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Background <p>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.</p> Methods <p>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&#xa0;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).</p> Results <p>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&#xa0;kg at T1 to 17.2 ± 3.3&#xa0;kg at T3 (p &lt; 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 &lt; 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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年9月27日

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  • Rizwan Qaisar,
  • Shah Hussain,
  • Firdos Ahmad,
  • Asima Karim

摘要

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.