McClelland PH, Satyadi MA, Johnson RP
… +10 more, Jacob R, Pan J, Rai J, Rai S, Sohal D, Olowokure O, Kharofa J, Wilson GC, Patel SH, Ahmad SA
Ann Surg Oncol
· 2026 Jun · PMID 42319588
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BACKGROUND: Neoadjuvant therapy (NAT) is increasingly used for resectable and borderline-resectable pancreatic ductal adenocarcinoma (PDAC), yet interpretation of treatment response remains challenging. PATIENTS AND METH...BACKGROUND: Neoadjuvant therapy (NAT) is increasingly used for resectable and borderline-resectable pancreatic ductal adenocarcinoma (PDAC), yet interpretation of treatment response remains challenging. PATIENTS AND METHODS: A single-center retrospective review was conducted of patients with resectable or borderline-resectable PDAC treated with multiagent NAT between 2008 and 2024. Radiographic response was assessed using RECIST 1.1 criteria, biochemical response by serum CA 19-9 reduction, and histopathologic response by College of American Pathologists (CAP) score. Primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS: Among 166 patients, 148 (89%) completed NAT and 121 (73%) underwent resection. After NAT, radiographic response was uncommon: 27% had tumor regression, 66% stable disease, and 7% progressive disease. By contrast, 83% achieved ≥ 45% CA 19-9 reduction after NAT, and 74% demonstrated histopathologic response after resection, including 8% complete pathologic response. Among resected patients with radiographically stable/progressive disease, 88% had biochemical response and 68% at least partial histopathologic response. Neither radiographic nor biochemical response were significantly associated with improved PFS or OS. Histopathologic response (CAP 0-2) was associated with improved PFS/OS on univariable analysis as well as improved PFS on multivariable analysis [adjusted hazard ratio (aHR) 0.57, 95% confidence interval (CI) 0.34-0.96; p = 0.034]. Isolated unresectable local progression during NAT was rare (n = 2). CONCLUSIONS: While imaging response and downstaging can occur with NAT, histopathologic response is more predictive of long-term survival and often occurs despite stable or progressive disease on imaging. Isolated unresectable local progression after NAT is rare, though broader treatment-related attrition remains a consideration in neoadjuvant sequencing.
Gervais C, Brouillette K, Benzouak T
… +4 more, Altuntur SK, Prakash I, Wong SM, Meterissian S
Ann Surg Oncol
· 2026 Jun · PMID 42315709
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BACKGROUND: Timely surgery is a key determinant of breast cancer outcomes; however, prior studies are inconsistent due to heterogeneous treatment pathways and inclusion of neoadjuvant therapy populations. The prognostic...BACKGROUND: Timely surgery is a key determinant of breast cancer outcomes; however, prior studies are inconsistent due to heterogeneous treatment pathways and inclusion of neoadjuvant therapy populations. The prognostic impact of delays to upfront surgery remains unclear. We evaluated the association between time from diagnosis to upfront surgery and survival in invasive breast cancer. METHODS: A systematic search of MEDLINE, Embase, CENTRAL, and additional sources was conducted through April 25, 2025. Quantitative studies in English or French assessing time to upfront surgery and prognosis were included; neoadjuvant cohorts were excluded. Two reviewers independently screened studies. Random-effects meta-analyses and meta-regression were performed. The primary outcome was overall survival; secondary outcomes included cancer-specific survival, recurrence, and pathologic upstaging. RESULTS: Twenty-six studies involving 4,921,120 patients were included. Compared with surgery within 30 days, delays of 30-59 days were associated with increased mortality (hazard ratio [HR] 1.08; p = 0.02), 60-89 days with a 12% higher risk (HR 1.12; p < 0.001), and 90-120 days with a 37% higher risk (HR 1.37; p = 0.002). Each additional 30-day delay increased mortality risk by 15% (HR 1.15; p < 0.001). Findings were robust after adjustment, with low publication bias. CONCLUSIONS: Delays as early as 30 days from diagnosis to upfront surgery are associated with progressively worse survival. Incorporating defined surgical timing benchmarks into clinical guidelines may improve quality of care and patient outcomes.
Hieken TJ, Flotte TJ, Zahrieh D
… +10 more, Johnson JE, Piltin MA, Tasche KK, Nelson GD, Strand CA, Jakub JW, Pirgousis P, Khariwala SS, Tuttle T, Block MS
Ann Surg Oncol
· 2026 Jun · PMID 42310271
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Kennedy ED, Simunovic M, Schmocker S
… +15 more, Pooni A, Brown CJ, MacLean AR, Liberman AS, Drolet S, Neumann K, Stotland P, Cho C, Kopek N, Burkes R, Jhaveri K, Pond GR, Kirsch R, Baxter NN, Rectal Cancer Alliance of Canada
Ann Surg Oncol
· 2026 Jun · PMID 42310267
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BACKGROUND: Patients with clinical Stage II or III rectal cancer routinely receive neoadjuvant radiotherapy and chemotherapy. But pelvic magnetic resonance imaging may identify patients who can safely avoid neoadjuvant t...BACKGROUND: Patients with clinical Stage II or III rectal cancer routinely receive neoadjuvant radiotherapy and chemotherapy. But pelvic magnetic resonance imaging may identify patients who can safely avoid neoadjuvant treatments. We evaluated 2-year oncologic outcomes for patients with "margin-clear" Stage II or III rectal cancer going directly to a planned low anterior resection. PATIENTS AND METHODS: This prospective, non-randomized, phase II trial was performed at 12 high-volume hospitals across Canada. Patients proceeded directly to a planned low anterior resection if they met the staging magnetic resonance imaging (MRI) criteria for "good prognosis" rectal cancer, including distance > 1 mm between primary tumor, tumor nodule, or positive mesorectal lymph node and the mesorectal fascia. Primary outcomes were 2-year rates of local recurrence, disease free survival, and overall survival. RESULTS: From 30 September 2014 to 31 December 2019, 139 patients met the inclusion criteria and were recruited for the study. Final pathology was Stage 1 in 59 (42%) patients and Stage II/III in 80 (58%). For the 80 Stage II or III patients, 2-year rates for local recurrence, disease free and overall survival were 1% (95% confidence interval [CI] 0-6.8), 85% (95% CI 75.3-92.0), and 99% (95% CI 93.2-100), respectively. Only 8% (6/80) (95% CI 2.8-15.6) received adjuvant radiotherapy. Preoperative staging MRI findings over-staged 30 of 59 pathology-confirmed Stage I patients (51%) (95% CI 37.5-64.1) to a clinical Stage II or III status. CONCLUSIONS: Among patients planned for a low anterior resection and with MRI criteria predicting margin-clear Stage II or III rectal cancer, a direct-to-surgery approach was associated with excellent 2-year oncologic outcomes and low use of radiation. TRIAL REGISTRATION: ISRCTN.com Identifier: ISRCTN05107772.
Tane S, Nomura K, Watanabe T
… +23 more, Takamori S, Ohara S, Oiki H, Katsumata S, Takamori S, Nakatsuka M, Tenpaku H, Nakamura R, Notsuda H, Namba K, Minegishi K, Kitamura Y, Abe M, Takegahara K, Konno H, Mizuno K, Toyoda T, Muto S, Toda M, Endo M, Maniwa Y, Soh J, Ohde Y
Ann Surg Oncol
· 2026 Jun · PMID 42310265
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BACKGROUND: While neoadjuvant immunochemotherapy has improved outcomes of resectable nonsmall cell lung cancer (NSCLC), treatment-induced tissue changes can increase surgical complexity. This study aimed to identify preo...BACKGROUND: While neoadjuvant immunochemotherapy has improved outcomes of resectable nonsmall cell lung cancer (NSCLC), treatment-induced tissue changes can increase surgical complexity. This study aimed to identify preoperative predictors of technically challenging surgery following neoadjuvant immunochemotherapy. PATIENTS AND METHODS: This multicenter retrospective analysis included 114 patients who underwent surgery after neoadjuvant nivolumab plus platinum-based chemotherapy at 29 institutions between March 2023 and July 2024. Challenging surgery was defined as one requiring bronchoplasty, pulmonary artery angioplasty, or pneumonectomy. Logistic regression was used to identify preoperative predictors for surgical complexity. RESULTS: Twenty-one patients (18.4%) required challenging surgeries, including bronchoplasty (n = 13), pulmonary artery angioplasty (n = 1), double-sleeve resection (n = 4), and pneumonectomy (n = 3). These cases had longer operative times (340 ± 118 vs. 267 ± 98 min, p < 0.001) and more frequently required open thoracotomy (90.5% vs. 44.1%, p < 0.001). Conventional predictive factors (T/N status, programmed cell death ligand expression, radiological response, and treatment-to-surgery interval) showed no association with surgical complexity. Post-treatment extranodal extension (ENE) after neoadjuvant therapy and before surgery was the strongest predictor of challenging surgery (univariable odds ratio [OR] 7.06, 95% confidence interval [CI]: 1.45-34.41, p = 0.009). Post-treatment ENE demonstrated a higher predictive accuracy for challenging surgery (positive predictive value [PPV] 50.0%) than that of pathological ENE metastasis (PPV 14.3%); thus, positivity reflects treatment-induced anatomical changes rather than residual tumor invasion. CONCLUSIONS: Unlike conventional predictors, post-treatment ENE may predict surgical complexity after neoadjuvant immunochemotherapy. ENE may be a potential marker of treatment-induced anatomical complexity rather than residual tumor burden, enabling evidence-based surgical planning in the immunotherapy era.
Sugase T, Kanemura T, Matsuura N
… +17 more, Yamamoto K, Ushimaru Y, Masuike Y, Yanagimoto Y, Yamamoto K, Sakano Y, Mori R, Kitakaze M, Kubo M, Fukuda Y, Komatsu H, Miyo M, Sueda T, Kagawa Y, Gotoh K, Kobayashi S, Miyata H
Ann Surg Oncol
· 2026 Jun · PMID 42307822
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Maekawa A, Perri G, Heo D
… +6 more, Cemin G, van Bodegraven AJ, De Nardi C, Grochowska A, Cillo U, Marchegiani G
Ann Surg Oncol
· 2026 Jun · PMID 42303818
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BACKGROUND: After curative-intent pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), disease recurrence occurs almost invariably. Evidence guiding treatment of recurrence remains limited and may differ across si...BACKGROUND: After curative-intent pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), disease recurrence occurs almost invariably. Evidence guiding treatment of recurrence remains limited and may differ across single-site recurrence patterns. METHODS: Scopus, MEDLINE, and the Cochrane Library were systematically searched for observational studies of adults with recurrent PDAC reporting liver-only, lung-only, or locoregional recurrence and post-recurrence treatments. Hazard ratio (HR) meta-analyses were performed to compare survival outcomes between treatment strategies for each recurrence location with additional descriptive survival summaries. RESULTS: The inclusion criteria were met by 22 studies, with 17 included in the quantitative synthesis. Pattern-specific analyses favored selected local therapies. For liver-only recurrence, local therapy was associated with longer overall survival than chemotherapy alone (HR 0.26, 95% confidence interval [CI] 0.14-0.49), mainly due to surgical resection (HR 0.18; 95% CI 0.11-0.31). Ablation did not reach statistical significance. In lung-only recurrence, surgical resection was associated with longer survival than conventional management (HR 0.35; 95% CI 0.26-0.48). For locoregional recurrence, resection was associated with longer survival (HR 0.52; 95% CI 0.38-0.72). Stereotactic body radiotherapy outcomes from three small series were summarized descriptively. CONCLUSIONS: Pancreatic ductal adenocarcinoma recurrence outcomes differ significantly by recurrence pattern. Across liver-only, lung-only, and locoregional recurrence, selected patients undergoing local therapy had longer survival than those managed conventionally. Although current observational data do not confirm broad efficacy for specific methods, these results support recurrence pattern-specific prospective evaluation to define optimal site-tailored strategies.
Goda T, Nakamura M, Hayata K
… +6 more, Kitadani J, Tominaga S, Fukuda N, Nakai T, Nagano S, Kawai M
Ann Surg Oncol
· 2026 Jun · PMID 42301592
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BACKGROUND: Esophageal cancer has a poor prognosis despite advances in multimodal treatment. Sarcopenia and low visceral adiposity have each been linked to adverse outcomes in some malignancies, but their combined impact...BACKGROUND: Esophageal cancer has a poor prognosis despite advances in multimodal treatment. Sarcopenia and low visceral adiposity have each been linked to adverse outcomes in some malignancies, but their combined impact on postoperative morbidity and survival after esophagectomy remains unclear. METHODS: We retrospectively analyzed 450 consecutive patients (2009-2019) who underwent curative esophagectomy. Preoperative computed tomography was used to assess the skeletal muscle mass index (SMI) and visceral adipose tissue index (VAI). Patients were classified according to sarcopenia status and low versus non-low VAI and stratified into groups: NN (normal SMI/normal VAI), NLA (normal SMI/low VAI), SN (low SMI [sarcopenia]/normal VAI), or SLA (low SMI [sarcopenia]/low VAI). Postoperative complications, overall survival, and disease-free survival were evaluated, with multivariate analyses identifying independent predictors. RESULTS: Postoperative complications occurred in 50.9% of patients and were more common in those with sarcopenia than in those without (p<0.0001), whereas low VAI alone was not associated with increased morbidity. Among the four groups, complication rates were highest in the SN and SLA groups (p=0.0002). Overall survival differed among the groups, with the poorest survival observed in the SLA group (p<0.0001). On multivariate analysis, SLA was an independent predictor of poorer overall survival (hazard ratio 1.851; 95% confidence interval 1.105-3.101, p=0.0193). Disease-free survival did not significantly differ among the groups. Non-cancer-related deaths were more common in the NLA, SN, and SLA groups than in the NN group. CONCLUSIONS: Sarcopenia combined with low visceral adiposity increases postoperative morbidity and worsens overall survival, driven mainly by non-cancer-related causes.