Prognostic Significance of Procalcitonin in Small Cell Lung Cancer

Kosuke Ichikawa; Satoshi Watanabe; Satoru Miura; Aya Ohtsubo; Satoshi Shoji; Koichiro Nozaki; Tomohiro Tanaka; Yu Saida; Rie Kondo; Satoshi Hokari; Nobumasa Aoki; Yasuyoshi Ohshima; Toshiyuki Koya; Toshiaki Kikuchi


Transl Lung Cancer Res. 2022;11(1):43-52. 

In This Article

Abstract and Introduction


Background: Procalcitonin (PCT) is a serological marker whose utility has been established in infectious disease areas. Although serum calcitonin is a prognostic predictor in patients with medullary thyroid carcinoma, the clinical usefulness of PCT remains unclear in lung cancer patients.

Methods: As a discovery cohort, we retrospectively analyzed consecutive patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) who received first-line chemotherapy at our institution, and PCT blood levels were measured. As the validation cohort, PCT blood levels were prospectively evaluated in SCLC patients before first-line chemotherapy. The correlation between a PCT increase and prognosis was examined in the discovery and validation cohorts.

Results: Twenty-three SCLC patients and 26 NSCLC patients were enrolled as the discovery cohort, and 30 SCLC patients were enrolled as the validation cohort. The PCT level in SCLC patients was significantly higher than that in NSCLC patients. The PCT level was not associated with WBC count and weakly associated with the CRP level. In both the discovery and validation cohorts, the median survival time was significantly shorter in SCLC patients with PCT-high than in SCLC patients with PCT-normal (discovery; 11.7 vs. 89.7 months, P<0.005, validation; 9.6 vs. 22.6 months, P<0.005).

Conclusions: It may be difficult to differentiate bacterial infections in SCLC patients by PCT, as PCT is elevated even in SCLC patients without infectious diseases. This is the first study to prospectively verify that pretreatment PCT levels have a significant negative correlation with prognosis in SCLC patients.


Small cell lung cancer (SCLC) is one of the primary lung cancers of neuroendocrine origin and is strongly associated with smoking and characterized by rapid progression. SCLC is classified into limited disease (LD) and extensive disease (ED) depending on the degree of progression. Because of the sensitivity of SCLC to chemotherapy and radiation therapy, one of the standard initial treatments of SCLC is platinum-based chemotherapy with or without radiotherapy, which is known to cause febrile neutropenia in 10–20% of patients.[1]

Procalcitonin (PCT) is a 13-kDa peptide consisting of 116 amino acids[2] that is usually synthesized in thyroid C cells as a precursor of calcitonin.[3] PCT has a stable half-life of 24 to 30 hours and very low serum levels. In recent years, PCT has attracted attention as an indicator of the severity of bacterial and fungal infections.[4] In addition, compared to conventional inflammatory markers such as C-reactive protein (CRP) and leukocyte count, PCT has superior sensitivity and specificity in bacterial and fungal infections and is used to distinguish it from viral infections and noninfectious diseases.[5] As its clinical usefulness has become known, a precise and simple test method for PCT has been established. The secretion of calcitonin from medullary thyroid carcinoma, SCLC, and neuroendocrine tumors has been reported.[6,7] Specifically, in medullary thyroid carcinoma, an increase in serum calcitonin is known as a prognostic predictor.[5] Neuroendocrine cells in the lung were suggested as the origin of SCLC.[8] Calcitonin related polypeptide alpha encodes calcitonin and calcitonin gene-related peptide (CGPR). Because neuroendocrine cells widely express calcitonin gene related protein, tumorigenesis of these cells may result in elevation of production of PCT and calcitonin. The usefulness of calcitonin as a tumor marker or prognostic factor has been investigated in SCLC, but no conclusion has been reached.[9] Similarly, PCT is also expected to be secreted from SCLC and might be a prognostic predictor in SCLC patients. Indeed, Patout et al. reported that the increase of serum PCT and the negative correlation between serum PCT level and prognosis in patients with lung cancer with neuroendocrine component.[10] However, few reports so far have evaluated the increase in serum levels in patients with SCLC.[11,12] As mentioned earlier, SCLC is usually treated with intense radiotherapy and chemotherapy, and fever often occurs during the course of treatment, but it is not known whether PCT is useful to distinguish between infectious and noninfectious fever when SCLC patients develop fever.

The purpose of this study was to evaluate serum PCT levels in patients with SCLC and to investigate the value of PCT as a prognostic factor. We present the following article in accordance with the STROBE reporting checklist (available at