Pathology is not merely diagnostic support in modern cancer trials; it is fundamental infrastructure that connects the clinical question to specimen workflows, assays, endpoints, and decision timing. Pathologists play active roles in tumour classification, staging, biomarker interpretation, eligibility assessment, response assessment, and endpoint evaluation. In biomarker-led, adaptive, umbrella, and window-of-opportunity studies, pathology-derived measures may serve as primary or key secondary endpoints rather than being limited to exploratory analyses.
Embedding pathology expertise into trial design facilitates practical tissue acquisition strategies. Pathologists advise on the quantity, quality, and processing of material required for downstream molecular and cellular assays. They work alongside surgeons, interventional radiologists, oncologists, trial managers, cancer biologists, and laboratory scientists to align clinical sampling with the scientific aims and decision points of the study. This multidisciplinary planning reduces avoidable repeat procedures, preserves tissue needed for patient care, decreases screen failures due to insufficient material, and helps ensure assays and response assessments can be delivered reproducibly within recruitment and treatment timelines.
Where trials depend on biological material, pathology input is therefore woven into trial architecture: it links the intervention to the mechanism being studied through coherent specimen pathways, validated assays, and clear endpoint definitions. The literature and consensus documents cited by the authors underscore that pathology is a necessary and informative tool in oncology clinical trials and that active pathology involvement already exists in many established clinical trials units.
For biologically driven cancer trials, pathology planning should be visible and operational before funding submission, while protocols, budgets, timelines, and laboratory workflows remain modifiable. Early input is not intended to duplicate existing expertise but to ensure a consistent framework where tissue handling, assay delivery, endpoint assessment, and translational use of samples are explicit parts of the protocol.
The SPIRIT-Path extension—developed through international consensus—provides specific guidance on the cellular and molecular pathology content that should appear in clinical trial protocols. SPIRIT-Path recommends defining who is responsible for pathology activities, where analyses will be performed, applicable accreditation and quality systems, specimen movement between sites and laboratories, and how tissue will be used for both protocol-defined and future translational work. These protocol-level details determine whether patients can be screened efficiently, whether biomarker results can be returned in time for treatment allocation, whether samples are suitable for primary or key secondary endpoints, and whether response assessments can support interim go/no-go decisions.
Early pathology planning strengthens trial readiness by reducing avoidable screen failures, failed samples, protocol amendments, and loss of material needed for translational analyses. It also ensures that consent processes, specimen governance arrangements, and laboratory costing are aligned with the study’s scientific aims before funding decisions are finalised. The authors note that work is ongoing to update and remap SPIRIT-Path to align with subsequent SPIRIT guidance so that this framework remains relevant.
Questions posed by modern oncology CTIMPs increasingly include not only whether an intervention works but who benefits, whether the intended pathway has been engaged, how resistance emerges, and which biomarkers should guide future studies or implementation. Answering these questions depends on the robustness of translational endpoints, which in turn rely on specimen quality, validated assays, and reliable laboratory systems.
The pre-analytical phase is especially critical. Factors such as specimen fixation, processing delays, decalcification, storage conditions, and tumour cellularity all influence downstream molecular performance. Degraded nucleic acid, low tumour purity, or unrecognised pre-analytical variation can render translational readouts uninterpretable even when samples have been collected. Similarly, narrow consent can restrict secondary analyses and reduce the long-term value of collected tissue. Early pathology involvement helps to anticipate and mitigate these risks by specifying acceptable pre-analytical conditions and appropriate consent language.
Biologically rich trials may also aim to capture spatial biology through multiplex imaging and spatial-omics, which place further demands on tissue handling, annotation, and analytical standardisation. Early pathology planning is required to preserve tissue architecture and metadata needed for these approaches and to ensure reproducible analysis across sites and platforms.
Practical UK examples illustrate the benefits of rigorous pathology and laboratory planning. The FOCUS4 umbrella trial in metastatic colorectal cancer embedded molecular profiling and required pre-trial inter-laboratory validation before testing was used for cohort allocation; across the study, a large series of tumour samples were analysed with low assay failure rates and at least 98% concordance between laboratories where both produced a result. The National Lung Matrix Trial used central molecular profiling to allocate patients with non-small cell lung cancer to genotype-matched treatment cohorts at national scale. plasmaMATCH demonstrated that circulating tumour DNA testing could identify actionable genomic alterations in advanced breast cancer and direct cohort assignment across UK sites without requiring repeat tumour biopsy in every patient. These examples show that pathology and laboratory design are not ancillary to complex biomarker trials; they are integral to how such trials function at scale.
Conclusion
The Perspective argues that pathology should be treated as core infrastructure in biologically rich cancer trials. Embedding pathology expertise early in trial development improves feasibility, assay delivery, specimen governance, and the long-term translational value of samples, and it ensures that translational endpoints meaningfully connect interventions to biological mechanisms. Where available, practical routes for pre-submission specialist review—for example via national pathology advisory groups—can help operationalise early pathology input in trial proposals.