Abstract
We propose a strategy to reduce unnecessary prostate biopsies in Chinese patients with total prostate-specific antigen (tPSA) >10 ng ml−1 and Prostate Imaging Reporting and Data System (PI-RADS) scores between 1 and 3. Clinical data derived from 517 patients of The First Affiliated Hospital of USTC (Hefei, China) from January 2020 to December 2023 who met the screening criteria for the study were retrospectively collected. Independent predictors were identified via univariate and multivariate logistic regression analysis. The diagnostic capacity of clinical variables was evaluated using the receiver operating characteristic (ROC) curves and area under the curve (AUC). A prostate biopsy strategy was developed via risk stratification. Of the 517 patients, 17/348 (4.9%) with PI-RADS 1–2 were diagnosed with clinically significant prostate cancer (csPCa), and 27/169 (16.0%) patients with PI-RADS 3 were diagnosed with csPCa. The appropriate prostate-specific antigen density (PSAD) cut-off values were 0.45 ng ml−2 for PI-RADS 1–2 patients and 0.3 ng ml−2 for PI-RADS 3 patients. The appropriate prostate volume (PV) cut-off values were 40 ml for PI-RADS 1–2 patients and 50 ml for PI-RADS 3 patients. The prostate biopsy strategy based on PSAD and PV developed in this study can reduce unnecessary prostate biopsies in patients with tPSA >10 ng ml−1 and PI-RADS 1–3. In the study, 66.5% (344/517) patients did not need to undergo prostate biopsy, at the expense of missing only 1.7% (6/344) patients with csPCa.
Keywords: clinically significant prostate cancer, overdiagnosis, prostate biopsy, risk stratification
INTRODUCTION
Prostate cancer (PCa) is the most frequently diagnosed cancer for men in 118 countries, according to the latest report.1 It is estimated that in 2022, the number of new cases in China will be 134 200, and the number of deaths will be 47 500.2 Primary screening for PCa currently relies on total prostate-specific antigen (tPSA), but the final diagnosis is still made via prostate biopsy.3,4 tPSA was reported having high sensitivity but low specificity, which leads to overdiagnosis in patients with abnormal tPSA.5 In China, patients with tPSA >10 ng ml−1 are advised to undergo prostate biopsy regardless of their free PSA/tPSA (f/tPSA) value, prostate-specific antigen density (PSAD), and the results of imaging.6 After analyzing 3007 patients who underwent prostate biopsies between 2003 and 2013, Mai et al.7 reported that the PCa detection rates were 47.9% (791/1651) in patients with tPSA >10 ng ml−1 and 36.7% (1039/2830) in patients with tPSA >4 ng ml−1. In a single-center study, the respective PCa detection rates were 52.2% (356/682) and 43.8% (417/952).8 In recent years, multiparametric magnetic resonance imaging (mpMRI) has become the recommended imaging examination to reduce overdiagnosis of PCa.9 Prostate Imaging Reporting and Data System (PI-RADS) score can help urologists determine whether patients should undergo prostate biopsy.10 In a meta-analysis of >3000 biopsy-naïve men, in patients with PI-RADS 1–2, the detection rates of clinically significant PCa (csPCa) were 3.6% (17/477) for PSAD <0.1 ng ml−2, 10.6% (51/482) for PSAD between 0.1 ng ml−2 and 0.2 ng ml−2, and 24.1% (28/116) for PSAD >0.2 ng ml−2. In patients with PI-RADS 3, the detection rates of csPCa were 8.9% (10/112) for PSAD <0.1 ng ml−2, 23.3% (51/219) for PSAD between 0.1 ng ml−2 and 0.2 ng ml−2, and 35.5% (27/76) for PSAD >0.2 ng ml−2.11 These detection rates have caused overdiagnosis and overtreatment. Gulati12 has proposed to reduce the overdiagnosis of PCa. The relationship between PI-RADS 1–3 lesions and csPCa is currently controversial, and there is no consensus on how to reduce unnecessary prostate biopsies.13 Few studies have focused specifically on patients with tPSA >10 ng ml−1 and PI-RADS 1–3. The aim of the current study was to develop a prostate biopsy strategy that can reduce overdiagnosis in Chinese patients with tPSA >10 ng ml−1 and PI-RADS 1–3.
PATIENTS AND METHODS
Patients and data collection
The study was approved by the Ethics Committee of The First Affiliated Hospital of USTC (Hefei, China; Approval No. 2024-RE-35). Clinical data derived from patients who had undergone prostate biopsy from January 2020 to December 2023 were retrospectively collected at the Department of Urology of The First Affiliated Hospital of USTC. The predetermined exclusion criteria were: (1) patients who had not been examined by magnetic resonance imaging (MRI) at our center; (2) patients with PI-RADS 4–5; (3) patients who had previously undergone prostate biopsy; (4) patients with tPSA ≤10 ng ml−1 or >100 ng ml−1; or (5) patients without complete clinical information (Supplementary Figure 1 (52.5KB, tif) ). Clinical data were obtained from the medical record system. All patients provided written informed consent before undergoing prostate biopsy.
MRI protocol
All patients were advised to undergo 3.0 T MRI (Trio Tim, Siemens Healthineers, Erlangen, Germany; and Discovery MR750W, GE Healthcare, Milwaukee, WI, USA) when tPSA was abnormal. The acquisition protocol included T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI). Apparent diffusion coefficient maps were generated via the diffusion-weighted imaging automatically (b values: 0, 800 s mm−2, and 1400 s mm−2). All images were interpreted by two radiologists with more than 5 years of experience in PCa. They devised a clear PI-RADS score according to the PI-RADS version 2.1 after reaching a consensus.10 Maximum anteroposterior diameter, longitudinal diameter, and transverse diameter were used to calculate prostate volume (PV).14
Prostate biopsy and pathological report
All patients underwent transperineal prostate biopsy guided by transrectal biplane ultrasound. A routine systematic 12-core prostate biopsy was conducted first. The 12 cores were symmetrically distributed bilaterally, from the apex of the prostate to the base, as far posterior and lateral as possible in the peripheral gland. Cognitive fusion targeted prostate biopsy was then performed if there were suspicious lesions on MRI. Professional pathologists graded the pathological results in accordance with the new grading system of the International Society of Urological Pathology.15 Given that it has little impact on health or life expectancy, low-grade PCa is internationally considered not to be a cancer.16 We no longer use low-grade PCa as an endpoint. csPCa (Gleason score ≥3 + 4) was the only endpoint in the current study.
Statistical analyses
Spearman’s rank correlation analysis was used to calculate correlational coefficients between clinical variables. Nonnormally distributed continuous variables were recorded as medians and interquartile ranges and compared via the Mann–Whitney U test. Categorical variables were recorded as numbers and percentages and compared using the Chi-square test. To identify independent predictors, both univariate and multivariate logistic regression analyses were performed. The diagnostic capacities of clinical variables were evaluated using receiver-operating characteristic (ROC) curves and the area under the curve (AUC). The De Long test was used to compare ROC curves.17 Statistical analysis was performed using the SPSS software (version 25.0; IBM, Armonk, NY, USA). ROC curves were plotted and compared via MedCalc (version 18.9.1; MedCalc Software, Ostend, Belgium). P < 0.05 was considered statistically significant.
RESULTS
Clinical and pathological characteristics
Clinical data were collected from 517 patients, including 348 patients with PI-RADS 1–2 and 169 patients with PI-RADS 3. In the PI-RADS 1–2 group, 17 patients were diagnosed with csPCa, and 331 patients were diagnosed with clinically insignificant PCa (cisPCa) or non-PCa. In the PI-RADS 3 group, 27 patients were diagnosed with csPCa, and 142 patients were diagnosed with cisPCa or non-PCa. Age, body mass index (BMI), tPSA, PV, and PSAD data are shown in Table 1. In the comparison of clinical variables in the csPCa, cisPCa, and non-PCa groups based on different PI-RADS scores, only PV and PSAD exhibited statistically significant differences (all P < 0.001).
Table 1.
Demographic data of all qualified patients
| Variable | PI-RADS 1–3 (all patients) | PI-RADS 1–2 | PI-RADS 3 | aP | bP | ||
|---|---|---|---|---|---|---|---|
|
|
|
||||||
| cisPCa and non-PCa | csPCa | cisPCa and non-PCa | csPCa | ||||
| Patient (n) | 517 | 331 | 17 | 142 | 27 | ||
| Age (year), median (IQR) | 69.0 (62.0–74.0) | 68.0 (61.5–74.0) | 67.0 (65.0–74.0) | 69.0 (64.3–74.0) | 71.0 (64.5–77.5) | 0.901 | 0.206 |
| BMI (kg m−2), median (IQR) | 23.70 (21.80–25.47) | 23.83 (22.10–25.71) | 23.14 (20.40–25.60) | 23.27 (21.49–25.08) | 23.53 (21.44–25.25) | 0.399 | 0.825 |
| tPSA (ng ml−1), median (IQR) | 15.64 (12.45–21.56) | 15.20 (12.22–20.33) | 17.30 (15.63–22.39) | 17.08 (12.92–22.06) | 20.38 (12.86–34.57) | 0.119 | 0.134 |
| PV (ml), median (IQR) | 61.50 (40.77–86.18) | 63.50 (42.08–90.55) | 33.42 (25.45–50.34) | 62.43 (44.01–84.33) | 38.55 (28.13–47.33) | <0.001 | <0.001 |
| PSAD (ng ml−2), median (IQR) | 0.28 (0.19–0.45) | 0.26 (0.17–0.41) | 0.64 (0.49–0.87) | 0.28 (0.21–0.44) | 0.57 (0.34–0.96) | <0.001 | <0.001 |
aComparison between cisPCa and non-PCa group and csPCa group for patients with PI-RADS 1–2. bComparison between cisPCa and non-PCa group and csPCa group for patients with PI-RADS 3. PI-RADS: Prostate Imaging Reporting and Data System; BMI: body mass index; tPSA: total prostate-specific antigen; PV: prostate volume; PSAD: prostate-specific antigen density; csPCa: clinically significant prostate cancer; IQR: interquartile range; cisPCa: clinically insignificant prostate cancer
Determination of independent predictors
Spearman’s rank correlations between PSAD, PV, and tPSA were calculated prior to logistic regression analysis, to reduce confounding (Supplementary Figure 2 (81.2KB, tif) ). PSAD was significantly correlated with tPSA (P < 0.001, r = 0.466) and PV (P < 0.001, r = −0.740). In univariate logistic regression analysis, tPSA (P = 0.003, odds ratio [OR]: 1.026, 95% confidence interval [CI]: 1.009–1.043), PV (P < 0.001, OR: 0.954, 95% CI: 0.937–0.971), PSAD (P < 0.001, OR: 5.717, 95% CI: 3.069–10.650), and PI-RADS score (P < 0.001, OR: 3.702, 95% CI: 1.956–7.006) were significant predictors of csPCa when all patients were analyzed as a single group. Based on the results of Spearman’s rank correlation analyses, tPSA and PV were not included in the multivariate logistical regression analysis to reduce confounding. In multivariate logistic regression analysis, PSAD (P < 0.001, OR: 6.016, 95% CI: 3.118–11.607) and PI-RADS score (P < 0.001, OR: 3.693, 95% CI: 1.860–7.333) were independent predictors of csPCa when all patients were analyzed as a single group (Table 2).
Table 2.
Determining the independent predictors of clinically significant prostate cancer by univariate and multivariate analysis for all patients
| Clinical variable | Univariate analysis | Multivariate analysis | ||||
|---|---|---|---|---|---|---|
|
|
|
|||||
| OR | 95% CI | P | OR | 95% CI | P | |
| Age | 1.028 | 0.991–1.066 | 0.140 | |||
| BMI | 0.969 | 0.869–1.080 | 0.570 | |||
| tPSA | 1.026 | 1.009–1.043 | 0.003 | |||
| PV | 0.954 | 0.937–0.971 | <0.001 | |||
| PSAD | 5.717 | 3.069–10.650 | <0.001 | 6.016 | 3.118–11.607 | <0.001 |
| PI-RADS score | 3.702 | 1.956–7.006 | <0.001 | 3.693 | 1.860–7.333 | <0.001 |
PI-RADS: Prostate Imaging Reporting and Data System; BMI: body mass index; tPSA: total prostate-specific antigen; PV: prostate volume; PSAD: prostate-specific antigen density; 95% CI: 95% confidence interval; OR: odds ratio
Diagnostic capacity of clinical variables
In order to evaluate the diagnostic capacities of clinical variables with respect to csPCa, ROC curves were plotted and AUCs were compared (Figure 1a). PSAD (AUC: 0.806, 95% CI: 0.769–0.839) and PV (AUC: 0.794, 95% CI: 0.756–0.828) exhibited the best diagnostic capacities, followed by tPSA (AUC: 0.611, 95% CI: 0.567–0.653), age (AUC: 0.553, 95% CI: 0.509–0.597), and BMI (AUC: 0.531, 95% CI: 0.487–0.575). ROC curves were plotted for groups with different PI-RADS scores (Figure 1b and 1c). In PI-RADS 1–2 patients, the respective AUC values for PSAD and PV were 0.843 and 0.789, respectively, which were higher than those for tPSA, BMI, and age. Similarly, in PI-RADS 3 patients, the diagnostic capacities of PSAD (AUC: 0.775, 95% CI: 0.704–0.835) and PV (AUC: 0.808, 95% CI: 0.740–0.864) were better than those of other variables. The above results indicated that PSAD and PV had the best diagnostic capacities, both in all patients as a collective group, and in subgroups of patients with different PI-RADS scores (Table 3).
Figure 1.
csPCa diagnostic capacity of clinical variables. (a) ROC curves for the diagnosis of csPCa for all patients. ROC curves for the diagnosis of csPCa for (b) PI-RADS 1–2 patients and (c) PI-RADS 3 patients. BMI: body mass index; csPCa: clinically significant prostate cancer; PSAD: prostate-specific antigen density; PV: prostate volume; tPSA: total prostate-specific antigen; PI-RADS: Prostate Imaging Reporting and Data System.
Table 3.
Diagnostic performance of the clinical variables for clinically significant prostate cancer
| Clinical variable | AUC | 95% CI | Sensitivity (%) | Specificity (%) | P |
|---|---|---|---|---|---|
| PI-RADS 1–2 | |||||
| Age | 0.509 | 0.455–0.563 | 88.24 | 25.08 | Reference |
| BMI | 0.561 | 0.507–0.614 | 41.18 | 83.69 | 0.624 |
| tPSA | 0.612 | 0.559–0.663 | 76.47 | 54.08 | 0.166 |
| PV | 0.789 | 0.742–0.830 | 88.24 | 61.03 | 0.005 |
| PSAD | 0.843 | 0.801–0.880 | 88.24 | 80.06 | <0.001 |
| PI-RADS 3 | |||||
| Age | 0.577 | 0.499–0.652 | 33.33 | 83.80 | Reference |
| BMI | 0.513 | 0.435–0.591 | 77.78 | 11.27 | 0.437 |
| tPSA | 0.591 | 0.513–0.666 | 44.44 | 78.87 | 0.847 |
| PV | 0.808 | 0.740–0.864 | 85.19 | 68.31 | 0.004 |
| PSAD | 0.775 | 0.704–0.835 | 85.19 | 59.15 | 0.009 |
| All patients | |||||
| Age | 0.553 | 0.509–0.597 | 97.73 | 12.05 | Reference |
| BMI | 0.531 | 0.487–0.575 | 27.27 | 87.74 | 0.761 |
| tPSA | 0.611 | 0.567–0.653 | 72.73 | 48.63 | 0.270 |
| PV | 0.794 | 0.756–0.828 | 84.09 | 65.12 | <0.001 |
| PSAD | 0.806 | 0.769–0.839 | 77.27 | 73.36 | <0.001 |
PI-RADS: Prostate Imaging Reporting and Data System; BMI: body mass index; tPSA: total prostate-specific antigen; PV: prostate volume; PSAD: prostate-specific antigen density; AUC: area under curve; 95% CI: 95% confidence interval
Grouping patients by cut-off values
PSAD and PV cut-off values were mainly determined via Youden’s index. Considering the actual demand, the final cut-off values were taken as adjacent integers, respectively (Supplementary Table 1). First, all PI-RADS 1–2 patients were divided into two groups with PSAD of 0.45 ng ml−2 as the cut-off value. Only 3/270 (1.1%) patients were diagnosed with csPCa in the PSAD ≤0.45 ng ml−2 group (Group 3). Second, patients with PSAD >0.45 ng ml−2 were further divided with PV of 40 ml as the cut-off value. In that analysis, 11/49 (22.4%) patients were diagnosed with csPCa in the PSAD >0.45 ng ml−2 and PV ≤40 ml group (Group 1). The detection rate of csPCa was 3/29 (10.3%) in the PSAD >0.45 ng ml−2 and PV >40 ml group (Group 2).
All PI-RADS 3 patients were divided into three groups based on cut-off value of 0.3 ng ml−2 for PSAD and 50 ml for PV. In that analysis, 21/56 (37.5%) patients with PSAD >0.3 ng ml−2 and PV ≤ 50 ml were diagnosed with csPCa (Group 4). The detection rate of csPCa was only 3/74 (4.1%) in patients with PSAD ≤0.3 ng ml−2 and PV >50 ml (Group 6). Three (7.7%) of the remaining 39 patients were diagnosed with csPCa (Group 5), as shown in Figure 2a.
Figure 2.
Distribution of patients in different groups, grouping scheme, and prostate biopsy strategy. (a) Frequency distributions in different groups by PV and PSAD cut-off values. (b) Prostate biopsy strategy for use in PI-RADS 1–3 patients with tPSA >10 ng ml−1. Group 1: patients with PSAD >0.45 ng ml−2 and PV ≤40 ml; Group 2: patients with PSAD >0.45 ng ml−2 and PV >40 ml; Group 3: patients with PSAD ≤0.45 ng ml−2; Group 4: patients with PSAD >0.3 ng ml−2 and PV ≤50 ml; Group 5: patients with PSAD >0.3 ng ml−2 and PV >50 ml; PSAD ≤0.3 ng ml−2 and PV ≤50 ml; Group 6: patients with PSAD ≤0.3 ng ml−2 and PV >50 ml. csPCa: clinically significant prostate cancer; PI-RADS: Prostate Imaging Reporting and Data System; PSAD: prostate-specific antigen density; PV: prostate volume; tPSA: total prostate-specific antigen.
Prostate biopsy strategy
A new prostate biopsy strategy was developed for application in patients with tPSA >10 ng ml−1 and PI-RADS 1–3 to reduce unnecessary prostate biopsies. When developing the strategy, the risk stratification of biopsy decisions in the latest guidelines on PCa was referred to. Prostate biopsy should be recommended for cancer risks over 30%, highly considered for risks of 20%–30%, considered for risks of 10%–20%, and not recommended for risks under 10%.3 In the current study cohort, prostate biopsy would be recommended for PI-RADS 3 patients with PSAD >0.3 ng ml−2 and PV ≤50 ml but not for PI-RADS 1–2 patients with PSAD ≤0.45 ng ml−2 or PI-RADS 3 patients with PSAD ≤0.3 ng ml−2 and PV >50 ml. In PI-RADS 1–2 patients, prostate biopsy should be highly considered when PSAD >0.45 ng ml−2 and PV ≤40 ml. Notably, although the cancer risk was only 6.7% in PI-RADS 3 patients in the PSAD >0.3 ng ml−2 and PV >50 ml group, we still recommend that such patients consider undergoing prostate biopsy. Other patients should decide whether to undergo prostate biopsy or not based on the actual situation. A diagram of the prostate biopsy strategy developed in the study is shown in Figure 2b.
DISCUSSION
Whether tPSA screening can reduce PCa mortality has historically been controversial.18,19 It has recently been reported that the number of deaths from PCa can be reduced by PSA screening at a median of 15-year follow-up based on the secondary analysis.20 tPSA screening does improve the diagnosis of PCa, particularly with respect to increases in tPSA. Digital rectal examination (DRE) has a limited role in current PCa screening in the era of mpMRI. Results of a meta-analysis that included seven studies with a total of 9241 patients indicated an overall sensitivity of 0.51 and an overall specificity of 0.59 when DRE was used for PCa diagnosis.21 Urologists increasingly favor PI-RADS score grading. However, it has been clearly recommended that patients undergo prostate biopsy if tPSA is >10 ng ml−1, in accordance with the Chinese guideline.4 Moreover, the combination of tPSA levels of 4–10 ng ml−1 and PI-RADS 3 is referred to as the double gray zone, and PI-RADS 1–2 patients are usually not advised to undergo prostate biopsy.10,22 In China, PI-RADS 1–3 patients with tPSA levels of 4–10 ng ml−1 are advised to undergo regular examinations rather than prostate biopsy. Data from the Chinese Prostate Cancer Consortium showed that the incidence of csPCa was only 11% in Chinese patients with tPSA levels of 4–10 ng ml−1.23 Even if patients with tPSA levels of 4–10 ng ml−1 and PI-RADS 1–3 choose to undergo prostate biopsy, we believe the detection rate of csPCa will be below 11%. Interestingly, Hansen et al.24 found a significant difference between the increase in tPSA (4–10 ng ml−1 vs >10 ng ml−1) and the detection rate of csPCa in PI-RADS 4–5 patients, but not in PI-RADS 1–3 patients. In PI-RADS 1–3 patients in the current study, there were also no differences in tPSA with respect to detection rates of csPCa, cisPCa, and non-PCa. The traditional strategy led to overdiagnosis in 331/348 (95.1%) patients with PI-RADS 1–2 and 142/169 (84.0%) patients with PI-RADS 3.
The detection rate of csPCa in the present study was lower than those reported in Western cohorts, and this is probably due to several reasons. The characteristics of PCa in Chinese patients differ from those in Western patients, with Chinese patients having higher tPSA and PSAD. For example, Chen et al.23 reported that compared with Western cohorts, the detection rates of PCa and csPCa were lower in the Chinese cohort at any given tPSA level. Among them, the incidence of PCa was 15% lower than Western cohorts for patients with tPSA levels of 4–10 ng ml−1. In a multicenter retrospective study in a collective Chinese cohort, sensitivity was 0.70 and specificity was 0.85 when PSAD >0.61 ng ml−2 was used for the diagnosis of PCa.25 Other studies indicate that the incidence of PCa varies greatly in different continents, and Asia is traditionally considered as a low-incidence area.26 These studies suggest that appropriate increases in tPSA and/or PSAD cut-off values will improve the detection rate of PCa. The reason for the differential incidence rate could be that China has a large population and there are large disparities in medical conditions in China, particularly in many poor rural areas where patients do not have regular routine medical checkups. As a result, some patients have already progressed to the middle to late stages of PCa in the clinic and therefore have higher tPSA and PSAD levels. Unnecessary prostate biopsy will encumber patients with an economic burden and postoperative complications such as infection.27,28 Prostate biopsy strategies in PI-RDAS 4–5 patients have continuously been proposed. Numerous studies have shown that in patients with higher PI-RADS and PSAD values, strategies that consider the combination of both can reduce unnecessary prostate biopsies.29 However, few prostate biopsy strategies have been proposed for use in Chinese PI-RADS 1–3 patients with tPSA >10 ng ml−1. Therefore, herein we propose a prostate biopsy strategy that is more suitable for use in Chinese patients.
PSAD and PV are two common indexes in urology departments. PSAD is positively correlated with PCa positivity, whereas the opposite is true of PV.11,30 Under current conditions, it makes sense to incorporate these two commonly used variables into a strategy to reduce unnecessary prostate biopsies. In the current study, PSAD and PV were used to group all patients, then a biopsy strategy was proposed based on the risk of csPCa. Only 1.1% (3/270) PI-RADS 1–2 patients were diagnosed with csPCa when PSAD was ≤0.45 ng ml−2, indicating that 267 patients had undergone unnecessary prostate biopsies. There are also reports that PI-RADS 1–2 patients can be grouped based on different PSAD cut-off values to reduce overdiagnosis.29 However, these studies are not specific to patients with tPSA >10 ng ml−1. We also regrouped patients based on PV cut-off values because 14 patients with PSAD >0.45 ng ml−2 were still diagnosed with csPCa. The risk stratification of these patients and formulation of a prostate biopsy strategy can help urologists to make biopsy decisions. Such decisions have been in dispute in PI-RADS 3 patients, and no agreement has been reached.10 In the current study, the csPCa detection rate was 27/169 (16.0%) in PI-RADS 3 patients with tPSA >10 ng ml−1, and 53/169 (31.4%) were diagnosed with PCa (Gleason score ≥3 + 3). cisPCa accounted for almost half of those patients. The csPCa detection rate is only approximately 4.1% in patients with PSAD ≤0.3 ng ml−2 and PV >50 ml. In contrast, 37.5% (21/56) of patients with PSAD >0.3 ng ml−2 and PV ≤50 ml were diagnosed with csPCa. Urologists can clearly determine whether a patient needs to undergo prostate biopsy using the strategy proposed herein, negating ambiguity. Notably, although we did not compare our cohort with the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators, the risk of PCa and high-grade disease was overestimated by approximately 20% in a Chinese cohort when the ERSPC risk calculators were applied.31 Lesion size was more strongly correlated with Gleason scores in PI-RADS 4–5 patients.32 Other potential indicators such as the prostate health index and prostate-specific membrane antigen positron emission tomography/magnetic resonance will also improve the possibility of reducing prostate biopsies in PI-RADS 3 patients.33,34 High-quality, prospective, multicenter studies in PI-RADS 3 patients with tPSA >10 ng ml−1 are necessary in the future.
The current study had some limitations. It was a single-center retrospective study, and the sample size was not very large. The PSAD cut-off value used in the study was higher than other center; thus, further validation is needed in other cohorts. DRE results were not fully recorded and PI-RADS scores were 1–2 for most patients, negating direct comparisons with ERSPC plus mpMRI risk calculators. Patients with tPSA levels between 4 ng ml−1 and 10 ng ml−1 were not included in the study. Finally, the prostate biopsies were performed independently by two urologists, and their experience will inevitably have affected the biopsy results.
CONCLUSIONS
In this retrospective study, we developed a prostate biopsy decision strategy based on PSAD and PV in Chinese PI-RADS 1–3 patients with tPSA >10 ng ml−1, to reduce unnecessary prostate biopsies. Of 517 patients, 344 (66.5%) did not need to undergo prostate biopsy, at the expense of missing 1.7% (6/344) patients with csPCa.
AUTHOR CONTRIBUTIONS
JX and CMW designed the study and reviewed the final version of the manuscript. XFF and XY collected the clinical data. YHC, YFM, and TZ completed data analysis and charting. QFD and YXL wrote the initial manuscript. All authors read and approved the final manuscript.
COMPETING INTERESTS
All authors declare no competing interests.
Study flowchart of this study. tPSA, total prostate-specific antigen; MRI: magnetic resonance imaging; PI-RADS, prostate imaging reporting and data system.
Spearman’s rank correlation analysis for PSAD, PV, and tPSA. (a) Spearman’s rank correlation analysis for PSAD and tPSA. (b) Spearman’s rank correlation analysis for PSAD and PV. (c) Spearman’s rank correlation analysis for PV and tPSA. tPSA, total prostate-specific antigen; PV, prostate volume; PSAD, prostate -specific antigen density.
ACKNOWLEDGMENTS
This study was partly supported by the National Natural Science Foundation of China (No. 82072807), the Scientific Research Project of Universities of the Department of Education of Anhui Province (No. 2022AH040182), and the Anhui Province Key Clinical Specialties Construction Project (2023). We sincerely appreciate assistance from Medical Research Center of Anhui Provincial Hospital (Hefei, China) in providing convenient conditions.
Supplementary Information is linked to the online version of the paper on the Asian Journal of Andrology website.
SUPPLEMENTARY INFORMATION
THE METHOD FOR DETERMINING THE CUT-OFF VALUES
In the study, the initial cut-off values were determined by the Youden's index. The initial cut-off values of PASD and PV were 0.443 ng ml-2 and 39.75 ml for patients with PI-RADS 1–2, 0.311 ng ml-2, and 51.92 ml for patients with PI-RADS 3. Considering the clinical practice, we chose the final values of PSAD and PV were 0.45 ng ml-2 and 40 ml for patients with PI-RADS 1–2, 0.3 ng ml-2, and 50 ml for patients with PI-RADS 3. Moreover, we also calculated the sensitivity and specificity corresponding to different cut-off values (Supplementary Table 1).
Supplementary Table 1.
Sensitivity and specificity of different cut-off values in the diagnosis of clinically significant prostate cancer
| PI-RADS | Cut off values | Grouping scheme | For csPCa | ||
|---|---|---|---|---|---|
|
| |||||
| Sensitivity (%) | Specificity (%) | Risk (%) | |||
| 1–2 | Initial cut-off values | PSAD >0.443 ng ml−2 and PV ≤39.75 ml | 73.3 | 40.9 | 22.0 |
| Finial cut-off values | PSAD >0.45 ng ml−2 and PV ≤40 ml | 78.6 | 40.6 | 22.5 | |
| 3 | Initial cut-off values | PSAD >0.311 ng ml−2 and PV ≤51.92 ml | 77.8 | 76.1 | 38.2 |
| Finial cut-off values | PSAD >0.3 ng ml−2 and PV ≤50 ml | 77.8 | 75.4 | 37.5 | |
csPCa: clinically significant prostate cancer; PV: prostate volume; PSAD: prostate-specific antigen density; PI-RADS: prostate imaging reporting and data system
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Study flowchart of this study. tPSA, total prostate-specific antigen; MRI: magnetic resonance imaging; PI-RADS, prostate imaging reporting and data system.
Spearman’s rank correlation analysis for PSAD, PV, and tPSA. (a) Spearman’s rank correlation analysis for PSAD and tPSA. (b) Spearman’s rank correlation analysis for PSAD and PV. (c) Spearman’s rank correlation analysis for PV and tPSA. tPSA, total prostate-specific antigen; PV, prostate volume; PSAD, prostate -specific antigen density.