Citations

e13890 Background: Many oncology practices have reported continued use of telemedicine since onset of the COVID-19 pandemic. However, the future sustainability of telemedicine within oncology practices remains unclear, particularly because federal policies that enabled adoption in response to the public health emergency (PHE) have not been made permanent. Understanding similarities and differences in telemedicine utilization at high-volume oncology centers is crucial for shaping evidence-based policy that enables equitable access to oncology care across varying geographies. Methods: This is a cross-sectional, year-over-year, retrospective cohort analysis of trends in telemedicine utilization across all medical oncology clinical appointments conducted among adult patients (age >18) from January 2019 to December 2023 at Stanford Medicine Cancer Center (SM) – comprising multiple campuses in the California Bay Area – and the Mayo Clinic Comprehensive Cancer Center (MC) – a multiregional cancer practice with tertiary referral campuses in Minnesota, Florida, and Arizona, as well as community-based clinics throughout the Upper Midwest. Results: Both institutions exhibited a similar trend in telemedicine adoption over time. This was characterized by an initial surge in utilization following the PHE declaration in March 2020, followed by sustained utilization rates from 2021 to 2023. However, telemedicine use as a proportion of the overall practice differed significantly between institutions. At SM, the rate of telemedicine visits as a proportion of overall clinical practice was 60.3% (49,136/ 81,502) in 2021, 59.9% (52,247/ 87,215) in 2022, and 57.2% (55,007/ 96,163) in 2023. At MC, the proportion of telemedicine utilization was 12.8% in 2021 (23,873/186,086), 14.7% in 2022 (28,985/196,777), and 14.0% in 2023 (30,208/215,941). Deployment in the setting of new versus return visits also differed between institutions. In 2023, telemedicine accounted for 53.7% (6,440/11,998) of new and 57.7% (48,567/84,165) of return visits at SM, compared to 15.5% (3,359/21,728) and 13.8% (26,849/194,213) at MC. Additionally, while video visits were the predominant modality used to conduct telemedicine visits at both institutions from 2021 onward, in 2023 phone visits still made up 17.9% (5,394/30,208) of all telemedicine visits at MC, compared to just 5.4% (2,990/55,007) at SM. Conclusions: Stanford Medicine and Mayo Clinic exhibited a pattern of initial growth of telemedicine adoption in 2020, followed by sustained utilization from 2021-2023. We observed unique differences in the overall proportion, visit type deployment, and modality of telemedicine utilization between institutions. However, this study confirms telemedicine visits have remained a fixture of medical oncology care for many patients at these institutions since the COVID-19 pandemic.

e12562 Background: Previous research has suggested that breast cancer (BC) diagnosed during pregnancy or the postpartum period exhibits more aggressive clinical features, possibly due to pregnancy-related hormonal changes, immune modulation, and alterations in the mammary microenvironment compared to nulligravid or women many years out from pregnancy. Emerging data have demonstrated potential worse outcomes for patients (pts) diagnosed in post-partum. This study evaluated the influence of timing of diagnosis in relation to pregnancy history and recency of childbirth on long-term outcomes in a modern cohort of young pts with early-stage BC. Methods: Pts with stage I–III BC age < 40y in the prospective Young Women’s Breast Cancer Study (YWBCS) were categorized at diagnosis as Nulligravid (no prior pregnancy), Nulliparous (prior pregnancy without live birth), Currently Pregnant, or Parous (subdivided by time since last childbirth: within 5 years [≤ 5y PP], and 5–10 years postpartum [5–10y PP]). Baseline characteristics and outcomes were compared across BC subtypes (estrogen receptor+/HER2- [ER+/HER2-], HER2+, and triple-negative BC [TNBC]). Prognostic analyses for distant recurrence-free survival (DRFS) used Cox models. Results: 859 pts were included, 257 (30%) nulligravid, 50 (6%) nulliparous, 37 (4%) pregnant, and 515 (60%) parous (348 [68%] were ≤5y PP, and 167 [32%] were 5–10y PP). Median follow-up was 133 (6–209) months. Median age at diagnosis was lower in nulligravid pts (33 vs. 35–38 years); T1 tumors were most common in pts >5y PP (62%), and N0 status was highest in nulligravid pts (64%) (all p < 0.0001). Pregnant pts had higher rates of TNBC (27%), and T3 tumors (14%), N1 status, N1 (41%), and Grade 3 (81%) tumors compared to other groups (all p < 0.0001). Overall, only tumor size (T2-T4 vs T1, HR 2.03; 95% CI 1.37–3.03) and nodal status (N1 vs N0, HR 2.22; 1.48–3.34; N2/3 vs N0, HR 3.23; 1.96-5.33) were independently associated with worse DRFS; pregnancy history was not: nulligravid + nulliparous pts had no significant differences in DRFS compared to Pregnant (HR 1.46; 0.75–2.86), Parous <5y PP (HR 0.86; 0.58–1.26), and Parous 5–10y PP (HR 0.89; 0.54–1.48). Subgroup analyses by BC subtype (Table) and sensitivity analyses (excluding currently pregnant pts or separating nulligravid and nulliparous pts) demonstrated no significant associations between pregnancy history and DRFS. Conclusions: In this cohort study of very young patients with early breast cancer with contemporary treatment including management of breast cancer during pregnancy, pregnancy history and recency of pregnancy were not independent predictors of long-term disease outcomes. DRFS results by subgroup. Pregnancy Group N (%) HR (95% CI) ER+/HER2- Nulligravid + Nulliparous 173 (38.1) Ref Pregnant 16 (3.5) 0.93 (0.32–2.70) Parous ≤5y PP 177 (39.0) 0.77 (0.45–1.29) Parous 5–10y PP 88 (19.4) 0.78 (0.39–1.53) HER2+ Nulligravid + Nulliparous 77 (30.8) Ref Pregnant 11 (4.4) 3.27 (0.80–13.38) Parous ≤5y PP 113 (45.2) 1.50 (0.60–3.75) Parous 5–10y PP 49 (19.6) 1.45 (0.45–4.66) TNBC Nulligravid + Nulliparous 56 (36.8) Ref Pregnant 10 (6.6) 1.92 (0.61–6.09) Parous ≤5y PP 57 (37.5) 0.68 (0.28–1.63) Parous 5–10y PP 29 (19.1) 1.16 (0.43–3.14)

5064 Background: FoundationOneCDx (F1CDx) supports two FDA-approved biomarkers to guide treatment decisions for ICI for patients with mCRPC: MSI status and TMB. MSI-H and TMB-H (10+ mut/MB) have strongly overlapping prevalence. We sought to better characterize ICI outcome associations of TMB-H / non-MSI-H population and relative effectiveness of taxanes & ICI among patients who received these agents in sequence. Methods: Following a prespecified analysis plan, this study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine mCRPC clinico-genomic database (FH-FMI CGDB), with data originating from ~280 US cancer clinics (~800 sites of care). Inclusion criteria included patients with mCRPC treated with single-agent anti-PD(L)1 therapy in the FH network between 1/1/2011 - 3/30/2024. This study used the MSI and TMB algorithms from the tissue based F1CDx. Time to next treatment (TTNT) and OS were assessed with Kaplan-Meier plots and in multivariable Cox models adjusted for ECOG performance score, socioeconomic status, prior treatment history, and baseline PSA. Among patients who received taxanes in a prior line of therapy, the effectiveness (TTNT1 vs. TTNT2) of taxane and ICI were compared. Results: Among 2995 prostate cancer tissue specimens in the database, 95 (3.1%) were MSI-H and 142 (4.7%) were TMB-H. 94 (3.1%) were MSI-H & TMB-H, 1 was MSI-H & TMB-L, and 48 (1.6%) were TMB-H & not MSI-H. Among these, 84 patients with mCRPC were treated with ICI and met inclusion criteria, including MSI-H & TMB-H (n = 30), non-MSI-H & TMB-H (n = 8), and non-MSI-H and TMB-L (n = 46). The respective median TTNT on ICI was 8.0 vs. 9.6 vs. 3 months. The respective median OS from initiation of ICI was 10.9 vs. not reached vs. 4.4 months. In multivariable models evaluating ICI only, compared to non-MSI-H & TMB-L, the MSI-H & TMB-H group had more favorable TTNT (HR: 0.20, 95%CI: 0.10 – 0.41, p < 0.001) and OS (HR: 0.33, 95%CI: 0.16 – 0.70, p = 0.004), and the non-MSI-H & TMB-H group also had more favorable TTNT (HR: 0.13, 95%CI: 0.04 – 0.45, p = 0.002) and OS (HR: 0.20, 95%CI: 0.05 – 0.75, p = 0.017). 50 of the 84 (60%) patients treated with ICI had prior mCRPC taxane treatment. Better TTNT2 on subsequent ICI vs. prior taxane was observed for MSI-H (HR: 0.49, 95%CI: 0.23 – 1.01, p = 0.051) and TMB-H (0.54, 95%CI: 0.30 – 0.98, p = 0.044), but the opposite was true for non-MSI-H and TMB-L subgroups, with significant treatment interactions for each (p = 0.0018, p = 0.00052). Conclusions: TMB-H (4.7%) is more prevalent than MSI-H (3.1%) by F1CDx in mCRPC. Non-MSI-H / TMB-H (1.6%) in the routine practice cohort have similar outcome associations on ICI to MSI-H. Both MSI-H and TMB-H by F1CDx are predictive of differential benefit for ICI vs. taxanes in later mCRPC treatment lines.

5060 Background: Rucaparib significantly improved radiographic progression-free survival (rPFS) in men with BRCA-mutated chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) vs a control arm of physician’s choice of therapy (docetaxel or androgen-receptor pathway inhibitor [ARPI] therapy: abiraterone acetate or enzalutamide) in the randomized, multicenter, open-label, phase 3 TRITON3 (NCT02975934) study. Herein, we conducted an analysis to determine the impact of germline vs somatic mutation status on the efficacy of rucaparib. Methods: Patients were randomized 2:1 to receive rucaparib 600 mg BID or physician’s choice of docetaxel or ARPI following progression while on 1 prior second-generation ARPI in any setting. The primary endpoint was rPFS. Color Health did genetic testing. Treatment-emergent adverse events (TEAEs) were reported for the BRCA subgroup. Results: In the rucaparib arm, 201/270 patients had BRCA mutations, and in the physician’s choice arm, 101/135 patients had BRCA mutations. Of patients with BRCA mutations: in the rucaparib arm, 80/201 (40%) were germline and 116/201 (58%) were somatic with 5/201 (2%) BRCA mutation status unknown, while in the physician’s choice arm, 39/101 (39%) were germline and 48/101 (48%) were somatic with 14/101 (14%) BRCA mutation status unknown. rPFS was significantly improved with rucaparib treatment vs physician’s choice in both the germline and somatic mutation groups (germline: HR, 0.52 [95% CI, 0.32–0.84]; somatic: HR, 0.38 [95% CI, 0.25–0.59]). Incidence rates of TEAEs were similar overall between patients with germline and somatic BRCA mutations in both arms. Conclusions: Rucaparib improves progression-free survival for patients with mCRPC with either germline or somatic BRCA mutations with a manageable safety profile. These data support the use of rucaparib as a beneficial treatment option for patients with BRCA-mutated mCRPC with germline or somatic mutations. Clinical trial information: NCT02975934 .

5048 Background: Ra-223, an alpha-emitting radionuclide, is the first agent of its kind approved for the treatment of mCRPC. Although a pivotal phase 3 study evaluated its short-term safety, there is a need to investigate its long-term safety. The REASSURE study prospectively examined the long-term safety of Ra-223, including secondary primary malignancies (SPMs), in a large patient (pt) population enrolled across Europe, the United States, Israel, and Latin America. Methods: We report final analyses (data cut-off Oct 24, 2024) of REASSURE (NCT02141438), a global, noninterventional study (enrolment 2014–2017). Primary outcomes were the incidence of SPMs, short- (30 days) and long-term (7 years) safety events, and bone marrow suppression (BMS) management in pts who had ≥1 Ra-223 dose. Secondary outcomes included overall survival (OS). Results: Analyses included 1472 pts; median follow-up was 17 months (range 0.3–95.4). Median age was 73 years and 80% of pts had an ECOG PS of 0/1. In evaluable pts, median alkaline phosphatase, prostate-specific antigen, and lactate dehydrogenase levels were 133 U/L, 59 ng/mL, and 266 U/L, respectively. Overall, 81% of pts had bone-only metastases at baseline; 19% of pts had metastases in the bone plus other sites (mostly lymph nodes). Prior treatments included abiraterone (48% of pts), enzalutamide (39%), docetaxel (39%), and cabazitaxel (9%). Pts received a median of 6 Ra-223 doses; 67% received ≥5 doses. SPMs occurred in 2% of pts (25 SPMs in 24 pts). Of these pts, 16 (67%) and 1 (4%) had received prior or concomitant radiotherapy, respectively. Overall, 3% of pts had drug-related serious adverse events >30 days after completing Ra-223. Fractures were reported in 10% of pts and were less common in pts with (7% of 605) than without (12% of 867) concomitant BHA use. During Ra-223 and up to 30 days after the last dose, there was no notable difference in the incidence of abnormal platelet counts between pts with (3%) or without (2%) prior chemotherapy; similar findings were seen for abnormal neutrophil counts (5% and 5%, respectively). BMS treatments, assessed from the start of Ra-223, were more common in pts who had received prior taxanes (38%) than in those who had not (26%). The most common life-prolonging therapies received after Ra-223 were docetaxel (18%), enzalutamide (15%), abiraterone (11%), and cabazitaxel (11%). Median OS was 15.6 months (95% CI, 14.6, 16.4); pt subgroups that survived the longest will be characterized and presented. Conclusions: This real-world safety analysis of pts with mCRPC is the longest follow-up of a radiopharmaceutical reported to date and supports the well-established favorable safety profile of Ra-223. The incidence of SPMs was low. The rate of fracture was low, especially in the presence of BHAs. Prior taxane chemotherapy use had no impact on hematological toxicity. Clinical trial information: NCT02141438 .

504 Background: Axillary surgery in breast cancer is used for staging and therapeutic purposes, but axillary lymph node dissection (ALND) confers high risk of complications including lymphedema. Accordingly, trials have focused on right-sizing axillary surgery, with options ranging from complete omission of surgery, sentinel lymph node (SLN) surgery, targeted axillary dissection (TAD), or ALND. Identifying a biomarker to reliably predict nodal burden would facilitate accurate selection of surgical management. We evaluated whether the presence or absence of ctDNA in the blood pre and post NAC is associated with residual nodal burden. Methods: I-SPY2 is a prospective, multicenter NAC trial for patients with clinical stage II-III high-risk breast cancer. Patients are randomized to novel NAC agents, with pathologic complete response being the primary endpoint. As part of the trial, serial ctDNA is assessed with a highly sensitive tumor-informed assay using up to 16 patient-specific tumor mutations (Signatera) at baseline, 3 weeks, 12 weeks, and post-NAC. We determined whether ctDNA positivity or negativity post-NAC, and the change in ctDNA status baseline/post-NAC (-/-, -/+, +/+, +/-) are associated with ypN category (N0, N1, N2). Results: ctDNA status was available post-NAC in 495 patients and change in ctDNA status from baseline was available in 493. At baseline, ctDNA was detected in 160/220 (72.3%) cN0 patients and 227/273 (83.2%) cN+ patients (p=0.006). Post-NAC, ctDNA was detected in 11/220 (5%) cN0 patients and 34/273 (12.5%) cN+ patients (p=0.004). While baseline ctDNA status was not associated with ypN category, there was a significant association between post-NAC ctDNA status and ypN category. For ctDNA + patients post-NAC, 33.3% were ypN0, 31.1% were ypN1, and 35.6% were ypN2 at surgery; in contrast, for ctDNA - patients post-NAC, 67.1% were ypN0, 23.1% were ypN1, and 9.8% were ypN2 (p<0.0001). Dynamic ctDNA changes were also associated with ypN category, with significantly more ypN0 patients among ctDNA -/- or ctDNA +/- cases, and more ypN2 patients in those who did not clear ctDNA (+/+) (p=0.0001, Table). Conclusions: To our knowledge this is the first study to demonstrate a significant relationship between ctDNA and ypN category, which has important surgical implications. CtDNA negativity was associated with low likelihood of ypN2 disease, making these patients excellent candidates for SLN surgery or TAD. Ongoing analyses will incorporate receptor subtype and timing of clearance of ctDNA. CtDNA in breast cancer may help tailor surgical management of the axilla, potentially reducing patient morbidity without compromising prognostic information. ctDNA baseline/post-NAC ypN0 (n=317) ypN1 (n=116) ypN2 (n=60) ctDNA -/- (n=105) 72.4% 19.1% 8.6% ctDNA -/+ (n=1) 0.0% 100.0% 0.0% ctDNA +/+ (n=44) 34.1% 29.6% 36.4% ctDNA +/- (n=343) 65.9% 23.9% 10.2%

5041 Background: Prior studies suggest that chemotherapy-naïve pts with mCRPC treated with AA have a higher CV event-related hospitalization risk than those treated with ENZA. To further explore this association, this real-world, comparative causal inference study used a large US dataset to assess CV event risk in chemotherapy-naïve pts with mCRPC who initiated treatment (Tx) with ENZA or AA and provide outcome data based on history of (h/o) CV disease (CVD). Methods: Using US Medicare fee-for-service claims (Jan 2010–Dec 2022), we identified chemotherapy-naïve pts aged ≥65 years with mCRPC who initiated ENZA or AA between Sep 2014 and May 2017. The primary endpoint was a 4-point major adverse CV event (MACE-4; composite of acute myocardial infarction [AMI], stroke, unstable angina/revascularization [UA/R], and heart failure). Atrial fibrillation (AFib), venous thromboembolism (VTE), and all-cause death were also analyzed. Groups were propensity score matched (PSM) to adjust for differences in pt characteristics, assessed using standardized mean difference (SMD). Cause-specific Cox proportional hazards models were used to comparethe risk of CV outcomes between intention-to-treat cohorts, with death as a competing event. Subgroup analyses were conducted based on h/o CVD. Sensitivity analysis was performed with a MACE-5 endpoint, defined as MACE-4 or CV-related death. Results: Of 6319 pts in the total study population (ENZA: 2934; AA: 3385), 2913 PSM pts were included from each group. The ENZA and AA cohorts had similar baseline characteristics even before PSM (SMD<0.1), with a mean (standard deviation) age of 78.8 (7.3) years; 76% of pts had prior CVD. Compared with pts on ENZA, pts on AA had a significantly higher risk of experiencing MACE-4—particularly UA/R—as well as a higher risk of AFib and VTE (Table). Similar results were found in the subgroup of pts with a h/o CVD and the sensitivity analyses. Additionally, pts on AA had a higher risk of all-cause death than pts on ENZA, regardless of CVD history (h/o CVD hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.07–1.21, P =0.0001; no h/o CVD HR: 1.12, 95% CI: 1.01–1.26, P =0.036). Conclusions: This matched analysis of US Medicare beneficiaries showed an increased risk for MACE-4, AFib, and VTE in pts with mCRPC treated with AA compared to ENZA, in the overall pt population and pts with a h/o CVD. The risk of all-cause death was higher with AA in all pts. These findings provide insights into Tx decision-making for pts with mCRPC, especially those at high risk of CV events. Outcomes HR* (95% CI) P -value MACE-4 1.12 (1.02–1.24) 0.028 AMI 1.01 (0.76–1.32) 0.987 Stroke 0.92 (0.70–1.20) 0.505 UA/R 1.13 (1.01–1.26) 0.041 Heart failure 1.19 (0.90–1.58) 0.237 AFib 1.73 (1.31–2.29) 0.0001 VTE 1.37 (1.02–1.85) 0.037 All-cause death 1.13 (1.07–1.19) 0.0001 *ENZA = reference group.

5022 Background: Racial disparities are evident in PCa, with Black men experiencing a higher incidence and worse survival compared to NHW patients (pts). The molecular alterations that distinguish these groups remain incompletely characterized. Herein, we investigate the clinical-genomic features that potentially contribute to the differences in outcomes between Black and NHW pts with PCa. Methods: Comprehensive next-generation sequencing of DNA (592-gene panel/whole exome) and RNA (whole transcriptome) was performed at Caris Life Sciences on PCa tissue samples (n = 5,412), collected from 2015 to 2023. Transcriptomic signatures – Androgen Receptor (AR), Neuroendocrine PCa (NEPC) scores – were calculated. Real-world overall survival (OS) data was obtained from insurance claims and was analyzed using Kaplan-Meier estimation. Results: Overall, 1,078 pts with PCa identified as Black, while 4,334 were NHW. Black pts were younger at biopsy collection than NHW pts (median age 66 vs 71 years, P < 0.001). The proportion of metastatic samples was higher in Black pts compared to NHW pts (43% vs 38%, P < 0.01). The prevalence of castrated PCa specimens was similar between Black and NHW pts (26.0% vs 25.4%, P = 0.72). Among non-castrated PCa tumors, tumors from NHW pts had more frequent alterations in TP53 , PTEN , PIK3CA , and CHEK2 , while tumors from Black pts had more SPOP and CTNNB1 mutations. In the castrate setting, TP53 and PTEN alterations were more frequent in tissue samples from NHW pts, while CDK12 and SPOP mutations were more frequent in tumors from Black pts. TMPRSS2 fusions were more prevalent in the NHW cohort across both castrated and non-castrated tumors. Tumors from Black pts had higher FOLH1 / PSMA and STEAP1 expression, elevated AR scores, but lower CD276 / B7H3 expression and NEPC scores. In the overall cohort, Black pts demonstrated a shorter median OS from diagnosis compared to NHW pts (86 vs 94 mos, P = 0.03). Black pts had a significantly longer time on treatment with enzalutamide in both the non-castrate (HR 0.82, P= 0.04) and castrate subgroups (HR 0.77, P= 0.03). Among pts with homologous recombination repair (HRR) deficiency-harboring tumors, PARP inhibitors provided a numerically longer survival benefit in Black pts than in NHW pts (21 vs 13 mos, P = 0.09). Conclusions: This multi-institutional study reveals distinct molecular profiles between Black and NHW pts with PCa. Despite having molecular features associated with better prognosis, Black men demonstrated worse survival outcomes, pointing to multifaceted determinants of disease outcomes. Notably, Black pts had improved outcomes on enzalutamide and showed potential benefit from PARP inhibitors in the presence of HRR mutations. These findings highlight genomic differences in diverse PCa populations and suggest therapeutic opportunities to address outcome disparities.

5013 Background: There is no established role for the use of docetaxel with ADT and RT for HRLPC, with mixed results seen in prior RCTs. Prior work from ICECaP (Ravi et al, Eur Urol 2024) has shown that patients (pts) with very high-risk disease (i.e. 2 or 3 risk factors [RFs]: Gleason ≥8, PSA >20, ≥cT3 and/or cN1) have the poorest outcomes with RT+ADT for HRLPC, with 5-year metastasis-free survival (MFS) of ≤80%. We aimed to perform an IPD meta-analysis of the role of docetaxel with ADT+RT for HRLPC and specifically evaluate whether patients with very high-risk disease benefit from the addition of docetaxel. Methods: IPD from RCTs involving pts with HRLPC treated with RT+ADT +/- docetaxel collated by ICECaP were analyzed. “High-risk” disease was defined as presence of 1 RF and “very high-risk” disease as 2-3 RFs and/or cN1 disease. The primary outcomes of interest were MFS and overall survival (OS). Hazard ratios (HR) for MFS and OS were estimated using Cox regression, stratified by year of randomization and adjusted for age at randomization and ECOG performance status. 5-year MFS and OS rates were estimated using the Kaplan-Meier method. Subgroup analyses were performed according to the severity of disease (high- and very high-risk), and p-values for interaction were tested using the likelihood ratio test. Results: 1690 pts treated on 4 RCTs (GETUG-12, DFCI 05-043, STAMPEDE, RTOG-0521) between 2002-2015 were eligible. Median age was 65, median PSA was 23 (IQR 10-48); 154 (9%) pts had cN1 disease and 1444 (85%) received long-term ADT with RT. Median follow-up was 10 years (range: <1-15). Overall, the addition of docetaxel to RT+ADT was not associated with a significant benefit in MFS (HR=0.89 [0.76-1.05], p=0.160) or OS (HR=0.88 [0.74-1.05], p=0.167). Though there was some evidence for favoring docetaxel in pts with very high-risk disease (n=1054; MFS HR=0.86 [0.71-1.05]; OS HR=0.85 [0.68-1.07]) compared to high-risk disease (n=636; MFS HR=0.97 [0.74-1.27]; OS HR=0.95 [0.71-1.28]), there was no evidence of a significant difference in treatment effect by risk group (p-interaction >0.1). 5- and 10-yr MFS and OS in pts with high- and very high-risk disease, stratified by receipt of docetaxel, are shown in the Table. Conclusions: Some HRLPC pts with very high-risk disease may benefit from the addition of docetaxel to RT+ADT. Biomarker evaluation within this group may identify those who are candidates for treatment intensification with docetaxel with RT+ADT (+/- androgen receptor pathway inhibitors) in HRLPC. % (95% CI) High risk Very high-risk RT+ADT RT+ADT+docetaxel RT+ADT RT+ADT+docetaxel 5yr MFS 87 (82-90) 90 (86-93) 74 (71-78) 80 (76-83) 5yr OS 90 (86-93) 93 (90-96) 84 (80-86) 89 (86-92) 10yr MFS 67 (61-72) 71 (65-76) 51 (46-55) 55 (49-60) 10yr OS 74 (69-79) 77 (72-82) 62 (57-67) 67 (62-72)

e16001 Background: Esophageal carcinoma ranks among the top 10 malignancies in the world, contributing to high morbidity and mortality. With radiotherapy being one of the most administered treatment options, different variations of administration have evolved. Two such variations include intensity-modulated radiotherapy and 3D conformational radiotherapy. These modalities have been investigated for their efficacy and rate of adverse events. However, conclusions from the trials conducted have been variable. In this systematic review and meta-analysis, we aim to collate these findings to assess the exposure of cancerous cells and rates of adverse events following IMRT or 3D-CRT. Methods: A comprehensive literature search was conducted across three databases for all articles published from inception till September 2024. All primary studies evaluating the comparative efficacy of IMRT vs 3D-CRT were included. Outcomes assessed include dose volume histograms (DVHs) at heart and lung, Dmax at the spinal cord, and irradiation toxicity. Data analysis was conducted in RevMan 5.4 using a random-effects model. Results: A total of twenty records were included in the study, with a sample size of 3090 patients. Radiation dosage, estimated as DVHs, was equal across both regimens at heart (MD: 2.67; 95%CI: –0.15 to 5.48; P = 0.06), except at 40 Gy of radiation, where a lower DVH was noted among patients being administered IMRT (MD: 6.64; 95%CI: 0.25 to 13.03; P = 0.04). At the lung, a higher DVH was noted, especially for doses of 20 Gy or above, on using IMRT. Similarly, a lower dosage in the spinal cord was noted in the IMRT group (MD: 2.87; 95%CI: 1.04 to 4.70; P = .002). Consequently, a lower risk of esophagitis was noted among the IMRT group (OR: 1.54; 95%CI: 1.14 to 2.07; p = 0.009]). While considering patient outcomes, the odds of survival were higher in the IMRT group at 3 years post-treatment (OR: 0.53; 95%CI: 0.31 to 0.92; P = 0.02). Conclusions: IMRT was superior to 3D-CRT in terms of volume of tissue irradiated and lower spinal toxicity. A higher chance of survival was noted in the IMRT group. Further trials are needed to strengthen these findings. Outcome Mean Difference (MD) 95% confidence interval (CI) P value Mean dosage at lung 1.14 0.6, 1.68 <0.0001 Mean dosage at heart 2.67 -0.15, 5.48 0.06 Radiation esophagitis Odds ratio, OR: 1.38 1.09, 1.76 0.009 Radiation pneumonitis OR:1.37 0.62, 3.01 0.43 3-year OS OR: 0.69 0.56, 0.84 0.0003 5-year OS OR: 0.53 0.31, 0.92 0.02 Maximum dosage at spinal cord 2.87 1.04, 4.7 0.0002