Desmoplastic reaction at the invasive front of upper urinary tract urothelial carcinoma: prognostic impact and associations with tumour invasiveness and immune–inflammatory status

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Desmoplastic reaction (DR), characterised by myxoid stroma and keloid-like collagen, is a poor prognostic factor in several types of cancer. We investigated the impact of stromal DR status on recurrence and prognosis in patients with upper urinary tract urothelial carcinoma (UTUC). This study included 155 UTUC patients who underwent surgery between 1999 and 2021. The presence of myxoid stroma and keloid-like collagen at the invasive front of the tumour was evaluated. Patients were classified into three groups: mature-type, keloid-like, and myxoid-type DR. We analysed the associations between DR status and clinicopathological factors, tumour budding (BD), and tumour-associated immune cell status (TAICs), as well as its impact on extraurothelial recurrence-free survival (EUR-FS) and overall survival (OS). Among the 155 patients, 101 (65%), 15 (10%), and 39 (25%) were classified as mature-type, keloid-like, and myxoid-type DR, respectively. DR status was significantly associated with adverse pathological prognostic factors. In univariate analysis, higher pathological T category, lymphovascular invasion, lymph node metastasis, positive surgical margins, presence of subtype histology, myxoid-type DR, and high-grade BD were significantly associated with worse EUR-FS. Multivariate analysis revealed that myxoid-type DR (HR = 2.19, p = 0.0279) and high-grade BD (HR = 3.35, p = 0.0008) were independent predictors of EUR-FS. Regarding OS, age ≥ 70, lymphovascular invasion, and myxoid-type DR were independent predictors. The presence of myxoid stroma was associated with adverse prognostic factors and low TAICs and served as an independent predictor of EUR-FS and OS. These findings suggest that myxoid stroma in the invasive front represents a novel and useful pathological prognostic indicator for UTUC.

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