Abstract Backgrounds: BRAF genomic alterations (GAs) have been identified in various tumors and are categorized into three distinct classes. Based on their impact on RAS-independent kinase activity, class 1 (monomer) and class 2 (dimer) are significant treatment targets and class specific regimens are being developed. However, the distribution of these classes across different primary sites has not yet been clarified. In patients with pancreatic cancer (PC), class 2 BRAF GAs have occasionally been encountered in clinical practice. Because precision oncology is limited in PC, BRAF GAs are precious target. To elucidate the patterns of BRAF GAs in PC, we investigated two extensive databases. Methods: We analyzed the Japanese nationwide C-CAT data and the AACR Project GENIE data. BRAF GAs were annotated using OncoKB and AlphaMissense and classified into three classes based on the published literature. Results: In the C-CAT data (N=107,714), as summarized in the table, BRAF GAs (n=3559, 3.3%) were frequently observed in thyroid, skin, and colorectal cancers, but these were mainly class 1(mostly V600E). In contrast, PC showed a distinct profile: among 11,959 patients with PC, BRAF GAs were detected in 230 (1.92%), Class1 was relatively rare (15.6%) and 60.4% (139/230) were class 2. These were mainly composed of in-frame deletions (n=97), with N486_P490del (n=79) and fusions (n=28). In GENIE data (N=250,018), 1.6% (169/10,730) of patients with PC harbored BRAF GAs. Although proportion of V600E was higher than that in C-CAT (19.5%), class 2 was dominant (63%, 108/169), such as fusions(n=48) and N486_P490del (n=28). Among BRAF N486_P490del positive solid tumors, pancreas was dominant primary site in both C-CAT (82%, 79/96) and GENIE (52%, 28/53). Conclusions: Class 2 BRAF GAs, especially N486_P490del and fusions, are distinctive alterations in patients with PC, and the development of class 2 specific targeted therapies is urgently needed. Citation Format: Kiyoaki Ochi, Chigusa Morizane, Kouya Shiraishi, Takafumi Koyama, Kuniko Sunami, Rui Kitadai, Yusuke Okuma, Tetsuro Shiraishi, Eiichiro So, Yuno Goto, Shiho Hakui, Keita Fujisaki, Kazunori Onuma, Yasuhiro Komori, Daiki Yamashige, Mao Okada, Shota Harai, Yuta Maruki, Yasuyuki Kawamoto, Yoshikuni Nagashio, Susumu Hijioka, Hideki Ueno, Takushi Okusaka. BRAF N486_P490del and fusions as distinctive gene alterations in pancreatic ductal adenocarcinomas: Analysis of C-CAT and AACR Project GENIE data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3991.

The oncologic outcomes of pedunculated-type T1 colorectal cancer (CRC) remain unknown. We determined the risk factors for lymph node metastasis (LNM) and recurrence and evaluated the survival according to the treatment method. In this multicenter retrospective study involving 4673 patients with T1 CRC, we analyzed 444 patients with pedunculated-type T1 CRC treated between 2009 and 2016. Treatment included local resection (LR) alone (n = 169), surgery with lymph node (LN) dissection alone (n = 83), and LR followed by additional surgery with LN dissection (n = 192). Factors associated with LNM and recurrence, relapse-free survival (RFS) and overall survival (OS) by treatment were analyzed. The median follow-up period was 64 months. LNM and recurrence were observed in 25 (5.6

LBA3508 Background: Observational studies suggest aspirin benefits in colorectal cancer (CRC), but adjuvant evidence remains limited. In unselected populations, phase III trials have not shown a clear benefit, while biomarker-selected studies suggest a benefit in PI3K-altered tumors. EPISODE-III evaluates whether low-dose aspirin improves disease-free survival (DFS) in unselected stage III CRC receiving standard adjuvant chemotherapy. Methods: EPISODE-III is a multi-institutional, two-arm, randomized, double-blind, placebo-controlled phase III trial at 36 institutions in Japan. Eligible patients (20–80 years; ECOG PS 0–1) with histologically confirmed, R0-resected stage III adenocarcinoma from the cecum to upper rectum (lower rectum excluded) after D2/D3 lymph node dissection were randomized 1:1 to low-dose aspirin (100 mg once daily) or matched placebo for 3 years, in addition to standard adjuvant chemotherapy (capecitabine, mFOLFOX6, or CAPOX). Randomization was balanced by institution, sex, stage (IIIA/IIIB/IIIC), and planned oxaliplatin use. The primary endpoint was DFS (event: relapse, second cancer, or death). Secondary endpoints included overall survival (OS), relapse-free survival (RFS), relative dose intensity (RDI) of aspirin and placebo, and safety. The planned sample size was 880 (279 DFS events), providing 80% power with a one-sided α = 0.05 to detect hazard ratio (HR) of 0.741 (assumed 3-year DFS 74% vs. 80%). Results: Between Mar 2018 and Oct 2022, 882 patients (placebo 442; aspirin 440) were enrolled. At the data cutoff (Oct 2025), the median follow-up for all randomized patients was 4.0 years, with 231 DFS events (placebo 124; aspirin 107). Baseline characteristics were balanced (median age 65 vs. 64 years; pIIIA/IIIB/IIIC 19/63/18% vs. 19/62/19%; planned oxaliplatin-containing regimen 70% vs. 71%). Three-year DFS was 75.4% with placebo and 78.8% with aspirin (+3.4%); the primary endpoint was not met (HR 0.84, 95% CI 0.65–1.09; one-sided p=0.0987). DFS, RFS, and OS are shown in the Table. Grade ≥3 adverse events were similar between arms, and grade ≥3 aspirin-related adverse events were <1% (lower GI bleeding n=4). One treatment-related death was observed in the aspirin arm during chemotherapy (ischemic heart disease). RDI was high and comparable (median 98.6% in both arms). Conclusion: Low-dose aspirin added to standard adjuvant chemotherapy did not significantly improve DFS in unselected stage III CRC. However, a numerical DFS improvement with good tolerability was observed. Exploratory biomarker analyses including PI3K/PIK3CA are ongoing and will inform a planned collaborative meta-analysis of randomized trials. Clinical trial information: jRCTs031180009. 3-year (%)placebo vs. aspirin HR (95% CI) P (one-sided) DFS 75.4 vs. 78.8 0.84 (0.65–1.09) 0.0987 RFS 77.2 vs. 79.5 0.87 (0.66–1.14) - OS 96.6 vs. 95.2 1.02 (0.65–1.60) -

We report a rare case of giant hepatocellular carcinoma (HCC) with direct invasion to the colon and synchronous multiple lung metastases that achieved complete remission with surgical hepatectomy followed by chemotherapy with atezolizumab and bevacizumab. An 80-year-old man presented with abdominal distension and appetite loss. Imaging studies demonstrated a large HCC protruding from the liver with compression and invasion of the ascending colon, accompanied by multiple bilateral pulmonary nodules. To relieve symptoms and reduce the risk of tumor rupture, upfront surgical resection consisting of right hepatectomy and right hemicolectomy was performed. Histopathological examination revealed moderately to poorly differentiated HCC with direct invasion into the ascending colon and microscopic portal vein invasion. Postoperatively, tumor markers initially decreased; however, subsequent elevation led to initiation of atezolizumab plus bevacizumab for treatment of pulmonary metastases. Tumor markers subsequently normalized, and follow-up computed tomography demonstrated disappearance of all pulmonary metastases, with only scar-like lesions remaining. Radiologic complete remission was achieved 14 months after hepatectomy. The patient remains alive without recurrence 54 months after surgery. Direct invasion of HCC into adjacent organs is extremely rare and is generally associated with poor prognosis. The role of systemic chemotherapy after reduction surgery for advanced HCC remains controversial. Although this is a single case experience and caution is needed when generalizing, this case suggested that combined treatment with initial resection of the primary tumor followed by immunotherapy for remnant lesions could be feasible in selected patients and would potentially contribute to symptom relief and control of metastatic lesions.

INTRODUCTION: Bacterial translocation (BT) followed by bacteremia is usually managed with antibiotics, but some cases remain refractory. Herein, we report an immunocompromised patient with bacteremia due to the translocation of Enterococcus gallinarum, a rare pathogen among enterococcal infections, who was successfully treated with surgical intervention. CASE PRESENTATION: A 69-year-old woman with prior low anterior resection for rectal cancer developed adhesive intestinal obstruction during steroid treatment for suspected pyoderma gangrenosum. She progressed to septic shock despite antibiotics. CT revealed an edematous, thickened colon, suggesting ischemia or necrotizing colitis. An urgent laparotomy revealed no necrosis. The markedly edematous right colon was resected, with the creation of an ileostomy and a mucous fistula. Blood and colonic wall cultures both yielded Enterococcus gallinarum, confirming BT sepsis. Intravenous levofloxacin and selective digestive decontamination from the mucous fistula achieved recovery. Stoma closure was performed 6 months later without recurrence of bacteremia. CONCLUSIONS: Intestinal resection serving as the portal of entry for BT should be considered in patients unresponsive to conservative management.

BACKGROUND:Early adoption of new surgical technologies represents a critical period for acquiring operative experience that may influence surgeons' careers. However, whether access to operative opportunities during the introduction of robot-assisted surgery differs according to the surgeon's sex remains unclear. METHODS:This retrospective observational study used data from the National Clinical Database, a multicenter database covering more than 95% of all surgeries in Japan. Male and female gastroenterological surgeons who performed distal gastrectomy or low anterior resection between January 1, 2023 and December 31, 2024 were included. The primary outcome was the number of operations performed per surgeon, stratified by sex and years since medical registration. RESULTS:A total of 47,934 distal gastrectomies and 38,230 low anterior resections were included in the analysis. For both procedures, the proportion of operations performed by female surgeons was lowest for robot-assisted surgery. For distal gastrectomy, the proportions were 4.32%, 9.47%, and 11.86% and for low anterior resection, 5.41%, 8.41%, and 8.57% (robot-assisted, laparoscopic, and open, respectively). For robot-assisted procedures, the number of operations performed per surgeon increased with years since medical registration among male surgeons, whereas no comparable increase was observed among female surgeons. Sex differences became apparent at approximately 10 years after medical registration. CONCLUSION:Substantial sex-based disparities in operative opportunities were observed during the early adoption phase of robot-assisted surgery. These disparities were most pronounced for robot-assisted procedures compared with laparoscopic and open surgery. Inequities in access to newly introduced surgical technologies may contribute to persistent sex disparities in surgical careers.

Numbers of patients undergoing hepato-biliary-pancreatic (HPB) surgery are increasing worldwide. However, elderly patients may experience loss of independence (LOI) postoperatively due to the marked invasiveness of surgical procedures. This retrospective cohort study aimed to investigate clinical characteristics of elderly patients including preoperative low skeletal muscle mass before HPB open surgery for malignancy, and the association between low skeletal muscle mass and LOI postoperatively. Patients aged 65 or older who underwent open curative resection for HPB malignancies in our institution between September 2021 and October 2024 were selected. Skeletal muscle index was measured preoperatively using bioelectrical impedance analysis. Characteristics of patients with low muscle mass (< 7.0 kg/m² for males or < 5.8 kg/m² for females) and risk factors for LOI were evaluated retrospectively. Of 148 eligible patients, 15 (10.1

Long-term follow-up after groin hernia repair is inherently challenging, and procedure-based registries do not directly capture true recurrence rates. Using the hernia-specific data collection of the National Clinical Database (NCD), which records detailed information at the time of surgery for recurrence, this study aimed to clarify the timing and hernia types of surgically treated recurrent groin hernias, including very long-term reoperations following childhood repair. Recurrence-related analyses were conducted using the hernia-specific data collection of the NCD. The analyses focused on annual surgical volumes of primary and recurrent groin hernia repair, the timing of reoperation and hernia type at reoperation among recurrent cases, and a predefined subanalysis of very long-term reoperations following childhood hernia repair. Recurrent surgeries accounted for 3.6–3.8

To investigate whether colorectal cancer (CRC) sidedness is associated with intraoperative lavage cytology results, tumor recurrence, and prognosis. Using data from a multicenter prospective observational study conducted by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), we retrospectively analyzed prognosis and recurrence patterns in pathological stage II/III right-sided and left-sided CRC, stratified by positive versus negative lavage cytology results. A total of 1500 patients met the inclusion criteria and were enrolled. Of these, 534 had right-sided CRC and 966 had left-sided CRC. Fifty-nine patients (3.9

To evaluate contemporary short-term outcomes of robotic gastrectomy (RG) approximately 5 years after its widespread implementation, compared with laparoscopic gastrectomy (LG) using a nationwide Japanese database. RG has been introduced to overcome the technical limitations of LG; however, its real-world clinical advantages remain to be fully defined. This retrospective study used the Japanese National Clinical Database to identify patients with gastric cancer who underwent minimally invasive distal gastrectomy (DG) or total gastrectomy (TG) between January 2023 and December 2024. Patients were classified as undergoing robotic (RDG or RTG) or laparoscopic (LDG or LTG) procedures. Propensity score matching was performed separately for the DG and TG cohorts to adjust for patient-, tumor-, and hospital-related confounders. The primary outcome was postoperative morbidity within 30 days (Clavien–Dindo grade ≥ IIIa). After propensity score matching, 9743 RDG–LDG pairs and 1617 RTG–LTG pairs were analyzed. RDG was associated with a significantly lower morbidity rate than LDG (4.3 vs. 4.9

Neoadjuvant chemotherapy with 5-FU, cisplatin, and docetaxel (DCF) is standard for resectable esophageal cancer in Japan but is linked to severe adverse events. We report three cases of esophagorespiratory fistulas (ERFs) occurring during DCF therapy. Case 1: A 72-year-old woman (cStage II) developed fever after two DCF cycles. CT and esophagography confirmed an ERF. An esophageal stent was placed, but she later opted for best supportive care. Case 2: A 53-year-old man (cStage IIIB) developed pneumatosis intestinalis and pneumonia nine days into DCF. Imaging confirmed an ERF. He received a stent on day 19 and continued chemotherapy for over a year. Case 3: A 65-year-old man (cStage IIIA) presented with dyspnea eight days after starting DCF. CT revealed pneumothorax and pyothorax. A stent was placed on day 19. His condition initially improved but later declined, leading to best supportive care. DCF therapy may enhance survival but carries significant risk for ERFs. Early recognition of symptoms and rapid intervention are critical to managing complications.

Tumor size plays a central role in the staging, resectability assessment, and response evaluation of pancreatic ductal adenocarcinoma (PDAC). However, radiologic tumor size does not necessarily correspond to pathologic tumor size, and this discrepancy has become more clinically relevant in the preoperative therapy era. PDAC is characterized by infiltrative growth, abundant desmoplastic stroma, and ill-defined tumor borders, all of which complicate accurate size assessment on imaging. After preoperative therapy, fibrosis, necrosis, and scattered residual tumor cells further obscure the relationship between radiologic abnormalities and viable tumor burden. This review summarizes the mechanisms underlying radiologic–pathologic discrepancies in tumor size assessment of PDAC, with a focus on computed tomography, magnetic resonance imaging, ultrasound, and pathologic evaluation after preoperative therapy. We also discuss the prognostic implications of imaging-based and pathological tumor sizes and highlight the limitations of size-based response assessment. Finally, we review emerging approaches beyond conventional size metrics, including functional imaging, radiomics, and pathological standardization. Recognizing the biological and treatment-related basis of tumor size discrepancy is essential for improving tumor assessment and refining staging strategies in contemporary PDAC management.

BACKGROUND AND AIMS:Chronic background mucosal inflammation contributes to colorectal cancer (CRC) development in ulcerative colitis (UC), but its prognostic impact is unclear. We evaluated whether background mucosal inflammation documented at cancer diagnosis is associated with oncologic outcomes. METHODS:This retrospective study analyzed 1189 UC patients diagnosed with CRC using a nationwide, multicenter database in Japan. Patients were classified as CRC within the UC-involved area (within-area) or outside the UC-involved area (outside-area), based on tumor location relative to the UC disease extent documented endoscopically at cancer diagnosis. The primary end point was 5-year recurrence-free survival (RFS), and the secondary end point was 5-year cancer-specific survival (CSS). In within-area cases, inflammation severity was assessed using the Mayo Endoscopic Score (MES), stratified as Inactive, Mild-Moderate, and Severe. RESULTS:Of the 723 eligible patients, 683 had within-area and 40 outside-area CRC. Five-year RFS was significantly lower in within-area than outside-area CRCs (75.1% vs 87.6%, P = 0.022). Multivariable Cox regression analysis of RFS revealed this classification as an independent prognostic factor (hazard ratio = 2.99, 95% confidence interval: 1.09-8.18, P = 0.030). A significant difference was also observed in 5-year CSS (P = 0.038). Among within-area cases, higher MES was associated with stepwise declines in RFS (P = 0.150), and a similar, statistically significant gradient in CSS (P = 0.048). CONCLUSIONS:Background mucosal inflammation at cancer diagnosis is associated with significantly worse prognosis of CRC in UC patients. Systematic endoscopic assessment at cancer diagnosis may aid prognostic stratification and inform management.

691 Background: Being familial pancreatic cancer (FPC) is defined as a family in which at least two first-degree relatives have pancreatic cancer (PC). The previous study has shown that being an FPC patient is poor prognostic indicator for PC patients who undergo resection and receive adjuvant chemotherapy. However, the impact of FPC on the prognosis remains unclarified because the cohort was small and from single institutional report. Methods: This multi-center, retrospective cohort study collected the data on FPC patients who were introduced postoperative adjuvant chemotherapy without neoadjuvant chemotherapy (NAC) between January 2013 and December 2019 from 27 facilities in Japan. Among 27 facilities, data on non-familial pancreatic cancer (Non-FPC) patients serving as controls were collected from nine institutions where family history interviews were conducted in two or more departments, in order to prevent the mixing of data on FPC due to insufficient interviews. The primary endpoint was recurrence-free survival (RFS) in the study. The potential 10 confounders including preoperative and pre-adjuvant treatment induction CA19-9 levels were selected based on clinical relevance. To estimate the treatment effect of FPC, a Cox proportional hazards model was applied with adjustment for these confounders. The hazard ratio (HR) was used as the primary measure of treatment effect. Median RFS were estimated by the Kaplan-Meier method. Results: The study included 620 patients (FPC = 157; Non-FPC = 463). In the FPC group, S-1 was administered as adjuvant chemotherapy in 151 patients (96%), GEM in five patients (3%), and other in one patient (1%). The ratio of selected adjuvant chemotherapy regimens was almost the same for the Non-FPC group (P=0.665). Median CA19-9 levels before surgical resection and adjuvant chemotherapy were statistically, but not numerically different between FPC and non-FPC groups (56 vs. 54 U/mL with p = 0.005 and 13 vs. 14.1 U/mL with 0.010, respectively. Median RFS was 21.7 months in the FPC group and 25.6 months in the Non-FPC group. Among patients who received postoperative adjuvant chemotherapy without neoadjuvant chemotherapy, FPC was an independent indicator for poor RFS (Hazard ratio, 1.26; 95% Confidence interval, 1.00–1.58; P=0.049). Conclusions: The present study validated that FPC patients had a worse RFS than Non-FPC patients from multi-center, retrospective cohort study. These results suggest that different treatment strategy is needed to improve the prognosis of FPC patients.

For patients with left-sided metastatic colorectal cancer (mCRC), the recommended first-line treatment is anti-epidermal growth factor receptor (anti-EGFR) antibodies, such as cetuximab or panitumumab, plus doublet chemotherapy. However, the differences in outcomes between cetuximab and panitumumab remain unknown. Clinical data of patients with left-sided all RAS or KRAS wild-type mCRC who received cetuximab or panitumumab plus doublet chemotherapy were retrospectively collected from 24 institutions in Japan. The patients were divided into two groups: the cetuximab and panitumumab groups. Overall survival (OS), progression-free survival (PFS), and response rate (RR) were compared between the two groups. A total of 233 patients were enrolled: 87 (37.3

Polyploid giant cancer cells (PGCCs) are characterized by abnormal enlargement and considerable polyploidy. Though the presence of giant cancer cells has been documented for decades, they remain not fully understood, especially in clinical practice, due to diagnostic challenges, and confusion regarding synonyms for PGCCs still exists. Thus, understanding PGCCs may be a key clue to overcoming them. This review offers a comprehensive overview of PGCCs, integrating insights from basic research and clinical studies to enhance understanding of their complex biology and clinical implications. In basic research, PGCCs are known to emerge under various stressors, including chemotherapy exposure, radiation, viral infection, and hypoxic environments. These cells play crucial roles in tumor progression through multiple mechanisms: enhancing genetic diversity, and facilitating metastatic spread via asymmetric cell division and genomic instability. In clinical studies, PGCC-containing tumors have been shown to exhibit marked treatment resistance and are associated with a poor prognosis across multiple solid tumor types, including prostate, lung, and pancreatic cancers. Despite these therapeutic challenges, paclitaxel-containing regimens have shown promising results in PGCC-containing tumors, such as pleomorphic carcinoma of the lung and undifferentiated carcinoma of the pancreas. Furthermore, emerging targeted therapies directed at specific pathways in PGCCs, particularly those involving TP53, represent potential strategies to improve clinical outcomes of patients with PGCC-containing tumors.

Pyloromyotomy is a technique for relieving infantile hypertrophic pyloric stenosis and is performed almost safely without severe complications during long-term outcomes. To the best of our knowledge, this is the first reported case of pancreatic cancer arising from the pancreatic parenchyma embedded within the pyloric ring after neonatal pyloromyotomy. A 39-year-old woman with a history of infantile hypertrophic pyloric stenosis underwent a pyloromyotomy during the neonatal period and presented with progressive nausea and vomiting. Imaging studies suggested the presence of ectopic pancreatic or gastric cancer invading the pancreas. After laparotomy, tumor invasion of the pancreatic head was identified; therefore, pancreaticoduodenectomy was performed. Pathological examination confirmed pancreatic cancer arising from the pancreatic parenchyma embedded within the duodenal and pyloric muscle layers. The patient completed 6 months of adjuvant chemotherapy with oral S-1. Peritoneal dissemination was observed 23 months postoperatively. Abnormal embedding of the pancreatic head in the walls of the duodenum and pyloric ring was considered to be related to neonatal pyloromyotomy. This alteration requires careful preoperative evaluation and flexible surgical planning to achieve curative resection of atypical presentations of gastrointestinal malignancies. The cancer in the present case may be associated with long-term anatomical alterations following neonatal pyloromyotomy, although a direct causal relationship cannot be established.

ABSTRACT Aims To explore the therapeutic impact of D3 lymph node dissection for non‐metastatic colon cancers, evaluating the therapeutic value index for each lymph node station according to surgical stages. Methods Consecutive patients with surgical Stage I–III colon and rectosigmoid cancer who underwent curative resection between January 2003 and December 2014 were identified from the Japanese Society for Cancer of the Colon and Rectum database and analyzed. The therapeutic value index (TVI) was defined as the incidence of lymph node metastasis times 5‐year overall survival and calculated for each nodal station stratified by tumor stages. Results A total of 21 914 patients, including 9583 patients with right‐sided colon cancer and 12 331 with left‐sided colon cancer, were eligible for analysis. In right‐sided colon cancer, reflecting differences in tumor location and the presence of the right colic artery, variability in the TVIs was observed among stations #203 to #223. When the three stations were collectively considered as a single group of main lymph nodes, the combined TVIs for sT1Nany, sT2N0, sT2Nany, sT3‐4 N0, and sT3‐4Nany were 0.630, 0.493, 0.857, 0.849, and 2.274, respectively. For station #253 in left‐sided colon cancers, the TVIs for sT1Nany, sT2N0, sT2Nany, sT3‐4 N0, and sT3‐4Nany were 0.120, 0.278, 0.634, 0.475, and 1.234, respectively. Conclusion Within a D3‐treated cohort stratified by surgical stage, the TVI of the main lymph nodes for sT2N0 tumors remained low, approximating that of sT1Nany rather than sT2Nany or sT3‐4 tumors. Further evaluation of the therapeutic impact of D3 lymphadenectomy for clinically node‐negative T2 colon cancer is warranted.

Objective:This randomized phase II/III study evaluated the superiority of neoadjuvant therapy with gemcitabine plus S-1 over upfront surgery for patients with resectable pancreatic ductal adenocarcinoma (PDAC).Background:PDAC is a leading cause of cancer mortality that urgently requires better treatment.Methods:Patients with resectable PDAC (without arterial abutment) were randomly assigned to upfront surgery or neoadjuvant chemotherapy with gemcitabine (1000 mg/m2 days 1 and 8) and S-1 (40-60 mg orally twice daily, days 1-14 every 3 wk for 2 cycles). Phase II and III primary endpoints were resection rate and overall survival, respectively. UMIN Clinical Trials Registry number: UMIN000009634.Results:Patients (n=364) were enrolled and randomly allocated to upfront surgery (UPS; n=182) or neoadjuvant gemcitabine plus S-1 (NAC-GS; n=182). Patient demographics and tumor characteristics were balanced between groups. Median overall survival in the UPS and NAC-GS groups was 26.6 (95% CI: 21.5, 31.5) and 37.0 (95% CI: 28.6, 43.3) months, respectively. The hazard ratio for mortality in the NAC-GS group compared with the UPS group was 0.73 (95% CI: 0.56, 0.95; P=0.018). Median relapse-free survival in the UPS and NAC-GS groups was 11.3 (95% CI: 9.41, 13.5) and 14.3 (95% CI: 11.7, 17.0) months, respectively. The hazard ratio for relapse in the NAC-GS group compared with the UPS group was 0.77 (95% CI: 0.61, 0.98; P=0.030).Conclusions:The Prep-02/JSAP05 trial results showed that neoadjuvant chemotherapy with gemcitabine plus S-1 significantly extends survival compared with upfront surgery in patients with resectable PDAC.