Platelet to lymphocyte ratio as an independent prognostic indicator for prostate cancer patients receiving androgen deprivation therapy

Despite recent progress in the identification of genetic and molecular alterations in prostate cancer (PCa), the routine prognostic risk assessment of PCa patients currently relies on traditional clinicopathological prognostic factors, including Gleason score, clinical tumor stage, and serum PSA level at the time of diagnosis, which are used for stratify the patients into the low-, intermediate-, or high-risk group [19]. The predictive accuracy of this traditional prognostic model need be further improved by the incorporation of novel prognostic biomarkers.

The platelet and lymphocyte counts are routinely measured blood-based parameters. In this large cohort of PCa patients treated with androgen deprivation therapy (ADT), we found that pretreatment high platelet to lymphocyte ratio (PLR) was associated with increased risk for disease recurrence, cancer specific mortality and all-cause mortality. These findings remained significant after adjusting for clinicopathological features, indicating an independent association of high pretreatment PLR with adverse outcomes.

An exact explanation for this observation remains unclear and is yet to be elucidated. The PLR represents a marker of inflammation. A high PLR reflects both an elevated platelet dependent pro-tumor reaction and a decreased lymphocyte mediated anti-tumor immune response, which may both contribute to cancer progression and poor outcome. Platelets have been shown to promote cancer growth and metastasis. For instance, Boucharaba A et al. [21] showed platelet-derived lysophosphatidic acid was critical for bone metastasis formation in breast cancer. Dashevsky O et al. [22] demonstrated platelet-derived microparticles promoted invasiveness of PCa cells via upregulation of MMP-2 production. Zheng S et al. [23] found, in PCa, fibrinogen help platelets to adhere to tumor cells, and platelets in turn promoted more fibrinogen to aggregate around tumor cells by forming thrombin, and thus protected tumor cells from natural killer cell cytotoxicity, which was mediated by β3-integrins. There is considerable evidence that lymphocytes represent the cellular basis of cancer immunosurveillance, which inhibit tumor cell proliferation and metastasization [24]. Huang SH et al. [25] showed pretreatment high circulating lymphocytes could predict better recurrence-free survival and marginally better overall survival in HPV⁺ oropharyngeal cancer patients. Adams S et al. [26] confirmed tumor stromal lymphocytic infiltration constituted a robust prognostic factor in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials. However, the differences of tumor features including age, serum PSA level, Gleason score, risk stratification and incidence of metastasis between low PLR group (<117.58) and high PLR group (≥117.58) were not significant in our study.

To date, adverse clinical outcomes of many cancers have been associated with an elevated PLR [8–15]. Zhou X et al. [27] performed a meta-analysis on the prognostic value of PLR in various cancers, and found that elevated PLR was a negative predictor for OS with HR of 1.60 (95 % CI 1.35–1.90, P < 0.001). Similarly, Templeton AJ et al. [28] conducted a systematic review and showed that a high PLR was associated with worse OS in various solid tumors.

In contrast to the well-known prognostic value of PLR in other malignancies, its value in PCa is poorly studied. Only two studies exist regarding the association of PLR and PCa outcomes. In 384 patients treated with 3D conformal radiotherapy from 1999 to 2007, Langsenlehner T et al. [18] noted an increased PLR (≥190) was a significant prognostic factor for poor distant metastases-free survival, cancer-specific survival and overall survival. Importantly, intergroup inconsistent neo-adjuvant therapy and potential confounding factors like inflammatory diseases may affect their study results. In 2015, Li F et al. [29] evaluated the relationship between PLR ≥150 and all cause mortality in 103 PCa patients, and found that PLR was an independent risk factor of 3-year mortality, However, their analysis was limited by its relatively small patient population and intergroup inconsistent therapy.

To the best of our knowledge, our analysis is the first study of PLR on the prognosis of PCa treated with ADT, and strikingly our results showed that PLR was an independent prognostic factor for PFS, CSS and OS. Comparing to previous studies, we made a subgroup analysis and built a new integrated prognostic model. In subgroup analysis, we found that high PLR could predict poor prognosis in the subgroup of patients with Gleason score >7 or bone metastasis. In the subgroup of Gleason score ≤7 or non-metastasis, however, PLR was not statistically significantly associated with prognosis, probably because the percentages of patients who reached the endpoints (progression, cancer-related death and overall death) in this subgroup were too small. With the traditional prognostic base model, which includes only Gleason score and incidence of metastasis, the predictive accuracy was 73.0, 77.8 and 74.6 % for PFS, CSS and OS, respectively. The predictive accuracy was clearly improved by the addition of PLR (74.7, 80.1 and 76.8 %).

There are some limitations to our current study. First, this was a retrospective investigation. Despite the strict enrollment criteria applied, we were unable to completely exclude conditions that might cause inflammatory changes in PCa. Second, the patient data were collected from a single institution. Our results need to be validated by prospective research and patient data from multiple medical centers.