# An Audit of Accessibility and Actionability of Molecular Profiling for Patients with Cancer of Unknown Primary at a Tertiary Care Centre

**Authors:** Khaled Abdulalem, Jonah Teich, Erika Martinez, Samuel D. Saibil

PMC · DOI: 10.3390/clinpract16020039 · 2026-02-12

## TL;DR

This study examines how often cancer patients with unknown primary tumors receive molecular testing and finds that it is rarely used early enough to change their treatment.

## Contribution

The study reveals low accessibility and late use of molecular profiling in CUP treatment, suggesting a need for earlier integration into clinical practice.

## Key findings

- 82% of patients received NGS analysis, but only after their disease had progressed.
- Only 13% of patients had their treatment modified based on molecular profiling.
- Molecular profiling was accessed through clinical trials, charitable programs, or private sources, not standard hospital services.

## Abstract

Background/Objectives: Cancer of unknown primary (CUP) remains a significant challenge in the field of oncology. Despite advances elsewhere in the field, there have been few advances in the treatment of CUP and correspondingly no improvements in patient survival. Recent studies utilizing molecular profiling, including next-generation sequencing (NGS), and molecularly targeted treatment of CUP have shown some promising initial results, but have yet to be integrated into the standard of care in most jurisdictions. This study aimed to assess the use of molecular characterization and targeted treatment of patients with CUP treated at Princess Margaret Cancer Centre (PMCC). Methods: This study is a retrospective audit of patients with CUP treated between January 2019 and April 2024 to build understanding of the accessibility and use of these molecular tools. Results: We found that 82% of the 28 patients identified received NGS analysis, though all received the results late in their disease course and all accessed molecular profiling via either clinical trials, a charitable access programme, or a privately source outside of the hospital network. Only 13% of the patients who received molecular analysis received any modification of care as a result of this profiling, and only as third line of treatment. Conclusions: Our data highlights a lag between current understanding and current practice, and identifies a possible area for improvement of patient care by standardizing the use of molecular analysis in the early workup and targeted therapy in the treatment of CUP.

## Full-text entities

- **Genes:** KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290] {aka CCM4, CLAPO, CLOVE, CWS5, HMH, MCAP}, BRCA2 (BRCA2 DNA repair associated) [NCBI Gene 675] {aka BRCC2, BROVCA2, FACD, FAD, FAD1, FANCD}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, KRT19 (keratin 19) [NCBI Gene 3880] {aka CK19, K19, K1CS}, TSC2 (TSC complex subunit 2) [NCBI Gene 7249] {aka LAM, PPP1R160, TSC4}, KRT7 (keratin 7) [NCBI Gene 3855] {aka CK7, K2C7, K7, SCL}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}
- **Diseases:** carcinoma NOS (MESH:C536665), metastases (MESH:D009362), sarcomatoid carcinoma (MESH:D002292), adenocarcinoma (MESH:D000230), CUP (MESH:D009369), spindle cell carcinoma (MESH:D002277), injury to (MESH:D014947), squamous cell carcinoma (MESH:D002294)
- **Chemicals:** capecitabine (MESH:D000069287), ivosidenibe (-), Everolimus (MESH:D000068338), taxanes (MESH:D043823), platinum (MESH:D010984), lapatinib (MESH:D000077341)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** c.2521C>T, c.35G>A, 4514delGc, c.346G>A, c.1454T>G, c.5965T>C, c.3103C>T, c.394C>T, c.4513C>T, c.2335C>T, c.567C>A, c.157G>A, c.182A>G, 1009C>T, c.2998C>T, 3140A>G, c.6713G>C, 8107C>T, c.97T>C, c.109A>G, c.2176G>A, c.59C>T, c.1330delA, c.1747A>G, c.2485G>A, c.781C>T

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939395/full.md

---
Source: https://tomesphere.com/paper/PMC12939395