Cheville, Andrea L.

e23276 Background: More than 50,000 patients with cancers of all stages were enrolled in the E2C2 trial, which captured patient-reported data across 6 symptom domains (SPPADE): sleep, pain, impaired physical function, anxiety, depression, and energy deficit or fatigue. This trial offers a unique opportunity to evaluate the evolution of symptom burden as prostate cancer (PCa) advances and the association of symptom burden with prognosis in the various disease states. Methods: The cohort was derived by cross-referencing participants in the E2C2 study with the Mayo Clinic Cancer Registry for more granular data on disease state and treatment characteristics, focusing on PCa. Symptoms were patient-reported on a 0-10 numerical rating scale, categorized as none/mild (0-3), moderate (4-6), and severe (7-10). We compared the prevalence of symptom burden across disease states, using the first survey completed by patients, in 3 groups: (1) non-metastatic (localized, locally advanced, and biochemically recurrent), (2) metastatic hormone sensitive (mHSPC), and (3) castration resistant (CRPC), using chi square tests. We then used log-rank tests to compare survival distributions based on symptom severity within each disease state. Results: A total of 1,011 patients were included. The distribution of moderate to severe symptoms by disease state is shown in Table 1. Fatigue, impaired physical function, and pain were more prevalent in patients with advanced disease, whereas the prevalence of depression and anxiety was not statistically different by disease state. Greater fatigue and physical impairment were consistently associated with poorer OS across all disease states, including patients with non-metastatic disease (p < 0.001). Pain was most strongly associated with inferior outcomes in the more advanced disease states of mHSPC (p < 0.001) and CRPC (p < 0.001). Anxiety (p < 0.001) and depression (p = 0.001) were only prognostic in CRPC patients. Conclusions: SPPADE symptoms are common in PCa. Physical symptoms are greater in more advanced disease, yet the high burden of unmet psychologic needs is similar across the disease states. Notably, severe patient-reported fatigue and physical dysfunction are strongly prognostic even in early disease, suggesting they are markers of physiologic vulnerability. Structured symptom monitoring may improve the identification of high-risk patients. Clinical trial information: NCT03892967 . Moderate to severe symptoms by disease state. Non-Metastatic (N= 243) mHSPC (N= 479) CRPC (N= 289) P-value Pain, n (%) 51 (21.3) 121 (25.5) 100 (35.1) 0.001 Fatigue, n (%) 92 (38.3) 230 (48.6) 163 (57.2) <0.001 Impaired Physical Function, n (%) 79 (32.5) 180 (37.7) 146 (50.7) <0.001 Sleep Disturbance, n (%) 72 (30.1) 167 (35.2) 104 (36.1) 0.3 Depression, n (%) 47 (19.6) 92 (19.4) 63 (22.0) 0.67 Anxiety, n (%) 56 (23.4) 93 (19.6) 68 (23.9) 0.3

1587 Background: Rehabilitation services (physical medicine and rehabilitation [PM&R], physical therapy [PT], occupational therapy [OT], and speech-language pathology [SLP]) improve physical function, symptom burden, and quality of life for cancer survivors, yet utilization remains low due to persistent barriers. The collaborative care model–based Enhanced Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) pragmatic trial improved symptom burden and palliative care utilization. Using post hoc exploratory analyses of population-level trial data, we evaluated whether this EHR-facilitated approach also increased rehabilitation service use. Methods: E2C2 was conducted across Mayo Clinic Midwest medical oncology practices using an unblinded, stepped-wedge, cluster-randomized cohort design. The EHR-embedded intervention targeted SPPADE symptoms (sleep interference, pain, impaired physical function, anxiety, depression, and fatigue). Symptoms and physical function were assessed using 11-point numerical rating scales linked to oncology encounters. Patients received self-management materials for moderate symptoms (4–6/10) and care manager support for severe symptoms (7–10/10). All outpatient rehabilitation encounters across the Mayo Clinic Enterprise were abstracted. Mixed-effects Poisson models estimated intervention effects on rehabilitation visits during the first 365 days of exposure. Results: Between March 28, 2019, and January 31, 2023, 50,207 patients were enrolled. Intervention and control conditions included 31,719 and 28,938 patients, respectively, with 10,450 contributing data to both periods. Cross-sectionally, 25% of participants reported moderate and 9% severe physical function impairment. Of 91,220 rehabilitation encounters scheduled, 57,669 (63.3%) were completed. Completed encounters were predominantly PT (68.3%), followed by OT (16.4%), physician visits (9.4%), and SLP (4.2%). The intervention was associated with a more than fourfold increase in completed rehabilitation encounters during the six weeks following index symptom assessment (adjusted mean 2.22 [95% CI, 0.14–4.29] vs 0.54 [0.40–0.68]; incidence rate ratio 4.11 [1.43–11.82]; P =0.009). Scheduled encounters also favored the intervention but did not reach statistical significance. Conclusions: An EHR-embedded symptom surveillance intervention increased short-term rehabilitation service completion, but overall utilization remained low relative to the prevalence of physical function impairment, highlighting the need for system-level strategies to translate symptom identification into sustained rehabilitation engagement.

1584 Background: Decades of evidence demonstrate that patients across the cancer continuum may benefit from validated rehabilitation services, yet delivery remains inconsistent. Prior reports of underuse have largely relied on small, single-site cohorts and have lacked population-level estimates of service need, referral, and visit completion, contributing to the assumption that provider reluctance to refer is a primary driver. Using post hoc exploratory analyses of population-level trial data, we evaluated patient- and system-level factors associated with non-use of rehabilitation services. Methods: This secondary analysis used data from the Enhanced Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) pragmatic trial, an unblinded, stepped-wedge, cluster-randomized cohort study comparing an EHR-embedded symptom surveillance and management system with usual care. All patients receiving care in Mayo Clinic Midwest medical oncology practices were enrolled regardless of cancer stage or phase. Symptoms and physical function were assessed using 11-point numerical rating scales linked to oncology encounters. Sociodemographic and clinical characteristics and all outpatient rehabilitation encounters across the Mayo Clinic Enterprise were extracted from the EHR. Rates and types of completed, canceled, and no-show rehabilitation encounters were examined. Results: Between March 28, 2019, and January 31, 2023, 50,207 patients were enrolled; 34% reported moderate or severe physical function impairment during follow-up. Despite this, only 8,818 patients (17.6%) completed at least one rehabilitation encounter. Of 91,220 encounters scheduled, 57,669 (63.3%) were completed (mean 6.5; median 3 per participant), leaving a substantial proportion canceled or no-showed (n=33,523, 36.7%). Completed encounters were predominantly physical therapy (68.3%), with fewer occupational therapy (16.4%), physician (9.4%), and speech therapy (4.2%) visits. Encounters were concentrated among patients with breast, hematologic, gastrointestinal, and genitourinary cancers. Completion was more likely among patients who were older, female, partnered, retired, and federally insured, whereas cancellations and no-shows were more common among younger, racial or ethnic minority, urban, unpartnered, employed, college-educated, and commercially insured patients (all P <0.001). Virtual visits and encounters in community (vs academic) settings were more likely to be completed (all P <0.001). Conclusions: A substantial gap persists between cancer survivors’ rehabilitation needs and service receipt, varying by cancer type and sociodemographic factors. High cancellation and no-show rates suggest that underuse extends beyond referral and underscore the need for redesigned, more accessible rehabilitation delivery models.

12007 Background: YAs with cancer, defined as those diagnosed prior to the age of 40, may experience greater symptom burden compared to those diagnosed at older ages. We evaluated the impact of an ePROM-triggered, CC-based, supportive care intervention on symptom burden in YAs with cancer. Methods: The Enhanced, Electronic Health Record-facilitated Cancer Symptom Control (E2C2) trial was a cluster-randomized, pragmatic trial (NCT03892967) that enrolled oncology patients seen at Mayo Clinic Rochester and within the Mayo Clinic Health System (sites in Minnesota and Wisconsin) between March 2019 and January 2023. Patients routinely reported the severity of six SPPADE symptoms (Sleep deficit, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue) on 11-point numerical rating scales. Symptom severity was classified as none to mild (0-3), moderate (4-6), or severe (7-10). Those with moderate or severe symptoms were offered symptom management education, while those with severe symptoms were also offered the option to work virtually with a symptom care manager. In this post hoc analysis, we examined the effects of the intervention on change in symptom scores among YAs and time to improvement to a mild/moderate level in those with at least one severe symptom. Results: Among 40,659 patients who responded to at least one survey, 2,598 were YAs and 38,061 were adults ≥ 40 years. Among YAs, 10.7%, 24.3%, and 65.1% were 18-24 years, 25-31 years, and 32-39 years, respectively. A greater proportion of YA patients were female (61.5% vs 57.0%), of a non-white race (12.4% vs 5.3%), living in an urban setting (65.7% vs 55.1%), single (36.4% vs 9.6%), on non-government insurance (78.1% vs 36.6%), employed (72.6% vs 37.4%), and had a Bachelor’s degree or greater (37.8% vs 28.3%, p < 0.001 for all). Fewer YA patients had metastatic disease compared to older patients (24.2% vs 35.2%, p < 0.001). Compared to a pre-intervention baseline, the mean change in symptom score for YA patients following the intervention demonstrated improvements in anxiety (-0.195) and depression (-0.168, p < 0.0001 for both), while physical function impairment worsened over the intervention period (0.101, p = 0.014). Compared to adults ≥ 40 years, YAs experienced greater intervention effects for management of depression ( p < 0.001), fatigue ( p = 0.01), pain ( p < 0.0001), and physical function impairment ( p < 0.0001). Among YAs with a severe symptom during the intervention period, median time to improvement to a mild/moderate level was longer for anxiety compared to those ≥ 40 years (3.5 vs 2.7 months, p = 0.009). Conclusions: Routine ePROM surveillance, coupled with CC-based symptom management, led to improvements in anxiety and depression among YAs with cancer, although, time to improvement was longer for anxiety compared to adults ≥ 40 years.

142 Background: LuPSMA is a life-prolonging radioligand therapy that is widely considered to have favorable tolerability. SPPADE symptoms (Sleep disturbance, Pain, Physical dysfunction, Anxiety, Depression, low Energy) are common in prostate cancer, yet data on patient-reported outcomes with LuPSMA in real-world settings remain limited. Methods: The E2C2 study (NCT03892967) evaluates the impact of a collaborative care intervention on patient-centered outcomes and healthcare utilization. This analysis includes mCRPC patients who initiated LuPSMA at Mayo Clinic (June 2022-July 2023) and completed at least one symptom survey within 6 weeks before or 2 weeks after the first LuPSMA treatment (baseline survey). SPPADE symptoms were rated on 0-10 scales; scores of 4-6 indicate moderate and 7-10 severe burden. A composite z-score was derived by standardizing each SPPADE domain to the cohort mean and averaging z-scores across domains per patient. Patients were stratified by composite symptom burden using cohort median and upper-tertile cutoffs. Associations with PSA50 response and overall survival (OS, from start of LuPSMA) were assessed using chi-square and Kaplan-Meier methods. In a longitudinal subgroup of patients completing a baseline survey plus at least one additional PRO survey while receiving LuPSMA (≥2 surveys), scores were compared from baseline to best during-treatment using Wilcoxon and Mann-Whitney U tests. Results: Of 373 patients starting LuPSMA, 51 patients met inclusion criteria. Median age was 71 years, 31% had visceral metastases, and median baseline PSA was 42.1 ng/mL. Overall, 85% of patients reported at least one moderate symptom and 46% at least one severe symptom. The most common moderate-to-severe symptoms were low energy (58%), pain (52%), and sleep disturbance (49%). Using an upper-tertile cutoff of the composite SPPADE score, 17 patients had high and 34 had low/moderate symptom burden prior to LuPSMA. PSA50 response was achieved in 17.6% of patients with high vs 47.1% with low/moderate composite symptom scores (p = 0.08). Median OS was 9.2 vs 16.7 months for high vs low symptom groups (p = 0.15, median split). The longitudinal subgroup included 24 patients with serial ePRO assessments while on LuPSMA. Composite SPPADE scores improved from baseline to the best during-treatment assessment in both PSA50 responders (n=10) and non-responders (n=14), with median composite z-score Δ of 0.35 vs 0.20, respectively (p = 0.68). Conclusions: Among patients with mCRPC receiving LuPSMA, baseline SPPADE symptom burden was high. Though not statistically significant in this underpowered cohort, PSA response and OS were numerically inferior in those with higher baseline burden. These findings suggest that ePRO-captured symptom burden may provide prognostic and patient-centered insights beyond traditional clinical variables. Clinical trial information: NCT03892967 .