Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to late diagnosis and chemoresistance. Patient-derived organoids (PDOs) hold promise for predicting individualized drug responses, but their establishment is often constrained by the limited availability of tumor material and prior neoadjuvant treatment. Standard PDO generation relies on dissected tissue slices from the cut surface of the tumor, which may include both the invasive front, where it is postulated that more aggressive cancer cells reside, and potentially fewer viable neoplastic cells in the tumor center. This study investigated whether scraping the cut surface of the PDAC enhanced PDO establishment compared to standard tissue samples, to take advantage of potential harvesting of viable neoplastic cells from the invasive front. Tumor scrapings from 26 patients and matched tissue slices from 20 patients were collected. PDOs were successfully established from 10 tumor scrapings and eight matched tissue slices, including three neoadjuvant-treated cases. Organoid histological architecture was comparable to the surgical tumor specimens, with paired scraping PDOs and tissue slice PDOs showing genomic and transcriptomic concordance. Pharmacotyping demonstrated that scraping PDOs reliably captured patient-specific chemosensitivity, highlighting the potential for a viable alternative method to standard tissue-slice PDOs. As proliferative and treatment-resistant neoplastic cells often originate from tumor edges, increasing representation of the periphery and across the tumor may offer a more clinically relevant model of PDAC biology, improving therapeutic decision-making and patient outcomes. © 2026 The Pathological Society of Great Britain and Ireland.
Tsang et al. (Mon,) studied this question.