risk reduction (HR:0.56 95% CI, 0.31-0.99 p=0.0425). At the time of this analysis there was a 27% risk reduction of death with the addition of SBRT (HR:0.73; 95% CI, 0.33-1.64; p=0.463), however the median OS had not been reached for either arm. Time to subsequent therapy was significantly delayed by the addition of SBRT. The median time to subsequent therapy was 5.1 years for the SBRT arm vs. 3.8 years for the ADT + Enza alone arm, a risk reduction of 48% (HR:0.52; 95% CI, 0.27-0.047; p:0.047). There was no difference in adverse event between the arms including fatigue, hypertension and fracture. Only 4 patients in the SBRT arm reported transient pain flare at the SBRT site and one patient had acute asymptomatic pneumonitis. Conclusions: The addition of SBRT to oligometastatic sites in mCRPC significantly improved rPFS, improved bPFS and delayed the time to next line of therapy. Although OS remains immature, there was numerical reduction in the risk of death. These results strongly suggest that SBRT to oligometastatic sites is beneficial and should be considered in patients with oligo-metastatic CRPC. Clinical trial information: NCT02685397 .

PURPOSE:To compare local failure, marginal failure, and toxicity in non-spine bone metastases (NSBMs) treated with versus without a CTV for stereotactic ablative radiotherapy (SABR). METHODS:The study included all patients in British Columbia treated with SABR for NSBMs on the SABR-5 trial (November 2016 - July 2020) and on the BC Oligometastases Registry (August 2020- October 2022). NSBMs were stratified based on CTV use for treatment planning. RESULTS:148 patients with 183 NSBMs were included. 145 (79 %) NSBMs were treated with a CTV. Most lesions received 35 Gy in 5 fractions (80 %) or 24 Gy in 2 fractions (15 %). Local failure rates did not differ, with a 2-year local failure of 8.6 % (95 % confidence interval [CI] 3.9-13.2) with a CTV and 8.1 % (95 % CI 0-16.8) without a CTV (p = 0.53). Marginal failure did not differ (6.4 % [95 % CI 2.3-10.5] and 2.6 %, [95 % CI 0-7.7], respectively [p = 0.23]). 2-year cumulative incidence of grade ≥ 2 toxicity did not differ (15.8 %, 95 % CI 9.7-21.9 and 16.2 %, 95 % CI 4.2-28.2 respectively; p = 1.00). On multivariable regression, use of a CTV was not associated with the risk of local-marginal failure (hazard ratio [HR] 1.81, 95 % CI 0.62-5.31, p = 0.28). Extraosseous extension (HR 2.59, 95 % CI 1.2-5.7, p = 0.02) and lack of receipt of systemic therapy (HR 0.27, 95 % CI 0.1-0.5, p = 0.0002) were associated with higher risk. CONCLUSIONS:Use of a CTV was not associated with local or marginal failure or toxicity. Extraosseous extension and lack of receipt of systemic therapy were associated with higher risk of local-marginal failure.

BACKGROUND:The role of metastasis-directed therapy (MDT) in castration-resistant prostate cancer (CRPC) remains unclear. Prostate Cancer Study 9 (PCS-9) aimed to evaluate the benefits of stereotactic body radiotherapy (SBRT) in addition to standard systemic therapy in patients with oligometastatic CRPC. METHODS:This open-label, randomised, phase 2 trial was conducted across 13 Canadian academic and community oncology centres. Male patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0-2, and histologically confirmed oligometastatic CRPC (≤5 metastases), who had progressed on androgen deprivation therapy (ADT), were randomly assigned (1:1) to ADT-enzalutamide (ENZA; 160 mg once daily) or ADT-ENZA-SBRT to all oligometastatic sites. Randomisation was completed by sequentially numbered, sealed opaque envelopes, and stratified by the location of the metastasis. The primary endpoint was radiographic progression-free survival. Analysis was performed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT02685397, and was halted and completed at the phase 2 stage. FINDINGS:Between Oct 18, 2016, and July 31, 2023, 102 male patients were randomly assigned to ADT-ENZA (n=49) or ADT-ENZA-SBRT (n=53); after excluding one patient per treatment group due to early withdrawal and insufficient data, 48 patients in the ADT-ENZA group and 52 patients in the ADT-ENZA-SBRT group were included in the final analysis. Most patients were White (80 [80%]) and median age was 73·0 years (IQR 67·0-79·5). At a median follow-up of 4·8 years (IQR 3·4-5·0), ADT-ENZA-SBRT significantly improved radiographic progression-free survival compared with ADT-ENZA alone (median radiographic progression-free survival, 4·6 years [95% CI 3·7-not reached] vs 2·3 years [1·4-3·7]; hazard ratio 0·48 [95% CI 0·27-0·86]; p=0·014). The most common grade 3 treatment related adverse event was impotence (eight [57%] of 14 patients in the ADT-ENZA group and nine [75%] of 12 patients in the ADT-ENZA-SBRT group). There were no grade 4 toxicities and no treatment-related deaths. INTERPRETATION:These results demonstrate that SBRT, when combined with ADT-ENZA, prolongs disease control in oligometastatic CRPC by doubling median radiographic progression-free survival, with similar toxicity profiles between the groups. These findings support integrating SBRT into the treatment paradigm for oligometastatic CRPC. FUNDING:Jewish General Hospital (Astellas Canada).

To characterize radiotherapy (RT) use for brain metastases (BM) in British Columbia (BC) from January 2017 to December 2022. Patients who received BM-directed RT were identified from the BC Cancer registry and RT delivery software. Patient demographics, disease characteristics, and RT details were collected for three periods: 2017–2018 (P1), 2019–2020 (P2), and 2021–2022 (P3). Chi-square and Kruskal-Wallis tests analyzed clinical factors associated with RT use. Kaplan-Meier overall survival was assessed. Among 2,797 patients, 3,317 RT courses were delivered. The most common primaries were non-small cell lung cancer (NSCLC) (49%), small cell lung cancer (SCLC) (18%), breast (9%), and gastrointestinal (7%). The proportion of BM RT per year decreased for SCLC but increased for breast, gastrointestinal, melanoma, gynecologic, and sarcoma cancers. RT courses delivered increased across periods (755, 1,217, and 1,345, respectively), with an increasing proportion of patients receiving ≥2 RT courses (10%, 13%, 16%, p=0.05). The most common dose was 20Gy in 5 fractions. Whole-brain RT (WBRT) declined (75%, 61%, 49% from P1 to P3), while focal RT, particularly stereotactic RT (SRT), increased from 148 courses (P1) to 416 (P3). Median survival from diagnosis was 14 months, and from first BM RT was 5 months. One-year OS from diagnosis improved (42%, 56%, 63%, p<0.01), but OS from first BM RT remained stable (30%, 32%, 33%, p=0.12). BM RT use in BC has increased, shifting from WBRT to focal RT, particularly SRT. While OS from diagnosis has improved, survival after BM RT remained stable.

Purpose Although stereotactic ablative radiation therapy (SABR) is known for low toxicity and safety, its combined use with specific systemic therapies requires further investigation. This study aims to evaluate the toxicity of SABR in combination with various systemic therapies. Materials and Methods A secondary analysis of the SABR-5 trial evaluated grade 2+ and 3+ toxicities post-SABR in patients who had received high-risk or non-high-risk systemic therapies before SABR at 4 predefined intervals: concurrent with SABR, 1 day to 1 week prior, 1 to 2 weeks prior, or 2 to 12 weeks prior. High-risk systemic therapy was a priori defined as drugs that may increase treatment toxicity when delivered in close proximity to SABR. This category encompasses cytotoxic chemotherapy, multitargeted tyrosine kinase inhibitors, CDK 4/6 inhibitors, EGFR inhibitors, anti-VEGF agents, and anti-CTLA-4 agents. Results Among 380 patients, grade 2+ toxicity rates were 17.3% (35/202) off systemic therapy, 19.2% (19/99) on non-high-risk therapy, and 42.9% (3/7) on high-risk therapy concurrent with SABR. Grade 3+ rates were 3.5% (7/202), 4.0% (4/99), and 28.6% (2/7), respectively. On multivariable analysis, concurrent use of high-risk systemic therapy was associated with a higher risk of grade 3+ toxic effects (OR, 14.88; P = .009). No significant risk was noted when high-risk drugs were used within 1 week, 2 weeks, or 2 to 12 weeks of SABR or with any non-high-risk drugs. Grade 2+ toxic effects associated with concurrent high-risk systemic therapy were primarily bone/pain related. Increased tumor diameter also elevated grade 2+ toxicity risk (per 1 cm increment; G2+ OR, 1.19; P < .001). Conclusion Concurrent use of high-risk drugs has demonstrated a potential of increased SABR-related toxicity, warranting caution in their concurrent use with SABR. In contrast, combining non-high-risk drugs (eg, hormonal therapy) with SABR did not increase risk. Further research is essential to identify risks associated with this therapeutic combination.

Lay Summary This study evaluated radiotherapy utilization for brain metastases in British Columbia from 2017–2022. Overall, 2,793 patients received 3,313 radiotherapy courses. The use of radiotherapy increased by 124% over the study period. The use of focal radiotherapy, particularly conformal stereotactic radiotherapy, increased substantially, while use of whole-brain radiotherapy declined. Given the lower cognitive impact of focal approaches, these findings reflect evolving treatment practices and have important implications for future resource planning, workforce needs, and access to increasingly complex radiation technologies as the number of patients with brain metastases continues to grow.

BackgroundProstate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is becoming standard of care for men with biochemical recurrence (BCR) of prostate cancer. The implications of a negative PSMA PET/CT scan in this population remain unclear. This study aims to assess the outcome of patients with BCR post radical prostatectomy (RP) who have negative [18F]DCFPyL PET/CT scan at relapse.MethodsThis is a post-hoc subgroup analysis of a prospective non randomized clinical trial. One hundred and one patients (median age, 75 years) with BCR after RP, who tested negative on [18F]DCFPyL PET/CT and subsequently either underwent salvage radiotherapy (sRT) with or without androgen deprivation therapy (ADT) or were followed without active treatment, were included. Freedom from progression (FFP) after negative PSMA PET/CT was determined based on follow-up imaging selected as per clinical practice. Uni- and multivariate Cox regression analyses were performed to examine the association of patients' characteristics, tumor-specific variables, and treatment with clinical progression at the last follow-up. FFP at 1-, 2-, and 3-year were reported using Kaplan Meier analysis.ResultsThe median PSA level at PET/CT was 0.56 ng/mL (range, 0.4-11.3). Sixty five (64%) patients were followed without receiving further treatment, and 36 (36%) received sRT (18% to the prostate bed only and 18% to the prostate bed and pelvic lymph nodes) within 3 months of the PSMA PET. Seventeen of the sRT patients (17 of 36, 47%) received concomitant androgen deprivation therapy (ADT). Median follow-up was 39 months. Subsequent clinical progression was detected in 21 patients (21%), with 52% in pelvic lymph nodes, 52% in the prostatic fossa, 19% in distant lymph nodes, 14% in lungs, and 10% in bones. The FFP was 95% (95% CI: 91%-99%) at 12 months, 87% (95% CI: 81%-94%) at 24 months, and 79% (95% CI: 71%-88%) at 36 months. Multivariate Cox regression analysis revealed that an initial International Society of Urological Pathology (ISUP) grade 5 was significantly associated with clinical progression at the last follow-up (hazard ratio, 5.1, P value, 0.04). Furthermore, the receipt of sRT correlated significantly with lower clinical progression at the last follow-up (hazard ratio, 0.2, P value, 0.03), whereas other clinical and tumor-specific parameters did not. Following surveillance-only and sRT, 29% (19 of 65) and 6% (2 of 36) of patients, respectively, showed clinical progression. In the sRT group, no significant difference was observed in FFP between patients who underwent sRT to the prostatic fossa versus those who received sRT to the prostatic fossa and pelvic lymph nodes, although the numbers in these groups were small.ConclusionsThis study suggests that salvage radiotherapy is associated with a decreased or delayed clinical progression in patients with biochemical recurrence following radical prostatectomy who have negative PSMA PET/CT scan results. The analysis also underscores the prognostic significance of the initial ISUP grade, with ISUP grade 5 being associated with worse outcomes.Trial registrationRegistered September 14, 2016; NCT02899312.