Evidence and Clinical Decision-Making in Rare Solid Tumors: Challenges, Current Practice, and Future Directions

Rare solid tumors are individually uncommon but collectively account for a substantial share of all cancer diagnoses. Patients with these malignancies consistently face worse outcomes than those with common cancers, and the reason is rarely biological alone: the evidence base that guides their care is thin. Randomized controlled trials are often difficult to adequately power and may face prolonged accrual, single-arm and basket designs dominate, and much of clinical practice relies on extrapolation from related histological or molecular subgroups, retrospective series, registry data, and expert consensus. As a result, clinicians are routinely asked to make consequential decisions under a level of uncertainty that would be unacceptable in common tumor types.This uncertainty has practical consequences across the whole patient pathway. Diagnosis is frequently delayed or revised after expert pathology review. Access to comprehensive molecular profiling, tumor-agnostic therapies, and clinical trials varies widely between centers, regions, and health systems. Referral to high-volume expert centers improves outcomes but is inconsistently implemented. Regulatory approval and reimbursement decisions must weigh evidence that is, by definition, incomplete. Meanwhile, methodological advances — Bayesian and adaptive designs, external and synthetic control arms, real-world evidence, federated multicenter registries, molecular tumor boards, and AI-supported decision support — are reshaping what “adequate evidence” can mean in a low-incidence setting.This Research Topic aims to bring together clinical, methodological, and health-systems perspectives on how evidence is generated, appraised, synthesized, and translated into decisions for patients with rare solid tumors. We are particularly interested in work that moves beyond describing evidence scarcity toward proposing, testing, or evaluating solutions. The Topic will explore innovative approaches to evidence generation and synthesis, the integration of real-world and registry data, multidisciplinary and molecular decision-making, and strategies to address diagnostic, therapeutic, regulatory, and access-related uncertainties. By bringing together original research, systematic reviews and meta-analyses, methodological studies, and critical perspectives, we aim to identify practical approaches that can strengthen the evidence base and support more informed, equitable, and patient-centered decision-making across rare solid tumors. We welcome contributions addressing, but not limited to:o Evidence generation in low-incidence settings: adaptive, basket, umbrella, and platform trials; external and synthetic control arms; Bayesian approacheso Real-world data, national and international registries, and federated data networkso Evidence synthesis: systematic reviews, meta-analyses, comparative effectiveness research, and approaches to synthesizing heterogeneous or limited datao Multidisciplinary and molecular tumor boards: composition, workflow, concordance, and measurable impact on outcomeso Diagnostic accuracy, central pathology review, and the role of comprehensive genomic profilingo Biomarker-driven and tumor-agnostic therapies: patient selection, access, and clinical outcomes o Guideline development and consensus methodology when high-level evidence is unavailableo Centralization, referral networks, and geographic or socioeconomic disparities in accesso Regulatory, HTA, and reimbursement pathways for rare tumor therapeuticso Patient-reported outcomes, quality of life, shared decision-making, and the patient advocacy perspectiveo Artificial intelligence and clinical decision support applied to rare tumor managementTopic Editor Dr. Salvatore Provenzano's institution has received research funding from Abbisko Therapeutics Co. Ltd., Advenchen, Ayala Pharmaceuticals, Blueprint, Boehringer Ingelheim, Cogent Biosciences, Daiichi Sankyo, Deciphera, EISAI, Eli Lilly, Epizyme Inc., Foghorn, GlaxoSmithKline, HUTCHMED, Immunome, IDRX, Inc., Inhibrx, Karyopharm, Novartis, PharmaMar, Rain Therapeutics, SpringWorks and Syneos Health. Dr. Provenzano's spouse is employed by AstraZeneca. All other Topic Editors declare no competing interests with regard to the Research Topic subject.Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: Nazim Demircan, Herbert Loong, Salvatore Provenzano Source: https://www.frontiersin.org/research-topics/85617/evidence-and-clinical-decision-making-in-rare-solid-tumors-challenges-current-practice-and-future-directions