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Immune checkpoint inhibitors (ICIs) revolutionized the management of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal (GI) cancers. Based on notable results observed in the metastatic setting, several clinical trials investigated ICIs as neoadjuvant treatment (NAT) for localized dMMR/MSI-H GI cancers, achieving striking results in terms of clinical and pathological responses and creating the opportunity to spare patients from neoadjuvant chemotherapy and/or radiotherapy and even surgical resection. Nevertheless, these impressive findings are mainly derived from small proof of concept phase II studies and there are still several open questions to address. Moreover, dMMR/MSI-H represents a limited subgroup accounting for less than 10% of GI cancers. Consequently, many efforts have been produced to investigate neoadjuvant ICIs also in mismatch repair-proficient/microsatellite stable (MSS) cancers, considering the potential synergistic effect in combining immune-targeted agents with standard therapies such as chemo and/or radiotherapy. However, results for combining ICIs to the standard of care in the unselected population are still unsatisfactory, without improvements in event-free survival in esophago-gastric adenocarcinoma for the addition of pembrolizumab to chemotherapy, and sometimes limited benefit in patients with locally advanced rectal cancer. Therefore, a major challenge will be to identify among the heterogenous spectrum of this disease, those patients that could take advantage of neoadjuvant immunotherapy and deliver the most effective treatment. In this review we discuss the rationale of NAT in GI malignancies, summarize the available evidence regarding the completed trials that evaluated this treatment strategy in both MSI-H and MSS tumors. Finally, we discuss ongoing studies and future perspectives to render neoadjuvant immunotherapy another arrow in the quiver for the treatment of locally advanced GI tumors.
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http://dx.doi.org/10.1136/jitc-2023-008027 | DOI Listing |
Cancer Rep (Hoboken)
September 2025
Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan.
Background: Cancer of unknown primary (CUP) is a challenging malignancy characterized by metastatic tumors with an unidentified primary site, even after extensive pathological and radiographic evaluation. Recent advancements in gene expression profiling and comprehensive genomic profiling (CGP) using next-generation sequencing (NGS) have enabled the identification of potential tissue origins, thereby facilitating personalized treatment strategies. Although most cases of CUP present as adenocarcinomas or poorly differentiated tumors, the treatment remains largely empirical, with limited success from molecularly tailored therapies.
View Article and Find Full Text PDFKorean J Clin Oncol
August 2025
Division of Colon and Rectal Surgery, Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.
Purpose: This study aimed to analyze the benefit of neoadjuvant chemoradiation therapy (nCRT) versus adjuvant chemotherapy alone after surgery without nCRT on oncologic and perioperative outcomes of patients with extremely low rectal cancer requiring abdominoperineal resection (APR) when initially diagnosed.
Methods: Between March 2001 and December 2018, 88 patients who underwent APR for low rectal adenocarcinoma (anal verge < 4 cm) with clinical stage II and III (clinical T3/4, N -/+) were retrieved from a retrospective database. Sixty-eight patients received adjuvant chemotherapy alone after APR without nCRT, and 20 patients received nCRT before APR.
Eur J Surg Oncol
September 2025
Department of Surgical Sciences, Colorectal Surgery, Uppsala University, Uppsala University Hospital, Uppsala, 751 85, Sweden.
Background: Signet ring cell (SRC) colorectal cancer is strongly associated with peritoneal metastases (PM), but the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains uncertain due to poor prognosis. This study aimed to analyse the prognostic impact of SRCs, assess clinical characteristics, and evaluate the risk of open-close laparotomy.
Methods: This Swedish population-based study included patients with colorectal PM accepted for initial CRS and HIPEC at four national centres between 2010 and 2023.
Eur J Surg Oncol
September 2025
Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil. Electronic address:
Background: Ovarian cancer has the highest mortality among gynecologic malignancies. Despite cytoreductive surgery (CRS) and systemic therapy, peritoneal recurrence remains common. Hyperthermic intraperitoneal chemotherapy (HIPEC) delivers heated chemotherapy directly to the peritoneal cavity, enhancing local cytotoxicity and offering a potential therapeutic strategy.
View Article and Find Full Text PDFCancer Treat Res Commun
August 2025
Faculty of Medicine, American University of Beirut, 1107 Beirut, Lebanon; Department of Surgery, Division of General Surgery, American University of Beirut, 1107 Beirut, Lebanon. Electronic address:
Background: Neoadjuvant chemotherapy (NACT) is used to reduce breast cancer size before surgery, allowing for breast conservation surgery (BCS) instead of mastectomy. However, concerns exist about higher positive margins and local recurrence rates.
Aims: This study compared the incidence of positive margins, local recurrence rates, and other oncologic outcomes of BCS performed either upfront or after NACT.