Mainstream and fast-track genetic testing in pancreatic cancer patients and its impact on treatment: our experience in a tertiary hospital in Spain.

Germline testing ordered by the oncologist without prior assessment in the hereditary cancer unit, with nurse-facilitated consent and specialist post-test counselling reserved for variants of uncertain significance and pathogenic variants.

Four to ten percent of pancreatic cancers arise from germline variants in BRCA1, BRCA2, PALB2, ATM or MMR genes, and germline testing drives treatment decisions, yet delays remain common. This retrospective descriptive study covers 223 pancreatic cancer patients (55% male, mean age 64 years) who underwent fast-track germline testing at Hospital Gregorio Marañón in Madrid between April 2019 and May 2024, with testing ordered by oncologists after brief pre-test counselling and nurse-facilitated consent and sampling. Pathogenic variants were identified in 32 patients (14.3%) and variants of uncertain significance in 82 (36.7%), half of pathogenic variant carriers not meeting familial pancreatic cancer criteria, and actionable variants were present in 14 of 32 carriers (43.7%), involving BRCA2 (6/32), PALB2 (1/32) and ATM (7/32). Treatment was modified, with PARP inhibitors or platinum-based regimens, in 7 of 223 patients (3%), with a median time from test request to result of 48 days (95% CI 44-52). The authors conclude that mainstream testing is feasible, calling for work on long-term outcomes, cost-effectiveness and psychosocial impact.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This series usefully displays the real cost of mainstreaming in a disease with short prognosis: a median 48-day turnaround and 3% of patients whose treatment changed, against 36.7% left with a variant of uncertain significance to manage. The figure that justifies unselected testing lies elsewhere: half of carriers did not meet familial pancreatic cancer criteria and would have been missed by family history-based ordering. In practice, until turnaround falls below three to four weeks the result arrives after the first-line decision, and that is where the organisational effort belongs, not on broadening indications.

Analysis by Dr Thibaut Benquey