Methodological clarifications of perioperative nutritional outcomes: a response to Ma et al.

We would like to thank Dr Longtu Ma, Dr Zeming Qiu, and Prof. Zhilong Dong for their interest in our study [1], and for their detailed comments regarding perioperative nutritional optimisation following radical cystectomy (RC) [2]. We welcome the opportunity to address points raised and to clarify the intent and the interpretation of our findings. Regarding endpoint alignment, the study was prospectively powered to detect a reduction in 30-day postoperative complications, which did not reach statistical significance. This result was reported transparently without claims of superiority made, despite a directionally favourable trend in the intervention group. Instead, our conclusions were appropriately based on pre-specified secondary endpoints that demonstrated consistent, statistically robust, and clinically meaningful benefits. While postoperative complications remain an established benchmark in RC, recovery-related and functional outcomes are now widely recognised as core indicators of perioperative success within enhanced recovery after surgery (ERAS) pathways [3]. In complex, high-morbidity procedures such as RC, these metrics provide critical insight into physiological resilience and patient-centred recovery. In this context, our findings do not dilute complication-based benchmarks but rather extend them by demonstrating measurable recovery benefits without any compromise in safety. We acknowledge that hierarchical testing strategies or composite endpoints may further strengthen future trials. The multicomponent nature of the nutritional intervention was an intentional design choice. Perioperative nutrition in contemporary ERAS practice is inherently multimodal, and evaluating isolated components would have limited clinical relevance [3]. Our objective was therefore to assess the effectiveness of a structured, dietitian-led nutritional optimisation pathway as it is implemented in routine practice. The observed benefits are most plausibly attributable to synergistic effects among immune-enhancing substrates, individualised caloric and protein targets, behavioural counselling, and systematic monitoring. While factorial designs may offer mechanistic refinement, they should complement rather than replace pragmatic effectiveness studies. Concerns regarding complete retention and adherence should be interpreted in the context of the study design. The absence of withdrawals reflects the single-centre setting, short perioperative follow-up, inpatient delivery of intervention components, and integration of nutritional optimisation into standard care pathways. Importantly, adherence was not uniform across all elements. As shown in Table 1 of our paper [1], component-specific adherence ranged from approximately 81–100%, providing a realistic depiction of compliance. Although close monitoring may have improved adherence and possibly increased the observed effect size, the intervention protocols proved to be feasible and reproducible in centres with established ERAS programmes. We agree that future multicentre studies should incorporate formal adherence and implementation analyses. Finally, regarding serum albumin, the variability in exposure duration reflects real-world surgical scheduling rather than methodological inconsistency. Baseline albumin levels were comparable between both groups before surgery as shown in Fig. 2 of our paper [1], and diverged only following nutritional optimisation, supporting an intervention-associated effect. Nonetheless, we recognise the limitations of albumin as a short-term nutritional marker [4] and have explicitly acknowledged this. In conclusion, we appreciate the authors’ constructive critique. Our data provide evidence that structured, dietitian-led perioperative nutritional optimisation is a safe, feasible, and a clinically effective strategy to enhance recovery after RC. The authors declare no conflict of interest.