Prognostic Nutritional Index as a Predictor of Surgical Morbidity in Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

<b>Background:</b> The management of locally advanced rectal cancer (LARC) has seen the emergence of total neoadjuvant therapy (TNT) as a promising approach. TNT has shown potential in enhancing tumor regression, increasing pathological complete response (pCR) rates, and improving the control of systemic disease. However, the impact of TNT on complications during and after surgery remains uncertain. This research aimed to assess surgical complications linked to TNT in comparison with conventional neoadjuvant chemoradiotherapy (nCRT). Additionally, this study explored the potential of the Prognostic Nutritional Index (PNI) as a predictor of surgical outcomes. <b>Methods:</b> A retrospective cohort study was conducted at Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, including patients with LARC who underwent either TNT or nCRT followed by curative excision (TME). Demographic data, perioperative complications, and tumor-related variables were also analyzed. The prognostic value of the PNI in predicting surgical complications was assessed using multivariate logistic regression analysis. Statistical significance was set at <i>p</i> < 0.05. <b>Results:</b> A total of 103 patients with LARC were included, of whom 38 (36.9%) received TNT and 65 (63.1%) underwent nCRT. TNT was associated with significantly higher rates of anastomotic leakage (13.2% vs. 6.2%, <i>p</i> = 0.04) and wound infections (23.7% vs. 9.2%, <i>p</i> = 0.02). The mean tumor size was significantly smaller in the TNT group (3.22 ± 1.10 cm) than in the nCRT group (3.65 ± 1.26 cm, <i>p</i> = 0.02). The PNI was significantly lower in the TNT group (38.96 ± 5.54) than in the nCRT group (41.31 ± 4.65, <i>p</i> = 0.03). Multivariate logistic regression analysis demonstrated that a lower PNI was independently associated with increased surgical complications (β = -1.09, <i>p</i> = 0.028, 95% CI: -2.06--0.12). <b>Conclusions:</b> Although TNT demonstrates clear oncological benefits in LARC, it is associated with increased perioperative morbidity. Our findings suggest that the PNI is a valuable predictive biomarker of surgical complications in patients treated with TNT. Preoperative nutritional assessment and optimization may improve perioperative outcomes and mitigate the risks associated with TNT. Future prospective studies should explore targeted interventions to enhance the safety profile of TNT while preserving its oncological advantages.