There were a total of 944 patients who underwent RTPB at the Department of Urology, Singapore General Hospital between Sep 2006 and Feb 2016 (Figure 1). Among these patients 93 were excluded due to missing NLR and PSA parameters. Fourteen patients with biopsy results of HGPIN and chronic inflammation were also excluded. In addition, 141 patients who underwent biopsy for non diagnostic purposes (eg. Brachytherapy, active surveillance) were also excluded.
Among 44 cases who had more than one biopsies, only the last histology results were included in this study.
A total 652 patients who underwent RTPB for diagnostic purpose with valid pre-procedure PSA level were included in this study. Clinical demographics were shown in Table 1. Median PSA before biopsy was 8.9 ng/ml and median number of cores taken was 29 and overall median NLR was 2.00.
As shown in Table 2, there was no statistically significant difference of NLR between the benign and prostate cancer group (P=0.29).
If defined Gleason 3 + 4 and above as clinical significant prostate cancer, there was no statistically significant difference of median NLR value in the clinical significant cancer group compare to benign histology group (Table 3, figure 1). We also compared NLR value in prostate cancer group and benign group according to different pre-biopsy PSA level. However, there was no statistically significant difference in the various PSA levels (Table 4, figure 2).
Of all 243 cases of prostate cancer, 93 patients underwent robotic radical prostatectomy. We compared the biopsy histology to prostatectomy histology and found 25 cases of upgraded histology. (According to AJCC 8th edition histologic grade group). And we compared the NLR in these two groups of patients; there was no statistically significant different. (Table 5)
Previous articles had described the association of NLR and localized prostate cancer. Raised NLR was associated with higher incidence of prostate cancer. Kawahara’s paper  first demonstrated NLR was significantly higher in localized prostate cancer patients. Total 810 patients who underwent TRUS biopsy with PSA 4-10 ng/ml were included in this study. Results revealed NLR was significantly higher in prostate cancer group compared to benign group. Conversely, Huang TB et al  analyzed 662 patients who underwent TRUS biopsy with valid CBC before biopsy. They found out there was no significant difference of NLR in benign and prostate cancer group; however in the subgroup analysis of patients of PSA 4-10, NLR was significantly higher in prostate cancer group. And there were other similar studies to support this conclusion. [7,8] Other studies also reported that NLR might be helpful to predict TRUS biopsy upgrading; help differentiate real Gleason > 7 cancer and stratifying low risk prostate cancer. [9-11]
On the contrary, Yuksel et al  studied 873 cases who underwent TRUS biopsy. They divided histology into benign prostatic hyperplasia (BPH), prostatitis and prostate cancer and found out there was no significant difference of NLR between cancer and BPH group.
Our study showed that there was no statistically significant difference of NLR value in patients with and without prostate cancer. Moreover, there was no significant difference in NLR ratio between patients with and without prostate cancer in the different PSA levels. These differences may be attributed to the intrinsic differences in the characteristics of each patient cohort in these studies. [Table 6, Figure 3-4]
To assess the cancer detection yield and proportion of clinical significant prostate cancer disease of current series; we used published reference in this field. There was 54.3% of high-grade cancer patients in current series which was significantly higher than 3 of the studies except for one. And in terms of cancer cases load: in this study 34.2% of patients with PSA 4-10 ng/ml were cancer cases which was not significantly lower than published data. In summary current series contained more clinical significant cancer and overall similar cancer yield which could not be accounted for negative results.
Other possible explanations for the different findings were probably related to the variation in the methodology:
- Standardized samples of CBC
In this study all CBC were done as pre-admission test. This would be strictly done within 4 weeks of biopsy. Also this would ensure patients were in generally well condition and no systemic infective disease which can affect NLR significantly. If we compare this to other studies, none of them mentioned the indication of CBC done before biopsy; neither the interval between CBC and biopsy were strictly controlled. Since NLR is not a specific biomarker and many medical conditions could alter the results if this was not strictly controlled.
- Methods of prostate biopsy All the previous publications regarding NLR in the diagnosis of prostate cancer were based on results of template TRUS biopsy. However non-targeted TRUS biopsy do have chance of missing cancer. Furthermore in articles that demonstrated positive predictive value of NLR; majority of the patients had PSA between 4-10 ng/L indicated relatively low disease burden and higher chance of getting a false negative biopsy.
Pal RP et al studied 426 patients who underwent both TRUS biopsy and mapping transperineal prostate biopsy . They found out that up to 53% (94/179) of patients who had benign histology on TRUS biopsy actually had prostate cancer that detected by mapping transperineal biopsy.
This study evaluated the feasibility of NLR in the diagnosis of prostate cancer via template transperineal biopsy. Due to low risk of urosepsis and accuracy of robotic biopsy we could take more template cores and this potentially may lead to lower cancer missing rate. The median number of cores taken was 29, which is significantly higher than traditional 10-16 cores TRUS biopsy. Furthermore this series included 73 patients with MRI targeted biopsy which had higher cancer detection rate (reference). From the data in table 6 we knew that overall cancer detection rate in this series was 34.2% which was higher than two of the published NLR series. [6,8]
In addition, the majority of the patients (73%) in this study already had previous negative biopsies which might further enhanced the reliability of the negative biopsies being the truly negatives.
- Risk stratification of prostate cancer
In our study majority of patients (94.2%) had clinically organ confined prostate cancer cT1-T2, 94.2%. Together with PSA < 10 ng/ml (133/243 54.7%) as well as Gleason 7 and below ( 210/243 86.4%) which might represent a relatively more indolent disease. This maybe one of the possibilities for negative results as NLR as a systemic biomarker maybe associated with more advanced disease. However none of the other NLR studies had mentioned clinical staging so direct comparison was not possible. Therefore, more prospective studies are required for further evaluation of the diagnostic and prognostic potential of NLR in prostate cancer.
To our knowledge this study was the first to evaluate NLR value in the diagnosis of prostate cancer in patients who underwent transperineal biopsy. We used RTPB, which was a consistent accurate way of doing prostate biopsy. And since the procedure was performed under general anaesthesia, all CBC were done as pre admission blood tests, which were more controlled and standardized. In addition, this was a consecutive series with a relatively large sample size.
There are limitations as a retrospective study. We excluded patients who did not have a valid PSA before biopsy, which might introduce selection bias. Although RTPB has relatively lower cancer missing rate; there is still chance of missing cancer in the biopsy. Large-scaled prospective study may be needed in this field.