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OBJECTIVE Chronic spinal degenerative diseases have been associated with reduced quality of life and dependency on others for personal needs and care. The change between preoperative and postoperative care dependency has yet to be explored in patients with cervical spondylotic myelopathy (CSM). In this retrospective study of a prospectively collected database, the authors evaluated the return to independence in performing self-care following surgical intervention for CSM. METHODS The CSM dataset of the Quality Outcomes Database (QOD) Spine CORe study group was queried. Care dependency was assessed using the personal care component of the Neck Disability Index (NDI) questionnaire, having an ordinal scale from 0 to 5, with 5 representing the inability to independently perform activities of daily living. Numeric rating scale (NRS) scores for arm pain and neck pain were recorded at a 24-months postoperative follow-up. Multivariable logistic regression analyses were performed to identify baseline risk factors for an inability to care for oneself and the symptoms leading to care dependency at 24 months postoperatively. Satisfaction with surgery was measured using the 4-point North American Spine Society (NASS) index. RESULTS Of the 1137 patients with CSM and baseline personal care scores, 167 (14.7%) were care dependent at baseline (NDI personal care score ≥ 3). Patients with care dependency at baseline were predominantly Medicare beneficiaries and had a high school or lower level of education. Long-term follow-up rates for this study were 82.5% for NDI, 84.8% for patient satisfaction with surgery, 82.4% for NRS arm pain, and 81.8% for NRS neck pain. Of the care-dependent patients, more than 80% became independently able to care for themselves by the 24-month follow-up. Patients with resolved care dependency at 24 months had demonstrated lower baseline NDI and NRS neck pain scores (p < 0.01 for both). Neck pain was significantly associated with care dependency at 24 months’ follow-up (p < 0.01). Patients who reported improvement in their ability to care for themselves noted higher postoperative satisfaction (NASS score 1–2) at the 3-month (89.4% vs 80.2%, p < 0.01) and 24-month (88.2% vs 67.4%, p < 0.01) follow-ups. CONCLUSIONS Fifteen percent of patients with CSM depended on others for care preoperatively. After surgery to treat CSM, 81.8% of those who had depended on others for care became independent. Patients with improvements in care dependency noted higher postoperative satisfaction at the 3-month and 24-month follow-ups. Patients with resolved care dependency on long-term follow-up had lower NDI and NRS neck pain scores at baseline. Surgery had a significant impact on patients’ attainment of independence.

8501 Background: TROPION-Lung02 (NCT04526691) evaluated the TROP2-directed antibody-drug conjugate (ADC) Dato-DXd plus pembro combination with or without Pt-CT in aNSCLC. Here we report primary analyses of pts receiving combination therapy in the 1L setting. Methods: Pts across 6 cohorts were dosed with Dato-DXd (4 or 6 mg/kg) plus pembro 200 mg alone (doublet) or with pembro plus Pt-CT (triplet; cisplatin 75 mg/m 2 or carboplatin AUC 5) Q3W. PD-L1 expression (tumor proportion score) was assessed locally by immunohistochemistry (22C3 assay). Primary objectives were safety and tolerability; efficacy was a secondary objective. Results: As of Apr 29, 2024, 96 pts received either the doublet (n=42) or triplet (n=54) combination as 1L therapy; 29% and 15% of pts were ongoing, respectively. Median ages were 65 (doublet) and 64 years (triplet). Median treatment durations were 9.7 and 5.8 months, respectively. Stomatitis (doublet, 57%; triplet, 33%) and nausea (doublet, 42%; triplet, 48%), primarily Gr 1–2, were the most common adverse events (AEs) across both regimens. Treatment related serious AEs occurred in 5 (12%) and 12 (22%) pts in each cohort and no deaths related to study drug were seen. Efficacy outcomes, including by histology, are summarized in the Table. Biomarker analyses, including efficacy by PD-L1 status, will be presented. Conclusions: In this largest data set to date evaluating an ADC combined with an anti-PD-1/L1 agent in the 1L setting, the combination of Dato-DXd plus pembro treatment both with and without Pt-CT elicited durable antitumor activity in pts with aNSCLC. Tolerability of the combinations was as expected, based on known profiles of the individual agents. Clinical trial information: NCT04526691 . All 1L (n=96) 1L, Nonsquamous (n=75) 1L, Squamous (n=21) Response, n (%) Doublet (n=42) Triplet (n=54) Doublet (n=33) Triplet (n=42) Doublet (n=9) Triplet (n=12) Confirmed objective response rate 23 (55) 30 (56) 17 (52) 24 (57) 6 (67) 6 (50) Complete response 1 (2) 2 (4) 1 (3) 2 (5) 0 0 Partial response 22 (52) 28 (52) 16 (49) 22 (52) 6 (67) 6 (50) Stable disease 14 (33) 18 (33) 12 (36) 14 (33) 2 (22) 4 (33) Progressive disease 3 (7) 2 (4) 3 (9) 1 (2) 0 1 (8) Disease control rate a 37 (88) 48 (89) 29 (88) 38 (91) 8 (89) 10 (83) Median duration of response, mo (95% CI) 20.1 (9.7–NE) 13.7 (5.7–NE) 24.9 (9.7–NE) 18.0 (8.0–NE) 12.0 (5.5–NE) 5.5 (4.1–NE) Median PFS, mo (95% CI) 11.2 b (8.2–21.3) 6.8 c (5.5–11.1) 11.2 (6.1–21.3) 10.8 (5.5–17.3) 10.2 (0.4–NE) 6.7 (1.0–8.2) a Proportion of pts with confirmed CR + PR + SD at 12 wks. b.c Median (95% CI) PFS follow-up, mo: b 17.3 (11.3−26.8); c 23.5 (17.3−27.9). mo, months; NE, not evaluable.

e14626 Background: Despite advancements in neoadjuvant therapy and surgical techniques, patients with pancreatic ductal adenocarcinoma (PDAC) often experience high recurrence rates after total neoadjuvant therapy (TNT) and resection. Existing tumor response scoring systems, such as the College of American Pathologists (CAP) guidelines, fail to stratify recurrence risk effectively, emphasizing the need for novel, objective approaches. Methods: This study evaluated spatial characteristics of residual cancer and stroma in a multi-site cohort of 203 patients with resected PDAC following TNT, not having achieved a major pathologic response (CAP 2 or 3). Whole slide images (WSI) of hematoxylin and eosin-stained sections were digitized and analyzed using artificial intelligence to perform tissue segmentation. Metrics quantifying spatial morphology and configuration, inspired by principles of landscape ecology, were computed to explore spatial features of the tumor microenvironment (TME). Statistical models (recursive partitioning and regression tree [RPRT] model and Cox model with backwards eliminations) incorporating these features were developed to stratify recurrence risk. Results: Five metrics were used for risk classification model build. Three models successfully classified patients into high- and low-risk groups based on spatial metrics. Models demonstrated moderate discriminatory power (C-statistics: 0.560–0.566) and showed that increased tumor fragmentation, like stromal patch density and cancer patch shape index, were strongly associated with improved outcomes. Conclusions: Integrating spatial metrics of cancer-stroma configuration enhances risk stratification beyond conventional scoring systems. Given increased tumor fragmentation is associated with improved outcomes, these data indirectly suggest ecological mechanisms of treatment resistance. This approach offers a pathway toward personalized post-operative management strategies to improve outcomes in PDAC. Risk classification models. Model Description Event/n Median DFS (95% CI) HR(95% CI) p-value C-statistics 1(RPRT) High risk: log standard deviation of the stroma shape index > 0.651 87 / 101 8.22(5.72 – 10.1) 1.64(1.20 – 2.25) 0.002 0.562 Low risk: log standard deviation of the stroma shape index ≤ 0.651 71 / 102 11.90(9.24 – 25.1) Ref 2(RPRT) High risk: log standard deviation of the stroma shape index > 0.651 & mean cancer shape index ≤ 1.775 58 / 63 7.23(5.19 – 9.63) 1.82(1.31 – 2.52) 0.0003 0.560 Low risk: (log standard deviation of the stroma shape index > 0.651 & mean cancer shape index > 1.775) or log standard deviation of the stroma shape index ≤ 0.651 100 / 140 11.57(9.24 – 17.92) Ref 3(Backwards elimination) High risk: PI * > median 86 / 101 8.02(6.08 – 9.86) 1.73(1.26 – 2.37) 0.0007 0.566 Low risk:PI * ≤ median 72 / 102 15.72(9.97 – 25.05) Ref *PI: (0.2701 * log mean stroma area) + (0.3905 * log edge density).

e18508 Background: BPDCN is a rare and aggressive hematologic malignancy. Despite the advent of targeted therapies, median overall survival (mOS) remains <1 year (y) in the absence of stem cell transplant (SCT). This study evaluates clinical and molecular predictors of outcomes in a large cohort of BPDCN patients at a tertiary center. Methods: BPDCN patients seen at Mayo Clinic (AZ, FL, MN) between 2000-2024 were identified retrospectively. Analyses considered parameters at diagnosis. Next generation sequencing (NGS) was performed using a 47-gene assay. Standard statistical methods were used; calculations used R. Results: Among 69 patients, the median age was 70y (range 19-94) with male predominance (83%). At presentation, skin (80%), bone marrow (73%), lymph nodes (52%), spleen (27%), and CNS (12%) were involved; 26% had a concurrent hematologic malignancy. Among 20 cases with NGS, the median number of mutations was 3 (range 0-5), most frequently TET2 (n=16), ASXL1 (n=13), SRSF2 (n=7), and NRAS (n=5). Frontline therapy (Table) yielded a complete response (CR) rate of 63% and overall response rate of 76%. CR rates were similar among regimens, but patients who received an ALL (hyper-CVAD based) regimen (8/13) or tagraxofusp (6/9) were more likely to be bridged to SCT (6/29, p<0.01). After median follow up of 38 months (mo), mOS for all was 15 (95% CI 12-21) mo; 44 (64%) were deceased at last follow up. Among 62 evaluable patients, 20 (32%, median age 60 vs 74y, p<0.01) underwent SCT which improved survival (mOS 51 vs 10 mo, 3y OS 52% vs 5%, p<0.01); mOS was not different between allogeneic (n=17) and autologous (n=3) SCT (54 vs 38 mo, p=0.45). When censored for SCT, the 1y OS for patients receiving an ALL regimen, tagraxofusp, or other regimen was 82%, 67%, and 47%, respectively (p=0.15). In univariate analysis, age ≥50y, lymph node involvement, bone marrow involvement, hemoglobin <10 g/dL, leukocytes (WBC) >11 x10 9 /L, abnormal karyotype, and HCT were significantly associated with OS. In multivariate analysis, WBC >11 x10 9 /L (HR 3.7, p<0.03), abnormal karyotype (HR 5.4, p<0.01), and SCT (HR 0.23, p<0.01) remained significant. Separately, SRSF2 mutation was associated with inferior OS (15 vs 51 mo, p=0.02), but significance was lost when adjusted for age, abnormal karyotype, and SCT. Conclusions: Newly-diagnosed BPDCN patients treated with an ALL regimen or tagraxofusp followed by SCT had longer OS compared to those treated with all other regimens. WBC >11 x10 9 /L and abnormal karyotype were independent predictors of inferior survival whereas SCT was beneficial. Regimen N Age (y) ANNOVA CR Chi Sq HCT Chi Sq 1y OS mOS (mo) Log-rank Tagraxofusp 9 68 (40-70) <0.001 7 (78%) 0.548 6 (67%) 0.018 88% 20.8 0.121 ALL 13 43 (20-72) 8 (67%) 8 (62%) 74% 50.7 Hyper-CVAD 11 43 (20-72) 6 (60%) 6 (60%) 67% 35.8 AML 18 70 (48-80) 13 (76%) 5 (28%) 58% 14.2 Intensive 8 66 (48-77) 7 (88%) 3 (38%) 57% 12.4 HMA+Venetoclax 8 69 (65-80) 6 (75%) 2 (25%) 50% 14.0 Lymphoma 8 74 (49-85) 3 (43%) 1 (13%) 50% 14.0 CHOP 6 74 (49-85) 3 (50%) 1 (17%) 50% 17.7 Other 3 66 (63-73) 1 (33%) 0 (0%) 33% 12.0

e12568 Background: Modern preventive screening have made it possible to identify ductal carcinoma in situ (DCIS). Progression of DCIS to invasive disease is known to be driven by somatic evolution and affected by clinical interventions. Yet studies indicate that only 20–30% of the cases of DCIS will progress further if not treated, implying that a large portion of patients are over treated. Recognizing which pre-cancerous tumors are likely to progress to cancer or recur as DCIS after initial treatment is of great importance to optimize treatment options, lower associated risks and allocate healthcare efforts to patients that most benefit from early treatment. Methods: This study consists of a retrospective cohort of 158 patients, 57 of which had a DCIS recurrence over 2 to 228 months after treatment, and 45 progressed to invasive disease over 12 to 180 months. We generated a digital pathology library consisting of hematoxylin and eosin (H&E) stained whole slide images (WSI), and applied machine learning methods to perform duct and nuclear segmentation followed by cell classification. We then computed a set of spatial statistics from landscape ecology to characterize each sample. We used LASSO on half of the data (the training set) to select a Cox proportional hazards model that predicted recurrence of DCIS or cancer and used the other half of the data (the test set) to validate the predictors in the Cox model. Results: When considering the time to recurrence as disease-free survival (DFS), the type of DCIS treatment stratifies patients between Lumpectomy Only and More than Lumpectomy groups (log-rank test p-value < 0.0001), recapitulating previous results. When the subset of patients that had more than a lumpectomy was analyzed using spatial landscape ecology metrics, a decrease in the interaction between tumor cells and fibroblasts and between tumor cells and lymphocytes, measured by the mean nearest neighbor distance, were associated with improved DFS (concordance = 0.717) in the model validation set. Stratification of samples by the median risk is discriminatory with a p-value < 0.001. Alternatively, decreased nearest neighbor distance between lymphocytes and fibroblasts was associated with the time to invasive disease (p-value < 0.05). Conclusions: Integrating spatial ecological statistics of cell distributions enhances risk stratification of DCIS samples beyond the known effects of early treatment. Our results highlight the importance of ecological mechanisms in recurrence, progression and treatment resistance. The risk associated with spatial interactions of lymphocytes and fibroblasts suggests previously unknown ecological interactions may be associated with early micro-metastases that result in breast cancer even after mastectomy or lumpectomy with radiation in patients with DCIS.

3069 Background: Molecular targeted agents have revolutionized cancer diagnosis and treatment. Intraoperative molecular imaging (IMI) is a novel technique that entails performing real-time, in vivo optical imaging during surgery to ensure cancer clearance. A multicenter clinical trial was conducted using abenacianine, a cathepsin targeted near-infrared (NIR) IMI agent to visualize pulmonary nodules during surgery. The primary objective was to assess the efficacy of abenacianine in localizing pulmonary lesions, evaluating surgical margin, and identifying unsuspected disease. Methods: Participants scheduled to undergo surgery for known or suspected cancer in the lung received abenacianine (0.32 mg/kg intravenous) preoperatively 12 to 36 hours before surgery. During a standard-of-care surgery, the lung underwent IMI and additional disease not identified by conventional methods were identified and analyzed. Efficacy was measured by frequency of clinically significant events (CSEs) defined as localization of lesions not found by standard surgical techniques, identification of additional cancers, identification of positive surgical margins confirmed by histology, and detection of cancerous lymph nodes. Results: 89 participants were included in the study. The mean age was 67 years and 57 (64%) were female. Of 89 participants administered abenacianine who underwent standard of care surgical resection for known or suspected cancer in the lung, 40 (45%) had at least one CSE. Abenacianine with NIR imaging identified lesions that were not found by standard surgical methods in 34 (38%) participants, synchronous and occult cancers that were not found by pre-operative imaging in 2 (2%), margins within 10 mm of the closest staple line in 8 (9%), and lymph nodes determined to be cancerous in 1 (1%) participant. Tumors visualized by IMI with abenacianine included non-small cell lung cancers (adenocarcinoma, squamous cell carcinoma, neuroendocrine tumor) and cancers that metastasized to the lung (breast, colorectal, prostate, thymoma, renal cell, sarcoma). Abenacianine was safe and well tolerated in this study; there were no drug-related serious adverse events. Conclusions: This Phase 2 multicenter study demonstrated that using IMI with abenacianine during standard-of-care lung cancer surgery markedly improved clinical outcomes. Abenacianine localized tumors intraoperatively, identified synchronous and occult lesions, helped assess negative margin status, and identified cancerous lymph nodes enabling a more complete oncologic resection. Clinical trial information: NCT06145048 .

7032 Background: The impact of immune cell counts pre LD and during immune reconstitution on CAR T therapy outcomes is poorly understood. We investigated the association between CD4, CD8 and NK cell counts and CAR T therapy outcomes in patients with LBCL. Methods: Retrospective study of R/R LBCL patients who received CAR T cells between 2016-24 at Mayo Clinic, Rochester, were included in this analysis. Peripheral blood CD4, CD8 and NK counts were measured pre LD and at M1 post CAR T infusion. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff for pre LD and M1 immune cells to predict patients who were alive and in remission at 6 months (M6) post CAR T infusion. Patients who progressed or were lost to follow up prior to day 30 were excluded from M1 ROC analysis. Results: Of 140 patients, 81 were alive and in remission at M6 (Group A), while 59 had relapse or death (Group B). Axicabtagene ciloleucel was the CAR T product given in 81% of patients (114/140). Median pre LD CD4 counts were significantly lower in Group B compared to group A (143 vs 280 cells/µL, p = 0.001). No significant difference was observed in median pre LD CD8 counts (205 vs 221 cells/µL, p = 0.8). ROC analysis identified an optimal pre LD CD4 count of 124.5 cells/µL for M6 alive+remission. Lower pre LD CD4 counts (<124.5) predicted worse progression free survival (PFS) in univariate (HR = 3.02, 95% confidence interval [CI]: 1.73–5.27, p< 0.01) and multivariable analysis (MVA) adjusted for IPI and the number of prior lines (aHR = 2.54, 95% CI: 1.39–4.62, p< 0.01).Lower pre LD CD4 counts also predicted inferior overall survival (OS) in MVA (aHR = 2.27, 95% CI: 1.08–4.77, p = 0.03). (Table 1) On day 30 landmark analysis, ROC identified M1 optimal CD4 count of ≥ 99.5 cells/µL to be associated with a trend toward superior PFS (P=0.09), but not OS (p=0.90) in MVA. Median pre LD NK cell counts were significantly lower in Group B (73 vs 98 cells/µL, p = 0.04). ROC analysis identified an optimal pre LD NK count of 151 cells/µL for M6 alive + remission. Lower pre LD NK counts (<151) predicted worse PFS, both on univariate (HR = 4.17, 95% CI: 1.29–13.47, p = 0.02) and MVA (aHR = 4.64, p< 0.01). The lower pre LD NK cell count group had worse OS in MVA (aHR = 5.69, 95% CI: 1.16–28.1, p = 0.01). (Table 1) On D30 landmark analysis, M1 NK cell count of ≥ 128.5 cells/µL was associated with a trend toward superior PFS (P=0.08), but not OS (p=0.30) in MVA. Conclusions: Pre LD CD4 and NK cell counts are significantly associated with PFS and OS post CAR T therapy in patients with R/R LBCL. Pre-treatment immune subset levels may identify patients at higher risk of relapse or death after CAR-T therapy. Groups Median PFS 2 Year PFS Median OS 2 Year OS CD4 ≥124.5 cells/µL (N=75) NR 58% 3.31 years 67% CD4 <124.5 cells/µL (N=30) 2.2 months 22% 1.59 years 45% NK ≥151 cells/µL (N=17) NR 77% NR 84% NK <151 cells/µL (N=82) 10.6 months 44% 3.31 years 62%

3116 Background: Pralsetinib is an oral tyrosine kinase inhibitor that selectively and potently targets oncogenic RET fusion and mutation proteins. RET fusions or mutations are present in various tumor types. We report the final results from the phase 2 portion of ARROW, a phase 1/2, open-label, multi-cohort, dose-expansion study evaluating the efficacy and safety of pralsetinib (NCT03037385) in patients with RET fusion-positive solid tumors other than non-small-cell lung cancer (NSCLC) and thyroid cancer. Methods: Eligible pts were ≥18 years of age with a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion or mutation, had previously received standard of care appropriate for their tumor type, and were not eligible for any other study groups. Overall response rate (ORR) and safety were primary endpoints of the study. Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). The final database lock was May 20, 2024. Results: Twenty-nine patients were enrolled with 11 different solid tumor histologies. Twenty-six (90%) received prior systemic therapy. Median age was 58 years (range 25-75); 59% were female. Twenty-eight patients were included in the efficacy analysis. ORR (by RECIST) was 46.4% (13/28); 10.7% (3/28) achieved complete response (pancreatic cancer, n=2; cancer of unknown primary, n=1) and 35.7% (10/28) achieved partial response. Median PFS was 7 months (95% CI: 3.9, 12.8). Median DOR was 11.1 months (95% CI: 5.5, 25.1). Median OS was 10.3 months (95% CI: 6.8, 25.2). Twenty-five (86%) patients experienced treatment-related adverse events (TRAEs); 19/29 (66%) reported TRAEs ≥grade 3. The most common TRAEs included increased aspartate aminotransferase (11/29; 38%), increased alanine aminotransferase (10/29; 35%), and anemia (9/29; 31%). Four (13.8%) patients experienced hypertension, and 1 (3.4%) patient had ≥grade 3 hypertension. No new safety risks were identified; AEs remained manageable with supportive care and/or dose modifications. Conclusions: In the phase 2 portion of this trial, responses were observed in many tumor types (Table). Pralsetinib demonstrated robust and durable anti-tumor activity with an ORR of 46.4%. These data validate RET fusions as a tissue-agnostic target with sensitivity to RET inhibition and activity beyond NSCLC and thyroid cancer, further supporting the promising potential of pralsetinib to address the unmet medical need in these patients. Clinical trial information: NCT03037385 . Overall response rate by tumor type. Cancer Type (patient n) ORRn (%) Pancreatic (5) 5 (100) Cancer of unknown primary (1) 1 (100) Neuroendocrine (3) 2 (67) Sarcoma (3) 2 (67) Head and neck (2) 1 (50) Small cell lung (2) 1 (50) Hepatobiliary (4) 1 (25) Colorectal (5), gastric (1), ovarian (1), thymic (1) 0

AbstractObjectiveThe effects of brain stimulation for diseases like epilepsy are delayed, making stimulation optimization difficult. The parameters for anterior thalamic nuclei (ANT) deep brain stimulation (DBS) for focal drug‐resistant epilepsy management are often restricted to those used in the SANTE landmark trial. There is little evidence regarding effective alternatives, and low‐frequency stimulation is typically neglected. We prospectively compare a widely differing stimulation parameter set to typical settings.MethodsThis randomized, modified crossover, open trial compares the efficacy and safety of an alternative set of parameters using continuous low‐frequency stimulation (cLFS) with a longer pulse width (7 Hz, 200 μs, continuous) compared to SANTE's intermittent high‐frequency stimulation (iHFS) with a short pulse width (145 Hz, 90 μs, cycling 1 min on/5 min off). After 3 months on a randomly assigned first set, patients are switched to the other settings, unless seizure‐free. Patients are re‐evaluated after 3 more months, which marks the completion of the trial. After that, they can either remain on the same settings or switch back.ResultsSixteen patients with a median baseline seizure frequency of 13.8 seizures/month (interquartile range [IQR] = 2.7–22.8) were included in the analysis. At trial completion (median follow‐up = 30 weeks, IQR = 26–35), ANT‐DBS significantly reduced median seizure frequency (62%, IQR = 18–81, Wilcoxon test statistic [W] = 99, p = .008). Both iHFS (33%, IQR = 0–65, W = 81, p = .02) and cLFS (73%, IQR = 30–79, W = 105, p = .001) significantly reduced median seizure frequency. cLFS showed improved median seizure frequency reduction compared to iHFS (W = 63, p = .03) and was not associated with any moderate or severe adverse effects.SignificanceResults support cLFS for ANT‐DBS as a safe and effective alternative to typical iHFS parameters. Stimulation with widely differing parameter sets may be as effective as or, in some situations, more effective than typical stimulation parameters.

OBJECTIVE Cervical spondylotic myelopathy (CSM) is often accompanied by neck pain, which, along with more recognized neurological deficits like motor and sensory changes, significantly impacts patients’ quality of life. The authors examined whether age influences improvements in neck disability and related quality-of-life measures after surgery for CSM. Using the Neck Disability Index (NDI) as the primary outcome, they compared long-term outcomes at 24 months among patients aged ≥ 65, ≥75, and < 65 years, exploring the effects of surgical intervention on both pain-related disability and functional recovery in older adults. METHODS Using the Quality Outcomes Database, the authors conducted a detailed propensity score–matched analysis on cohorts aged ≥ 65 and ≥ 75 years compared with a < 65-year-old cohort while controlling for baseline NDI scores, other demographic variables, health status, underlying pathology, number of levels, indication for surgery, surgical approach, and type of surgery. Differences in NDI total and subdomain scores at 24 months postoperatively were the primary measures of improvement. Age-related variability in NDI differential was assessed. EQ-5D and calculated SF-6D were secondary measures. RESULTS Of the 1141 patients in the cohort (January 2016 to December 2018), 687 patients were < 65 years, 325 were 65 to < 75 years, and 129 were ≥ 75 years of age. After propensity score matching, 197 patients each were well matched in the ≥ 65-year (mean 71.4 years) and < 65-year (mean 55.3 years) cohorts; similarly, 57 patients each were matched in the ≥ 75-year (mean 78.3 years) and < 65-year (mean 55.8 years) cohorts. Improvements in NDI scores and subdomain scores, EQ-5D, and calculated SF-6D were consistent at 3, 12, and 24 months postoperatively across all cohorts. At 24 months, patients ≥ 65 years showed NDI score improvements (−14.7 ± 22.3) similar to those < 65 years (−13.0 ± 21.3, p = 0.454), and patients ≥ 75 years demonstrated NDI improvements (−15.0 ± 19.7) comparable to those < 65 years (−17.6 ± 20.4, p = 0.499). A sensitivity analysis for linear relationship found that NDI improvement was statistically greater in older patients (7.5 points every 30 years, p < 0.0001), but this difference was below the minimal clinically important difference. Other clinical outcomes were similar between cohorts. CONCLUSIONS Surgical intervention for CSM yields substantial and similar improvements in NDI scores and other metrics among various age groups, including those aged at least 65 and 75 years. These results highlight the effectiveness of surgery across a broad patient demographic, underscoring its value in treating CSM irrespective of age.