Plasma CAF22 and NfL reflect neuromuscular decline during cisplatin-based chemotherapy and radical cystectomy in muscle-invasive bladder cancer.

Abstract

Background: Cisplatin-based chemotherapy and radical cystectomy are standard treatments for muscle-invasive bladder cancer (MIBC), but their impact on neuromuscular integrity and functional capacity remains elusive. We investigated plasma biomarkers of neuromuscular junction degradation (c-terminal agrin-fragment-22; CAF22) and neuronal injury (Neurofilament light-chain; NfL) in relation to physical capacity in MIBC patients.

Methods: In this prospective study, 42 MIBC patients undergoing neoadjuvant cisplatin-gemcitabine chemotherapy and radical cystectomy were assessed before (T1) and after (T2) chemotherapy, and 4-6 weeks post-surgery (T3). Age- and BMI-matched controls (n = 46) were evaluated once. Plasma CAF22 and NfL were measured alongside handgrip strength (HGS), gait speed (GS), appendicular skeletal muscle index (ASMI), and short physical performance battery (SPPB).

Results: Plasma CAF22 and NfL were significantly elevated in patients versus controls at all time points. NfL showed more modest increases in post-treatment. HGS declined from 22.3 ± 3.9 kg at T1 to 17.2 ± 3.3 kg at T3 (p < 0.05), along with reductions in ASMI and GS. Cumulative SPPB scores dropped from 9.02 ± 1.02 to 8.24 ± 1.32. Sarcopenia prevalence rose from 28.5% at T1 to 52.4% at T3. CAF22 was significantly associated with lower HGS and SPPB at T1 (β = - 0.58 and - 0.42, p < 0.001). CAF22 changes correlated with HGS (r = - 0.80) and SPPB (r = - 0.75), while NfL showed weaker but significant correlations. Lab results indicated declines in hemoglobin, albumin, and renal function markers consistent with treatment effects.

Conclusions: CAF22 showed strong associations with treatment-related decline in skeletal muscle, suggesting its potential as an early biomarker of sarcopenia that warrants validation in larger cohorts.