Elevated Platelet Count as Predictor of Recurrence in Rectal Cancer Patients Undergoing Preoperative Chemoradiotherapy Followed by Surgery

The impact of systemic inflammatory response (SIR) on prognostic and predictive outcome in rectal cancer after neoadjuvant chemoradiotherapy (CRT) has not been fully investigated. This retrospective study enrolled 89 patients with locally advanced rectal cancer who underwent neoadjuvant CRT and for whom platelet (PLT) counts and SIR status neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR)] were available. Both clinical values of PLT and SIR status in rectal cancer patients were investigated. Elevated PLT, NLR, PLR, and pathologic TNM stage III ypN(+)] were associated with significantly poor overall survival (OS). Elevated PLT, NLR, and ypN(+) were shown to independently predict OS. Elevated PLT and ypN(+) significantly predicted poor disease-free survival (DFS). Elevated PLT was identified as the only independent predictor of DFS. PLT counts are a promising pre-CRT biomarker for predicting recurrence and poor prognosis in rectal cancer.Key words: Platelet, Neutrophil/lymphocyte ratio, Platelet/lymphocyte ratio, Rectal cancer, Prognosis, ChemoradiotherapyPreoperative chemoradiotherapy (CRT) and total mesorectal excision for the management of locally advanced rectal cancer (LARC) have significantly decreased local recurrence rates and improved sphincter preservation and patient survival.^1,2 However, distant recurrence remains the major cause of mortality in patients who undergo preoperative CRT followed by Total Mesorectum Excision (TME). Further improvements in the survival rate cannot be achieved without the control of postsurgical distant recurrence.Postoperative histopathologic features such as surgical margins (achievement of R0 resection) and lymph node metastases are recognized as predictors of local and distant recurrence in rectal cancer patients treated by preoperative CRT.^3–5 However, preoperative serum markers that could predict recurrence and/or poor prognosis⁶ might present a convenient tool to permit intensification of either preoperative neoadjuvant or postoperative adjuvant chemotherapeutic strategies.Aberrant activation of platelets (PLT) and the coagulation pathway are associated with malignancies. Increased PLT count may indicate poor prognosis in cancer patients,^7,8 nearly a third of whom have thrombocytosis at diagnosis and before treatment,⁹ although the mechanisms by which thrombocytosis develops in malignancies remains unknown. Particularly in colorectal cancer, the prognostic significance of thrombocytosis was recently reported by Ishizuka et al and Cravioto-Villanueva et al.^10,11 Pretreatment thrombocytosis is also a predictor for CRT response and local recurrence in rectal cancer patients.¹²However, the systemic inflammatory response (SIR), which is thought to be secondary to hypoxia or tumor necrosis, is associated with anti-apoptotic characteristics in cancer cells¹³ and has been shown to act as a biomarker of outcome in a variety of malignancies.¹⁴ Neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) are two representative indexes of systemic inflammation; their prognostic values have been studied in many cancer types.¹⁵ High NLR or PLR reportedly predicts poor outcomes in colorectal cancer patients who undergo primary resection without lymph node metastases and who undergo hepatectomy for liver metastasis.^16–18 Recently, the clinical significance of NLR in rectal cancer patients undergoing CRT followed by surgery has been demonstrated, showing that it was predictor for recurrence and overall survival.¹⁹In this study, we investigated the correlations between levels of PLT, NLR, and PLR in pretreatment blood tests, and clinicopathologic features in patients who undergo CRT followed by TME for locally advanced rectal cancer, and evaluated and compared their potentials as prognostic biomarkers.