Patients with colorectal cancer (CRC) undergoing systemic therapy frequently experience functional decline, fatigue, and treatment-related symptoms. Resistance training (RT) is safe during treatment, but the minimum effective duration remains unclear.

To compare the effects of an 8-week versus 12-week supervised RT program on chemotherapy-induced peripheral neuropathy (CIPN) and selected functional, psychosocial, behavioral, and hematological/inflammatory parameters in patients with CRC.

In this pilot randomized clinical trial, 30 adults with CRC were randomized (1:1) to 8 weeks (n = 15) or 12 weeks (n = 15) of supervised RT (2 sessions/week) plus home-based physical activity (3 days/week). The primary outcome was CIPN (EORTC QLQ-CIPN20). Secondary outcomes included handgrip strength, quality of life (EORTC QLQ-C30), anxiety/depression (HADS), physical activity, and hematological/inflammatory parameters.

All participants completed the intervention, with adherence > 90% and no adverse events. No between-group differences were observed in CIPN. Handgrip strength suggested greater adjusted gains in the 12-week group for both dominant (pFDR = 0.026) and non-dominant hand (pFDR = 0.009). Psychological outcomes showed an adjusted between-group difference for HADS total score (pFDR = 0.022). Exploratory analyses suggested a reduction in NLR after 12 weeks (p = 0.043), with no significant adjusted between-group differences. Nominal between-group differences in fatigue and gastrointestinal symptoms were observed only in unadjusted analyses.

Supervised RT during systemic treatment in CRC appears feasible and safe. In this pilot dose-comparison trial, both programs were associated with improvements in selected outcomes, although efficacy cannot be established. A 12-week duration may be associated with additional benefits; however, findings are exploratory. Larger trials including usual-care controls are needed.

The clinical trial was registered in ClinicalTrials.gov (NCT07307690) on 1 January 2026.