What’s known on the subject? and What does the study add?
The literature data used to predict early recurrence of localized prostate cancer need to be expanded, but studies should be continued.
Introduction
Although prostate cancer is now accepted as an important cause of male deaths, the mystery over the behavior of cancer cells is still ongoing. Prostate-specific antigen (PSA) screening can be used in the diagnosis of early-stage prostate cancer, but the pathological features of cases undergoing radical surgery continue to be questioned. For this reason, there is still a need to update the information on prostate cancer. The relationship between cancer formation and inflammation has become a very interesting subject nowadays and the evidence about the link between these two conditions is increasing day by day. It has been shown that increased angiogenesis as a result of inflammation caused by infection, autoimmunity, chronic irritation, and tumor and resulting from treatments, contributes to carcinogenesis (1). The relationship between tumor survival and inflammation has been tried to be shown using neutrophil-lymphocyte ratio (NLR) in many cancer types. It is known that platelets play an important role not only in achieving hemostasis but also in inflammatory reactions and in immunological responses (2,3,4,5). Mean platelet volume (MPV) has been previously reported to be a marker of platelet activation, but, recently, platelet mass index (PMI) calculated by multiplying platelet count by MPV was claimed to be a better parameter of inflammation than MPV in a study (6,7).
In this retrospective study, we aimed to investigate the association of preoperative PMI with tumor pathologic features and postoperative biochemical recurrence in patients undergoing radical prostatectomy due to localized prostate cancer.
Materials and Methods
Data of patients, who underwent radical prostatectomy for localized prostate cancer at Zonguldak Bülent Ecevit University, Health Practice and Research Center, Clinic of Urology between April 2004 and April 2017 by four expert surgeons in urooncology, were retrospectively screened following the approval of Bülent Ecevit University Local Ethics Committee (protocol number: 2018-23-17/01). Using hospital records, patients’ age, preoperative PSA, platelet count, MPV and PMI value, NLR, tumor grade, Gleason score, tumor volume, lymph node involvement, surgical margin positivity, and biochemical recurrence at 3 months were analyzed. A total of 141 patients with written consent and at least 6 months of follow-up were included in the study. PMI value was examined in relation to age, PSA, pathologic parameters, surgical margin positivity and biochemical recurrence. Biochemical recurrence was accepted when an additional treatment started at the third month control with an increase of PSA value or if there was a persistent increase in PSA value at the 6th month control.
Statistical Analysis
Mean, standard deviation, median lowest, highest, frequency and ratio values were used in the descriptive statistics of the data. The distribution of the variables was measured by the Kolmogorov-Smirnov test. The Kruskal-Wallis test and the Mann-Whitney U test were used in the analysis of quantitative independent data. In correlation analysis, the Spearman correlation coefficient was used. SPSS 18.0 program was used for statistical analysis.
Results
The mean age of the patients was 61.79±5.98 years, the mean PSA value was 9.50±6.69 ng/mL, the mean PMI was 2003.91±486.69, and mean NLR was 2.79±2.06. The preoperative data of the patients are summarized in Table 1. The mean tumor volume was 9.20±8.42 cm3. Four (2.8%) patients had lymph node involvement, while 66 (47.6%) patients had positive surgical margin; 25 (17.5%) patients had biochemical recurrence at the third month control. The distribution of patients according to preoperative PSA levels and pathologic variables is shown in Table 2. The relationship between surgical margin involvement and histopathological findings is shown in Table 3. There was no correlation of PMI value with PSA, pathological stage, Gleason score, lymph node involvement, tumor volume, surgical margin positivity, and biochemical recurrence (Table 4). The correlation of NLR with PSA, pathological stage, Gleason score, lymph node involvement, tumor volume, surgical margin positivity, and biochemical recurrence is shown in Table 5. NLR was statistically significantly lower in lymph node-positive patients. Analysis of correlation between NLR and age, PSA, Gleason score and tumor volume and between PMI and age, PSA, Gleason score and tumor volume are shown in Table 6. There was a statistically significant negative correlation between PMI and Gleason score.
Discussion
It is known that the development of tumor cells in our body activates an inflammatory response. Systemic inflammation also suppresses the anti-tumor immune system, thus facilitating cancer progression and metastasis (8,9,10,11,12,13). Previously, biomarkers of inflammation, such as NLR, platelet-lymphocyte ratio and C-reactive protein, have been shown to be valuable prognostic factors in many cancers (8,10,11,12,14,15,16,17). During the inflammatory process, many mediators that activate thrombocytes are released. Platelets secrete various growth factors that support angiogenesis, cell proliferation and metastasis (15,16,17,18,19). Tumor-associated thrombocyte aggregation forms a barrier against T-cells by forming a protective shield around the tumor cells (20,21).
While localized prostate cancer treatment and follow-up schemes are created, many biochemical and pathological data are benefited from. Prostate cancer may show differences between treatment strategies when cases become resistant to castration. Thus, the idea of using simple blood tests to guide the experts is available for a long time. NLR is the most studied parameter for this purpose. However, in the literature, we have not seen any study evaluating such a relationship with PMI in prostate cancer.
In our study comparing the NLR with preoperative PSA value, pathologic data and the presence of biochemical recurrence in patients with localized prostate cancer undergoing radical prostatectomy, NLR was lower in lymph node-positive patients and it was statistically significant. Unlike our work, a significant correlation was found between high NLR and lymph node positivity in a study with 1688 patients performed by Zhang et al. (22). However, in their study with 217 cases, Kwon et al. (23) found a positive relationship only between NLR and Gleason score. On the other hand, we did not observe a relationship with other parameters.
PMI is a biomarker that has recently attracted the attention of researchers. In the first study about PMI, it has been reported that unnecessary platelet transfusions in neonatal intensive care units could be prevented (24,25,26,27). There is an inverse relationship between platelet count and platelet volume in order to keep PMI stable, and therefore platelet activity at a constant value. Apart from PMI value, high MPV value and larger platelet diameter were found to be associated with increased platelet activity (28).
It is seen in the literature that MPV has different prognostic significance in different cancers. However, how MPV values affect prognosis remains to be discussed. High MPV value is significant in breast and hepatocellular carcinomas, but it gains significance when decreasing in lung cancer (29,30,31,32,33). It is not possible to reach a definite result with MPV today. Elevation in platelet count was found to be associated with metastasis development and poor prognosis in some solid cancers (34,35). This is being explained by the overproduction of megakaryocyte colony-stimulating cytokines (36). On the other hand, it has been also claimed that platelets act as a protective shield against circulating tumor cells (37). Takeuchi et al. (38,39) showed that the higher the platelet counts and platelet-lymphocyte ratio the poorer the prognosis of breast cancer. The prognostic value of increase in the number of platelets in renal cell carcinoma cases has also been investigated, but the results were different from each other (36).
In this pioneer study, a negative correlation between PMI and Gleason score was found which was to be statistically significant. We assume that the low number of patients may be misleading. We did not observe a statistically significant difference between PMI values and biochemical recurrence among patients.
Study Limitations
There were some limitations in this study. First, the retrospective nature of the study makes it difficult to obtain generalizable results. The lack of long-term follow-up results of patients was the other limitation of this study. The low number of patients treated at a single institution also weakens the power of influence of the study.
Conclusion
Our study demonstrates that preoperative PMI is not a prognostic factor for early biochemical recurrence in patients undergoing radical prostatectomy for prostate cancer. When the literature is examined, it is emphasized that platelet count and platelet volume may be prognostic factors in some advanced cancers. To achieve the same result for PMI values in prostate cancer, there is a need for prospective studies with larger patient series.
Ethics
Ethics Committee Approval: This study was approved by Bülent Ecevit University Local Ethics Committee (protocol number: 2018-23-17/01).
Informed Consent: Written consent was taken from all patients.
Peer-review: Externally peer-reviewed.
Authorship Contributions
Surgical and Medical Practices: R.G., E.B., Ö.Ç., Concept: R.G., Design: R.G., Data Collection or Processing: C.F.Ö., E.B., Analysis or Interpretation: R.G., E.B., Ö.Ç., Literature Search: C.F.Ö., Writing: R.G.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.
