The number of deaths from colorectal cancer in Japan continues to rise, with over 50,000 deaths recorded in 2018. In the 2024 edition, revisions to all aspects of treatment were undertaken, with corrections and additions made based on knowledge gained since the 2022 version (drug therapy) and the 2019 version (other treatments). The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2024 for the treatment of colorectal cancer have been prepared to present standard treatment strategies, reduce disparities among institutions, avoid both unnecessary and insufficient treatment, and enhance mutual understanding between healthcare professionals and patients by making these guidelines accessible to the public. These guidelines were developed through consensus by the JSCCR Guideline Committee, following a careful review of evidence retrieved from literature searches and considering the medical insurance system and actual clinical practice in Japan. Therefore, these guidelines serve as a tool for managing colorectal cancer in real-world clinical settings. More specifically, they can be used to support obtaining informed consent from patients and selecting the most appropriate treatment method for each patient. Controversial topics were selected as clinical questions, and recommendations were provided. Each recommendation is accompanied by an evidence classification and a recommendation category, both based on consensus reached by the Guideline Committee members. This article presents the English version of the JSCCR guidelines 2024.

Purpose: Posttreatment detection of ctDNA is strongly predictive of recurrence. Most minimal/molecular residual disease assays require prior tissue testing to guide ctDNA analysis, resulting in lengthy time to initial results and unevaluable patients. Experimental Design: We assessed a tissue-free assay (Guardant Reveal) that bioinformatically evaluates >20,000 epigenomic regions for ctDNA detection in 1,977 longitudinally collected postoperative plasma samples from 342 patients with resected colorectal cancer. Results: We observed sensitive and specific detection of minimal/molecular residual disease associated with clinically meaningful differences in recurrence-free intervals at each time point evaluated with a median lead time of 5.3 months. The longitudinal sensitivity in stage II or higher colon cancer was 81%. Sensitivity increased with serial measurement and varied by recurrence site: higher for liver (100%) versus lung (53%) and peritoneal (40%). Sensitivity among patients with rectal cancer was 60% owing to a high proportion of lung metastases. Specificity was 98.2% among 1,461 posttreatment samples (99.1% among those with follow-up longer than the upper IQR of the lead time observed in this study). Conclusions: Our data demonstrate the potential clinical utility of ctDNA as a tool to improve the management of stage II and higher colorectal cancer with a methodology that is noninvasive, accessible, and allows for rapid evaluation to inform clinical decisions.

PURPOSE: The phase III ACHIEVE trial conducted in Japan was one of six prospective studies included in the International Duration Evaluation of Adjuvant Therapy collaboration, which explored whether 3 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) therapy would be noninferior to 6 months of treatment in patients with curatively resected stage III colon cancer. We report the final analyses of survival and long-term safety. PATIENTS AND METHODS: Eligible patients were randomly assigned (1:1) to either 3 or 6 months of adjuvant chemotherapy (modified [m]FOLFOX6 or CAPOX, as selected by the treating physician). Random assignment was stratified according to number of involved lymph nodes, center, regimen, primary site, and age. The primary end point was disease-free survival, assessed in the modified intention-to-treat population. Overall survival (OS) was a secondary end point. RESULTS: The modified intention-to-treat population comprised 1,291 patients: 641 in the 6-month treatment group and 650 in the 3-month treatment group. Median follow-up for this analysis was 74.7 months. Five-year OS rates were comparable: 87.0% in the 3-month treatment group and 86.4% in the 6-month treatment group (hazard ratio, 0.91; 95% CI, 0.69 to 1.20; P = .51). Subgroup analysis of OS did not reveal a significant interaction between baseline characteristics and treatment duration. Peripheral sensory neuropathy lasting longer than 5 years was more common in the 6- compared with 3-month treatment group (16% v 8%, respectively), and in those receiving mFOLFOX6 compared with CAPOX (14% v 11%, respectively). CONCLUSION: In Asian patients, shortening adjuvant therapy duration from 6 to 3 months did not compromise efficacy and reduced the rate of long-lasting peripheral sensory neuropathy. In this setting, 3 months of CAPOX therapy is an appropriate adjuvant treatment option.

Overall survival remains unsatisfactory in stage II/III gastric cancer, even after curative surgery and adjuvant chemotherapy. Platelet-derived growth factor receptor-β (PDGFR-β) is associated with the proliferation of cancer cells. The present study therefore investigated the association of PDGFR-β gene expression with patient outcome in 134 stage II/III gastric cancer patients who received adjuvant chemotherapy with S-1. Relative PDGFR-β gene expression was measured in surgical cancer tissue and adjacent normal mucosa specimens by reverse transcription-quantitative polymerase chain reaction. The PDGFR-β gene expression levels were found to be significantly higher in the cancer tissues compared with the adjacent normal mucosa. A high level of PDGFR-β gene expression was associated with a significantly poorer 5-year overall survival rate compared with a low level of PDGFR-β expression. Upon multivariate analysis, PDGFR-β gene expression was found to be an independent predictor of survival. Overall, the study indicates that PDGFR-β overexpression in gastric cancer tissues is a useful independent predictor of outcome in patients with stage II/III gastric cancer who receive adjuvant chemotherapy with S-1.

Objective: To investigate the incidence of male sexual dysfunction including erectile dysfunction (ErD) and ejaculatory dysfunction (EjD) after minimally invasive rectal cancer surgery. Background: Male sexual dysfunction significantly affects after rectal cancer surgery quality of life. Current assessments using the International Index of Erectile Function-5 are unsuitable for patients with reduced postoperative sexual activity because it assume sexual intercourse. This study addresses this gap using the Erection Hardness Score and custom ejaculatory questionnaires. Methods: This prospective multicenter open-label phase 2 trial enrolled 399 patients who underwent laparoscopic (Lap), robotic (Ro), or transanal (Ta) rectal cancer surgery. Erection Hardness Score and custom ejaculatory questionnaires assessed ErD, EjD, and potency impairment at 3, 6, and 12 months postoperatively. The rates were assessed in the full analysis set and compared between the Lap and Ro groups after propensity score matching. Results: At 12 months, the overall incidences of ErD and EjD were 34.7% and 29.8%, respectively. The Ro group showed a significantly lower EjD rate (25.0%) than the Lap group (40.9%), with no significant difference in ErD. Potency impairment was lower in the Ro group at 6 months (32.7% vs 22.3%) and 12 months (29.0% vs 17.8%) postoperatively. The Ta group showed relatively high ErD and EjD at 3 months, with some recovery at 12 months. Conclusions: Minimally invasive rectal cancer surgery commonly results in ErD, EjD, and potency impairment. Ro surgery provides lower EjD rates and less potency impairment. Comprehensive sexual function assessments are essential to inform patients and improve quality of life outcomes.

Background/Objectives: BRAF mutations occur in 5–10% of metastatic colorectal cancer (mCRC) cases, but their implications for prognosis and optimal treatment remain unclear. Methods: This multicenter, prospective observational study analyzed 377 RAS wild-type cases from 511 patients across 32 centers, using PCR-based methods. Results: BRAF mutations were identified in 21% (79/377) of cases, predominantly V600E (89.9%) with a minority of non-V600E (10.1%). Microsatellite instability (MSI) testing revealed MSI-high in 11.3%, exclusively among V600E cases. V600E mutations were linked to right-sided tumors, poor differentiation, and elevated CA19-9 levels. Median survival was significantly lower in V600E cases compared to BRAF wild-type (12.4 vs. 37.5 months, HR 3.25, p < 0.001) and marginally lower non-V600E cases (12.4 vs. 34.7 months, HR 0.61, p = 0.057). Chemotherapy regimens (doublet vs. triplet) and targeted treatments (bevacizumab vs. anti-EGFR) showed no significant survival differences in V600E patients. Similarly, RAS/BRAF wild-type patients had comparable survival with bevacizumab versus anti-EGFR, even for left-sided tumors. Conclusions: These findings highlight distinct clinical and prognostic profiles for BRAF V600E and non-V600E mutations, while treatment choice appears to have limited impact on survival in these subgroups or RAS/BRAF wild-type cases.