2026-07-07 | Knowledge gaps in tubular gut tumours: a critical appraisal of the 6th edition of the World Health Organization classification of tumours.
Gastrointestinal cancer is a global health problem. In the new 6th edition of the World Health Organization Classification of Tumours (WCT) of the Digestive System, updated evidence and guidance is provided for the aetiology, pathogenesis, diagnosis, classification, grading, staging and prognosis of these tumours. However, significant knowledge gaps remain, some of which are addressed in this review. To provide for a research framework to fill these knowledge gaps, we focused on precursor lesions and rare cancers, where the need for new evidence is most urgent. Areas with a need for further research are discussed for neoplastic precursors of the oesophagus (squamous epithelium), stomach (gastric dysplasia and adenomas), ampulla-duodenum, jejunoileum, anal canal, as well as for colorectal serrated polyposis and inflammatory bowel disease associated dysplasia (conventional and non-conventional). Knowledge gaps are also presented as they exist in rare cancers of the oesophagus (mixed type), appendix (mucinous neoplasms and mucinous adenomas), colorectum (three new subtypes) and anus, as well as for neuroendocrine tumours (grading, necrosis and two new gastric subtypes) and undifferentiated carcinomas (deficiencies of the SWI/SNF chromatin remodelling complex and mesenchymal differentiation). We identify and present research questions and persistent challenges for these entities and thus propose research frameworks that focus on specific priority areas. Progress in these core research topics for both neoplastic precursors and rare cancers will hopefully be reflected in future editions of the WCT, but many of these knowledge gaps will only be resolved with collective registries and collaborative research efforts. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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2026-05-29 | Updates on Management of Anal Cancer: A New Era Has Begun.
Squamous cell carcinoma of the anal canal (SCAC) is a rare, human papillomavirus-driven malignancy with a rising global incidence and an increasingly dynamic therapeutic landscape. This review summarizes recent advances and current evidence in the management of SCAC, with a focus on immunotherapy, systemic treatment strategies, and optimization of curative-intent approaches. For locally advanced SCAC, concurrent chemoradiotherapy with fluorouracil and mitomycin C remains the standard of care, on the basis of multiple randomized trials demonstrating improved disease control and organ preservation compared with radiotherapy alone. These studies also show that treatment intensification with alternative chemotherapy, induction therapy, or radiation dose escalation does not improve outcomes. Given the curative intent, maintaining quality of life is a key consideration, and current studies are evaluating radiation dose optimization to reduce treatment-related toxicity, as well as the integration of immunotherapy to improve treatment efficacy. In metastatic SCAC, the combination of carboplatin and paclitaxel is the established first-line chemotherapy backbone. The addition of the PD-1 inhibitor retifanlimab to chemotherapy has demonstrated improved clinical outcomes and is now a preferred first-line approach. In the treatment-refractory setting, anti-PD-1 monotherapy provides modest response rates and remains a standard option for immunotherapy-naïve patients. Together, these findings summarize the current evidence base guiding the management of SCAC.
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2026-05-28 | Efficacy and safety of retifanlimab across solid tumors: A systematic review and meta-analysis.
e14585 Background: Retifanlimab is a PD-1 inhibitor with demonstrated activity in several solid tumors, including FDA approved indication in squamous cell carcinoma of the anal canal (SCAC). However, its efficacy and safety across tumor types have not been systematically synthesized. Methods: We conducted a systematic review and meta analysis of prospective trials evaluating retifanlimab in solid tumors. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and oncology conferences were searched through January 2026. Pooled ORR and CR were estimated using random effects models. Subgroup analyses were performed by tumor type, treatment line, and regimen. Results: Nineteen studies encompassing 1,113 patients across phase I-III trials were included. Tumor types included SCAC, Merkel cell carcinoma (MCC), NSCLC, HNSCC, sarcoma, and MSI-H endometrial cancer. Pooled ORR was 57.2% (95% CI, 48.6–65.9%; I² = 87%); CR rate was 26.3% (95% CI, 19.7–32.8%). First-line treatment showed significantly higher ORR than later lines (79.8% vs 39.5%). By tumor type, higher ORRs were observed in HNSCC (74.8%), NSCLC (74.7%), MCC (69.4%), and SCAC (65.4%). Safety was consistent with PD-1 inhibitor class: any-grade irAEs in 27.8%, grade ≥3 in 6.3%. Conclusions: Retifanlimab demonstrates clinically meaningful antitumor activity across multiple solid tumors, with greatest benefit in first line treatment. Consistency of efficacy and safety signals supports ongoing development. Pooled ORR by tumor type. Tumor Studies Patients ORR (95% CI) SCAC 3 402 65.4% (40.7–90.2%) MCC 2 111 69.4% (37.2–101.6%) NSCLC 2 58 74.7% (39.1–110.3%) HNSCC 2 50 74.8% (53.3–96.4%) Sarcoma 3 88 37.5% (21.8–53.2%)
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