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Abstract

The aim of the study was to analyze population-based prostate cancer (PCa) screening and the incidence of PCa among males ≥50 years of age residing in the Luqiao district of Taizhou, China. From October to December 2020, male residents ≥50 years of age were screened for serum total prostate-specific antigen (total-PSA). If t-PSA re-test levels persisted above 4 μg/L, subjects underwent further noninvasive examinations, including digital rectal examination or multiparameter magnetic resonance imaging (mpMRI) of the prostate. Subjects underwent prostate biopsy of pathological tissue based on t-PSA and mpMRI results. A total of 3524 (49.1%) residents participated in this PCa screening study. In total, 285 (8.1%) subjects exhibited t-PSA levels ≥4.0 μg/L and 112 (3.2%) underwent noninvasive examinations. Forty-two (1.2%) residents underwent prostate biopsy, of which 16 (0.45%) were diagnosed with PCa. Of those diagnosed with PCa, three (19%) had localized PCa (cT1-cT2N0M0), six (37%) had locally advanced PCa (cT3a- cT4N0-1M0), and seven (44%) had advanced metastatic PCa (M1). Unfortunately, 3477 (48.5%) residents did not participate in the study, mainly due to lack of awareness of PCa based on feedback from local health centers. Age and t-PSA were used as primary screening indicators and, when further combined with mpMRI and prostate biopsy, confirmed the diagnosis of PCa among participating residents. Although this was a relatively economical and convenient screening method, education and knowledge should be further enhanced to increase the participation rate in PCa screening programs.

Keywords

early prostate cancer screening Taizhou magnetic resonance imaging prostate-specific antigen prostate puncture

Introduction

Prostate cancer (PCa) is one of the most common malignant tumors among elderly males in China. In 2015, the national tumor incidence report revealed that the incidence of PCa among Chinese males reached 10.23/100,000 population and the mortality rate was 4.36/100,000 and, moreover, that its incidence was increasing (Fu et al., 2020). Some studies and surveys have reported that two thirds of PCa patients in China are in the advanced stages of disease at the time of consultation, and the incidence of PCa is increasing over time (Fu et al., 2020; Liu et al., 2019). The survival of patients with PCa is influenced by many factors. The 5-year relative survival rate of patients with limited PCa or with only regional spread of PCa was up to 100%; however, the 5-year survival rate among those with distant metastases was only 29.3% (Ma et al., 2008). There is no established model for PCa screening in China. A meta-analysis revealed that a cut-off value of >4 μg/L for prostate-specific antigen (PSA) for detecting PCa in the Chinese population has high sensitivity but low specificity, and that PCa screening should be further based on PSA levels (B. H. Wang et al., 2020). To this end, we used age and total-PSA (t-PSA) as the main indicators to conduct PCa screening among local male residents of Luqiao, Taizhou, China. The aim was to investigate population-based PCa screening and to analyze the incidence of PCa among male residents ≥50 years of age.

Method

Study Population

The present study included 7173 males ≥50 years of age who resided in the Zhejiang province, China (Figure 1). The protocol was supported by the government (Taizhou Luqiao District Health Committee) and approved by the Ethics Committee of Taizhou Hospital (NO. K20210402). Included subjects were asked to sign an informed consent before undergoing serum t-PSA testing. Considering that t-PSA screening may result in medical overdiagnosis and overtreatment, the risks and benefits of prostate screening were detailed in the informed consent form, in accordance with the requirements of Consensus of Chinese Experts on Prostate Cancer Screening (Prostate Cancer Working Group of Genitourinary Cancer Committee in Chinese Anti-Cancer Association, 2017) at the beginning of the study.

Figure 1.

Presentation of PCa Screening Data in This Study

Study Protocol

Exclusion Criteria

Serum t-PSA levels are influenced by many factors, including enlarged prostate volume, lower urinary tract symptoms, acute urinary retention, medications, and prostate inflammation. Taking into account the consensus of experts and the experience of published studies (Bernal-Soriano et al., 2019; Merriel et al., 2018; Palsdottir et al., 2019; Prostate Cancer Working Group of Genitourinary Cancer Committee in Chinese Anti-Cancer Association, 2017), several exclusion criteria were defined, including poor health and life expectancy <10 years, use of 5-alpha-reductase inhibitors within the previous 6 months, recent urinary tract infections or urological procedures, acute urinary retention, and acute or chronic bacterial or nonbacterial prostatitis within the past 6 weeks. Ultimately, 172 subjects were excluded from the study.

Screening Process for PCa

First, the local government counted the number of eligible male residents ≥50 years of age and sent the statistics to the local health centers. Second, subjects included in this study were scheduled to be screened at the local health center. Third, each subject underwent a serum t-PSA test, and name, age, contact information, urinary history, and relevant family history were recorded. Primary care physicians would be required to administer counseling and answer questions. Fourth, information from each resident was kept confidential and the result of serum testing was sent individually by mail to the subject or family members. Finally, the team maintained contact with the directors of health centers through “WeChat” or telephone. For subjects with t-PSA levels ≥4 μg/L, the director informed them of further examination within 1 week (Figure 2).

Figure 2.

Flowchart of Prostate Cancer Screening

Serum t-PSA Protocol

Blood samples were tested according to protocol in the clinical laboratory of the authors’ medical center. The immunoassay instrument and assay kit used for testing were acquired from Beckman Coulter (Brea, CA, USA), and operation of the instrument was performed by trained personnel in strict accordance with manufacturer’s instructions.

Noninvasive Examination

Digital rectal examination is a simple and effective method and has been widely used in clinical practice and, moreover, in combination with PSA, can improve the detection rate of early PCa (Ilic et al., 2013). Because PSA levels can be affected by digital rectal examination, only residents with t-PSA levels ≥4 μg/L underwent palpation of the prostate in this screening at the beginning of the study. The specificity of ultrasound or computed tomography (CT) examination for the early diagnosis of PCa is not high (De Visschere et al., 2010; Klotz et al., 2021). Ultrasound and CT were mainly used to rule out other comorbid diseases such as bladder stones, urethral stones, and bladder tumors. It has been reported that multiparameter magnetic resonance imaging (mpMRI) and the prostate imaging reporting and data system (PI-RADS) can be used to localize, diagnose, and assess the risk for PCa, and has an important role in clinical practice (Ahmed et al., 2017; Hötker & Donati, 2021; Weinreb et al., 2016). PI-RADS (Version 2) score mainly referred to the quantitative evaluation of prostate magnetic resonance imaging (MRI) after comparison of different parameters and comprehensive analysis. According to PI-RADS, each patient was scored with a total score of 5 points. When the score was 1 or 2, the patient was less likely to have prostate cancer, whereas when the score ≥ 3, the patient might have prostate cancer. A PI-RADS score ≥3 was used as the cut-off value. Enrolled residents were required to undergo 3.0 Tesla mpMRI of the prostate before prostate biopsy.

Transperineal Biopsy of the Prostate

Although transperineal prostate biopsy did not require intestinal cleaning and had relatively few complications, it required linear rectal probe or biplanar probe, and had high requirements for operator experience. At present, transrectal ultrasound-guided (TRUS) transperineal biopsy has become the main development trend of prostate biopsy. Subjects who agreed to undergo invasive examination underwent systematic perineal puncture (12 needles) performed by a senior urologist. Prostate biopsies of subjects were performed under local anesthesia and the same puncture needle was used intraoperatively.

TNM Staging and Pathological Grading

According to TNM staging, cT1 ~ cT2N0M0 was limited PCa, cT3a ~ cT4N0 ~1M0 was locally advanced PCa, and M1 was advanced metastatic PCa. Pathology was graded and grouped according to the World Health Organization/International Society of Urological Pathology system. Limited PCa was classified as low, intermediate, and high risk according to D’Amico risk stratification.

Treatment and Follow-Up

Treatment options for PCa included close observation, surgery, drugs, and radiation. Patients diagnosed with PCa were followed up for 1 year.

Statistical Analysis

Measurement data are expressed as median (range) and count data are expressed as percentage.

Results

Subject Characteristics

From October to December 2020, 3,524 (49.1%) male subjects participated in the present screening study. The median age of the 3,524 subjects screened was 65 (range = 50–83) years; Figure 3), with subjects distributed across age groups as follows: 50 to 59 (n = 759 [21.5%]), 60 to 69 (n = 2,029 [57.5%]), 70 to 79 (n = 637 [18.1%]), and ≥80 years (n = 63 [1.9%]). Median (range) t-PSA levels among these age groups were as follows: 1.47 μg/L (0.11–57.6 μg/L), 2.01 μg/L (0.16–121.3 μg/L), 1.94 μg/L (0.23–115.8 μg/L), and 2.3 μg/L (0.7–216.6 μg/L), respectively (Table 1). In total, 3,477 (48.5%) residents did not provide informed consent and, as such, did not participate in this study. The directors of each health center communicated with these 3,477 residents by telephone and summarized the major reasons for nonparticipation (Table 2).

Figure 3.

Age Distribution of the Residents Who Participated in the Screening

Table 1.

Age-Related Distribution of the Serum t-PSA Level in the 3,524 Male Residents

Age (Y)	n	Median serum t-PSA (μg/L)
50–59	795	1.47 [0.11~57.6]
60–69	2029	2.01 [0.16~86.3]
70–79	637	1.94 [0.23~115.8]
≥ 80	63	2.3 [0.7~216.6]

Note. t-PSA = total prostate-specific antigen.

Table 2.

Major Reasons of 3477 Residents Who Did Not Participate in Screening

List of reasons	N = 3,477
Residents did not have any knowledge about the prostate cancer.	1,750 (50%)
Residents could not get timely professional answers at the scene.	356 (10%)
Residents did not have any discomfort and were reluctant to participate in the screening.	655 (19%)
Residents showed little interest to the screening.	263 (8%)
Residents’ work schedules conflicted with the screening.	167 (5%)
Residents had fear and concern about the prostate cancer.	144 (4%)
Primary care physicians were unabled to contact residents.	97 (3%)
Other reasons.	45 (1%)

PCa Screening Results

Of the 3,524 subjects included in the study, 285 (8.1%) had t-PSA levels ≥4.0 μg/L and 112 (3.2%) underwent noninvasive examination. Sixty-two (1.8%) subjects with t-PSA levels between 4 and 10 μg/L and PI-RADS scores <3 were referred to follow-up. Forty-two (1.2%) subjects underwent prostate biopsy and 16 (0.45%) had a confirmed diagnosis of PCa. The 42 subjects had no postoperative fever, urinary frequency, or urinary urgency after prostate biopsy; however, 35 experienced postoperative hematuria, which improved after observation or administration of finasteride. Eight (0.2%) subjects refused to undergo prostate biopsy, among whom five (0.01%) feared complications associated with puncture such as bleeding, pain, infection, long hospitalization, and/or financial constraints. The remaining three (0.08%) subjects had doubted the results of the noninvasive examination and visited a higher level hospital for further consultation at that time. Nevertheless, contact has been maintained with these patients.

Characteristics of Subjects With Confirmed PCa

Pathological data were available for all 16 patients diagnosed with PCa (Table 3). The incidence of PCa in the 50 to 59, 60 to 69, 70 to 79, and ≥80 years’ age groups was 0.1% (1/795), 0.2% (4/2,029), 1.1% (7/637), and 6.3% (4/63), respectively. All pathological types were adenocarcinoma of the prostate. There were three (19%) cases of limited PCa (cT1 to cT2 N0 M0), six (37%) of locally advanced PCa (cT3aÿ§cT4 N0ÿ§1 M0), and seven (44%) of advanced metastatic PCa (M1) among patients with confirmed diagnosis. There was one (78%) case of low-risk and two (22%) cases of intermediate-risk in limited PCa.

Table 3.

Clinical Stages and Pathological Grades of PCa Confirmed in Different Age Groups of the 16 Males

Variable	Age (Y)				Total
Variable	50–59	60–69	70–79	≥80	Total
PCa confirmed (n)	1	4	7	4	16
Pathological pattern	Prostatic adenocarcinoma
T stage
T1~T2, n (%)	1 (100)	2 (50)	2 (29)	1 (25)	6 (38)
T3~T4, n (%)	0 (0)	2 (50)	5 (71)	3 (75)	10 (62)
N stage
N0, n (%)	1 (100)	3 (75)	7 (100)	4 (100)	15 (94)
N1, n (%)	0 (0)	1 (15)	0 (0)	0 (0)	1 (6)
M stage
M0, n (%)	1 (100)	3 (75)	5 (71)	0 (0)	9 (56)
M1, n (%)	0 (0)	1 (25)	2 (29)	4 (100)	7 (44)
WHO/ISUP grade
1, n (%)	1 (100)	0 (0)	0 (0)	0 (0)	1 (6)
2–3, n (%)	0 (0)	4 (100)	2 (29)	2 (50)	8 (50)
4–5, n (%)	0 (0)	0 (0)	5 (71)	2 (50)	7 (44)

Note. PCa = prostate cancer; WHO = World Health Organization; ISUP = International Society of Urological Pathology.

Combined with estimation of life expectancy, four (25%) residents with locally advanced PCa underwent laparoscopic radical prostatectomy and lymph node dissection. One (6%) subject with low-risk limited PCa underwent laparoscopic radical prostatectomy. Two (13%) subjects with intermediate-risk limited PCa underwent implantation of I-125 particles and endocrine therapy. Seven (44%) subjects with bone metastatic PCa were receiving zoledronic acid as an anti-bone metastatic therapy. Nine (56%) subjects underwent endocrine therapy, including the seven previously mentioned subjects who were currently undergoing treatment for bone metastases.

Outpatient Follow-Up in Patients Diagnosed With PCa

Patients who underwent surgery all had low PSA levels and did not experience severe urinary incontinence after 1 year of follow-up. Patients who underwent I-125 particle implantation and endocrine therapy also had low PSA levels after 1 year of follow-up. However, of patients with bone metastases, four developed metastatic castration-resistant PCa. These four patients had agreed to undergo new endocrine therapy or chemotherapy, with the latest PSA level <2 μg/L at follow-up. The remaining patients who underwent endocrine therapy alone or combination therapy all had low current PSA levels and had not developed metastatic castration-resistant PCa or non-metastatic castration-resistant PCa.

Discussion

Clinical Implications

PSA is a serine protease produced by prostate epithelial cells and is secreted directly into the prostatic ductal system. Because prostate tissue has a natural barrier to high levels of PSA, serum levels of PSA are normally very low (Rao et al., 2008). However, if prostate cells rupture, large amounts of PSA can enter the serum. Serum PSA exists in the form of free PSA (f-PSA) and t-PSA. Through a review of the literature addressing PCa screening, we found that the incidence of PCa varied over time, age, race, and screening methods (Table 4). A systematic review and meta-analysis of the accuracy of mpMRI for the diagnosis of PCa reported that the sensitivity and specificity of mpMRI were 0.87 (95% confidence interval [CI] = [0.81, 0.91]) and 0.68 (95% CI = [0.56, 0.79]; Zhen et al., 2019). In the present study, we initially used t-PSA and age as the primary screening indicators and mpMRI and prostate biopsy for subsequent screening, which reduced the need for blind prostate biopsy and enabled targeted observation of selected residents. Therefore, mpMRI represented an important auxiliary tool in PCa screening.

Table 4.

The Incidence of Prostate Cancer Varied With Different Time, Age, Race, and Screening Methods

Author (year)	Study design	Study period	Screened number	Screening age	t-PSA	Screening flowchart	Setting	Race	PCa overall incidence
Schröder et al. (2009)	Randomized controlled trial	1990–2006	182,000	50 ≤ age ≤ 74	t-PSA ≥ 4.0 ng/ml, t-PSA ≥ 3.0 ng/mL	t-PSA + DRE + biopsy	European	NA	Intervention group (8.2%)
Schröder et al. (2009)	Randomized controlled trial	1990–2006	182,000	50 ≤ age ≤ 74	t-PSA ≥ 4.0 ng/ml, t-PSA ≥ 3.0 ng/mL	t-PSA + DRE + biopsy	European	NA	Control group (4.8%)
Faria et al. (2010)	Cross-sectional study	2004–2007	17,571	Age ≥ 45	t-PSA ≥ 4.0 ng/mL	t-PSA + DRE + biopsy	Brazil	NA	3.70%
de Oliveira et al. (2021)	Cross-sectional study	2013	9,696	Age ≥ 40	t-PSA ≥ 4.0 ng/mL	t-PSA + DRE + biopsy	Brazil	White, Brown, Black, Yellow	2.60%
Martin et al. (2018)	Randomized controlled trial	2001–2016	Intervention group (189,386)	50 ≤ age ≤ 69	t-PSA ≥ 3.0 ng/mL	t-PSA + biopsy	United Kingdom	Non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic	Intervention group (4.3%)
Martin et al. (2018)	Randomized controlled trial	2001–2016	Control group (219,439)	50 ≤ age ≤ 69	Unscreened	Unscreened	United Kingdom		Control group (3.6%)
Andriole et al. (2012)	Randomized controlled trial	1993–2001	Intervention group (38,340)	NA	t-PSA ≥ 4.0 ng/mL	t-PSA + DRE + biopsy	United States	NA	Intervention group (1.08%)
Andriole et al. (2012)	Randomized controlled trial	1993–2001	Control group (38,345)	NA	t-PSA ≥ 4.0 ng/mL	t-PSA + DRE + biopsy	United States	NA	Control group (0.97%)
Patasius et al. (2020)	Randomized controlled trial	2006–2015	Intervention group (459,667)	45–49 with a family history of prostate cancer, 50 ≤ age ≤ 74	t-PSA ≥ 3.0 ng/mL	t-PSA + DRE + biopsy	Lithuania	NA	Intervention group (5.8%)
Patasius et al. (2020)	Randomized controlled trial	2006–2015	Control group (195,820)		t-PSA ≥ 3.0 ng/mL	t-PSA + DRE + biopsy	Lithuania	NA	Control group (0.7%)
Kitagawa et al. (2011)	Cross-sectional study	2000–2006	32,769	55 ≤ age ≤ 69	t-PSA ≥ 2.1 ng/mL	t-PSA + DRE + TRUS + biopsy	Kanazawa, Japan	Asian	0.76%
X. Wang et al. (2013)	Cross-sectional study	2010	2,862	50 ≤ age ≤ 69	t-PSA ≥ 4.0 ng/mL	t-PSA + biopsy	Beijing, China	Asian	1.36%
Liang et al. (2019)	Cross-sectional study	2018	6,903	Age ≥ 50	t-PSA ≥ 4.0 ng/mL	t-PSA-mpMRI-targeted biopsy	Nanjing, China	Asian	1.14%

Note. t-PSA = total prostate-specific antigen; PCa = prostate cancer; DRE = digital rectal examination; TRUS = transrectal ultrasound-guided; mpMRI = multiparameter magnetic resonance imaging.

Although the Taizhou and Nanjing areas are on the east coast of China, the PCa detection rate (0.45% [16/3,524]) in this study was different from previously reported results (1.14% [79/6,903]) of PCa screening by Liang and other Chinese investigators in Nanjing, China (Liang et al., 2019). Unfortunately, of the 16 residents who have been diagnosed, we also found one patient with pathologically confirmed intermediate-risk limited PCa between 50 and 59 years of age and one with advanced metastatic PCa between 60 and 69 years of age. This may also provide us with clues about the increasing incidence of PCa in younger individuals and the importance of early screening. Data from the European Randomized Study of Screening for Prostate Cancer (ERSPC) revealed that PSA screening resulted in a significant 20% reduction in mortality from PCa (Schröder et al., 2014). However, the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening trial in the United States revealed an increased incidence of cancer in the screening group, but no cancer-specific mortality benefit from PSA screening after 13 years of follow-up (Andriole et al., 2012). However, it is important to consider differences in economy, culture, and medical health care level across different regions. Presently, China’s medical health care level remains lagging behind that of Europe and the United States. Only three cases of early localized PCa were detected in our study, and the proportion of early localized PCa still needs to be improved.

For surgical treatment, Bill-Axelson et al. (2018) reported that the tumor-specific survival rate of limited, medium-low risk patients after radical prostatectomy reached 80.4% at 23 years. Radical prostatectomy may be the first choice of treatment for these patients. Wallis et al. (2016) reported that among patients with localized PCa, there was no significant difference in 10-year overall survival rate between radical prostatectomy and radical radiotherapy. However, we found four patients with localized PCa, who received internal radiotherapy and endocrine therapy for fear of urinary incontinence and other complications after radical prostatectomy. Many studies have reported that comprehensive treatment with radical prostatectomy as the main treatment for locally advanced PCa could yield good survival benefits to patients (Costello, 2020; Marra et al., 2020; Pansadoro & Brassetti, 2019). In our study, four patients with locally advanced PCa, who underwent radical prostatectomy and lymphadenectomy, were currently undergoing outpatient follow-up for PSA. Adjuvant therapy is recommended if the indicator of PSA rebounds or metastases occurs.

Clinical Practice

We found that 3,477 (48.5%) age-eligible residents in the Luqiao district of Taizhou, China, did not participate in this PCa screening study. This means that there remains a large number of residents with PCa who were not diagnosed in this study. We received some feedback from the local health center directors and found that more than one half of the residents did not participate in screening because they were not aware of PCa. Mobilizing the local population to actively participate in PCa screening was an issue in this study that warranted attention. Durkin et al. (2020) reported that mass media campaigns increased participation in bowel cancer screening. Hoffmeister et al. (2017) reported that targeted invitations significantly increased participation in cancer screening. A systematic review and meta-analysis of rectal cancer screening suggested that the decision to participate in colorectal cancer screening depends on individual perceptions of colorectal cancer screening (Honein-AbouHaidar et al., 2016). Factors mediating awareness included public education to address misconceptions, primary care physician efforts to recommend screening, and the influence of friends and family (Honein-AbouHaidar et al., 2016; Wilkes et al., 2013). Perhaps compliance and actual participation in PCa screening can be improved when residents’ awareness shifts from passive to active screening.

Clinical Suggestions

Establishment of a Professional Team

There were 356 (10%) male residents who did not participate in the screening and reported that they did not receive easy-to-understand answers to their questions on site. This may be because primary care physicians do not have specialized knowledge of PCa and lack awareness of early screening. A randomized controlled study reported that primary care physicians have the ability to screen for PCa. A randomized controlled study reported that primary care physicians’ education and patient activation had a significant impact on their attitude toward screening (Wilkes et al., 2013). We need to make some changes to this current screening model, such as establishing a professional team to regularly train primary care physicians to improve their knowledge and sending urologists to conduct on-site consultations.

Painless Transperineal Prostate Biopsy

Regardless of the type of local prostate anesthesia used, it would—more or less—result in discomfort, including pain and anxiety, among patients (Hizli et al., 2015; Packiam et al., 2018). Five patients in our study declined the invasive procedure due to fear of complications associated with prostate biopsy. Therefore, it was important to provide effective and even painless control for prostate biopsy. For patients who did not want to undergo prostate biopsy with local anesthesia, transperineal prostate biopsy combined with general anesthesia may be a good option to reduce their concerns. Although TRUS prostate biopsy is a standard procedure for the diagnosis of PCa (Fabiani et al., 2016). In terms of complications, transperineal prostate biopsy—compared with transrectal prostate biopsy—had obvious advantages in reducing the incidence of infection and patients did not need to worry about intestinal bleeding (Borkowetz et al., 2018; Saito et al., 2017). In addition, Borkowetz et al. (2018) reported that the targeted puncture of MRI/ultrasonography fusion could significantly improve the detection rate of PCa and reduce the number of unnecessary needle punctures. In this study, our hospital did not have such dedicated equipment; as such, the 26 patients with abnormal PSA levels but negative biopsy results might have PCa.

Combination of Artificial Intelligence

Applying PSA or combining it with an advanced technology in PCa screening warrants serious consideration. Follow-up and observation are needed to determine whether screening models that include advanced technology and equipment, combined with new drugs or combination therapies, can reduce PCa-related mortality. Distler et al. (2017) reported that using PSA density combined with mpMRI improved the negative predictive value of PI-RADS scoring. In this study, a total of 82 residents did not undergo prostate biopsy but were recommended for follow-up with t-PSA and PI-RADS. Artificial intelligence is gradually changing the traditional medical model, which is the direction and trend of human medical development in the future. Reda et al. (2018) developed an artificial intelligence system based on MRI and PSA test results, which could avoid unnecessary prostate biopsies, reduce diagnostic costs, and avoid complications of diagnostic methods.

Limitations

A previous study reported that biopsy-detected PCa, including high-grade cancers, was not rare among men with PSA levels ≤4.0 ng/mL—levels generally believed to be in the normal range (Thompson et al., 2004). Therefore, there were some residents in whom PCa was undoubtedly missed in our screening model. Consensus among Chinese PCa experts suggested that serum PSA testing should be performed as early as possible for groups at high risk of PCa, including males >50 years of age, males >45 years of age with a family history of PCa, males >40 years of age with PSA levels > 1 μg/L, and males >40 years of age with BRCA2 (breast cancer 2) gene mutation (Prostate Cancer Group, Urogenital Tumor Professional Committee, Chinese Anti-cancer Association, 2017). However, a previous study (Fu et al., 2020) showed that the incidence of prostate cancer was not high in Chinese male residents below the age of 50, and the financial resources of this study were limited. The baseline (i.e., minimum) age of the subjects in this study was 50 years; as such, high-risk men <50 years of age were not screened for PCa. Finally, in this study, prostate biopsy was not recommended for subjects with t-PSA levels between 4 and 10 μg/L and PI-RADS < 3, in whom a diagnosis of PCa may have been missed. This study took place between October 2020 and December 2020. In analyzing why residents were not screened, we did not take into account that residents were unable or unwilling to be screened due to fear of Corona Virus Disease 2019 (COVID-19), lockdowns, social distancing, and other reasons. In addition, this study has limited generalizability outside of similar districts in China. In particular, it will have very little generalizability to countries with established screening guidelines and programs.

Conclusion

In this study, age and t-PSA were used as primary screening indicators, which were further combined with mpMRI and prostate biopsy to diagnose PCa. The detection rate of PCa in this study was 0.45% (16/3524); however, the actual incidence may be higher. Although this was a relatively effective and convenient screening mode, 3,477 (48.5%) age-eligible residents did not participate in this PCa screening study; as such, further enhancing public education and knowledge to increase resident awareness and participation in PCa screening programs should be promoted.

Footnotes

Acknowledgements

We thank the government and the hospital team for their support of this study.

Ethics Approval and Consent to Participate

Our hospital ethics committees (Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, China) reviewed and approved this study (NO. K20210402). The principles of the Helsinki Declaration were followed in this study.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported in the scientific research fund of the Taizhou Enze Medical Center Group (No. 2021EZZDC04)

ORCID iD

Tao-Hsin Tung

References

Ahmed

H. U.

El-Shater Bosaily

Brown

L. C.

Gabe

Kaplan

Parmar

M. K.

Collaco-Moraes

Ward

Hindley

R. G.

Freeman

Kirkham

A. P.

Oldroyd

Parker

Emberton

& PROMIS Study Group. (2017). Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): A paired validating confirmatory study. The Lancet, 389(10071), 815–822. https://doi.org/10.1016/s0140-6736(16)32401-1

Andriole

G. L.

Crawford

E. D.

Grubb

R. L.

3rd Buys

S. S.

Chia

Church

T. R.

Fouad

M. N.

Isaacs

Kvale

P. A.

Reding

D. J.

Weissfeld

J. L.

Yokochi

L. A.

Brien

Ragard

L. R.

Clapp

J. D.

Rathmell

J. M.

Riley

T. L.

Hsing

A. W.

. . .Prorok

P. C.

(2012). Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: Mortality results after 13 years of follow-up. Journal of the National Cancer Institute, 104(2), 125–132. https://doi.org/10.1093/jnci/djr500

Bernal-Soriano

M. C.

Parker

L. A.

López-Garrigos

Hernández-Aguado

Caballero-Romeu

J. P.

Gómez-Pérez

Alfayate-Guerra

Pastor-Valero

García

Lumbreras

(2019). Factors associated with false negative and false positive results of prostate-specific antigen (PSA) and the impact on patient health: Cohort study protocol. Medicine (Baltimore), 98(40), e17451. https://doi.org/10.1097/md.0000000000017451

Bill-Axelson

Holmberg

Garmo

Taari

Busch

Nordling

Häggman

Andersson

S. O.

Andrén

Steineck

Adami

H. O.

Johansson

J. E.

(2018). Radical prostatectomy or watchful waiting in prostate cancer—29-year follow-up. The New England Journal of Medicine, 379(24), 2319–2329. https://doi.org/10.1056/NEJMoa1807801

Borkowetz

Hadaschik

Platzek

Toma

Torsev

Renner

Herout

Baunacke

Laniado

Baretton

Radtke

J. P.

Kesch

Hohenfellner

Froehner

Schlemmer

H. P.

Wirth

Zastrow

(2018). Prospective comparison of transperineal magnetic resonance imaging/ultrasonography fusion biopsy and transrectal systematic biopsy in biopsy-naïve patients. BJU International, 121(1), 53–60. https://doi.org/10.1111/bju.14017

Costello

A. J.

(2020). Considering the role of radical prostatectomy in 21st century prostate cancer care. Nature Reviews Urology, 17(3), 177–188. https://doi.org/10.1038/s41585-020-0287-y

de Oliveira

Guimarães

G. C.

Mourão

T. C.

Favaretto

R. L.

Santana

Lopes

Zequi

S. C

. (2021). Prostate cancer screening in Brazil: A single center experience in the public health system. International Brazilian Journal of Urology, 47(3), 558–565. https://doi.org/10.1590/s1677-5538.Ibju.2020.0392

De Visschere

Oosterlinck

De Meerleer

Villeirs

. (2010). Clinical and imaging tools in the early diagnosis of prostate cancer, a review. Journal of the Belgian Society of Radiology, 93(2), 62–70. https://doi.org/10.5334/jbr-btr.121

Distler

F. A.

Radtke

J. P.

Bonekamp

Kesch

Schlemmer

H. P.

Wieczorek

Kirchner

Pahernik

Hohenfellner

Hadaschik

B. A.

(2017). The value of PSA density in combination with PI-RADS™ for the accuracy of prostate cancer prediction. The Journal of Urology, 198(3), 575–582. https://doi.org/10.1016/j.juro.2017.03.130

10.

Durkin

Broun

Guerin

Morley

Wakefield

(2020). Impact of a mass media campaign on participation in the Australian bowel cancer screening program. Journal of Medical Screening, 27(1), 18–24. https://doi.org/10.1177/0969141319874372

11.

Fabiani

Servi

Filosa

Fioretti

Maurelli

Tombolini

Tallè

Mammana

(2016). May ultrasound probe size influence pain perception of needle piercing during transrectal prostate biopsy? A prospective evaluation. Archivio Italiano di Urologia Andrologia, 88(3), 223–227. https://doi.org/10.4081/aiua.2016.3.223

12.

Faria

E. F.

Carvalhal

G. F.

Vieira

R. A.

Silva

T. B.

Mauad

E. C.

Carvalho

A. L.

(2010). Program for prostate cancer screening using a mobile unit: Results from Brazil. Urology, 76(5), 1052–1057. https://doi.org/10.1016/j.urology.2010.02.044

13.

Z. T.

Guo

X. L.

Zhang

S. W.

Zheng

R. S.

Zeng

H. M.

Chen

Wang

S. M.

Sun

K. X.

Wei

W. W.

(2020). Statistical analysis of incidence and mortality of prostate cancer in China, 2015. Zhonghua zhong liu za zhi [Chinese Journal of Oncology], 42(9), 718–722. https://doi.org/10.3760/cma.j.cn112152-20200313-00200

14.

Hizli

Argun

Özkul

Güven

Arik

A. I.

Başay

Köşüş

Günaydin

Başar

(2015). Novel approach for pain control in patients undergoing prostate biopsy: Iliohypogastric nerve block with or without topical application of prilocaine-lidocaine: A randomized controlled trial. Urology Journal, 12(1), 2014–2019. https://doi.org/10.22037/uj.v12i1.2689

15.

Hoffmeister

Holleczek

Zwink

Stock

Stegmaier

Brenner

(2017). Screening for bowel cancer: Increasing participation via personal invitation. Deutsches Aärzteblatt International, 114(6), 87–93. https://doi.org/10.3238/arztebl.2017.0087

16.

Honein-AbouHaidar

G. N.

Kastner

Vuong

Perrier

Daly

Rabeneck

Straus

Baxter

N. N.

(2016). Systematic review and meta-study synthesis of qualitative studies evaluating facilitators and barriers to participation in colorectal cancer screening. Cancer Epidemiology Biomarkers and Prevention, 25(6), 907–917. https://doi.org/10.1158/1055-9965.Epi-15-0990

17.

Hötker

Donati

O. F.

(2021). PI-RADS 2.1 and structured reporting of magnetic resonance imaging of the prostate. Radiologe, 61(9), 802–809. https://doi.org/10.1007/s00117-021-00868-6

18.

Ilic

Neuberger

M. M.

Djulbegovic

Dahm

(2013). Screening for prostate cancer. Cochrane Database of Systematic Reviews, 2013(1), CD004720. https://doi.org/10.1002/14651858.CD004720.pub3

19.

Kitagawa

Mizokami

Nakashima

Koshida

Shimamura

Miyazaki

Koyama

Namiki

(2011). Clinical outcomes of prostate cancer patients detected by prostate-specific antigen-based population screening in Kanazawa City, Japan. International Journal of Urology, 18(8), 592–596. https://doi.org/10.1111/j.1442-2042.2011.02796.x

20.

Klotz

Lughezzani

Maffei

Sánchez

Pereira

J. G.

Staerman

Cash

Luger

Lopez

Sanchez-Salas

Abouassaly

Shore

N. D.

Eure

Paciotti

Astobieta

Wiemer

Hofbauer

Heckmann

Gusenleitner

. . .Klein

(2021). Comparison of micro-ultrasound and multiparametric magnetic resonance imaging for prostate cancer: A multicenter, prospective analysis. Canadian Urological Association Journal, 15(1), E11–E16. https://doi.org/10.5489/cuaj.6712

21.

Liang

Zhao

X. Z.

Shi

J. Y.

Qiu

X. F.

Zhang

Zhuang

J. L.

Wang

Deng

Y. M.

Huang

H. F.

Zhang

C. W.

Guo

H. Q.

(2019). Combination of serum PSA assay, multi-parametric MRI and targeted prostate biopsy for prostate cancer screening in Nanjing. Zhonghua nan ke xue = National Journal of Andrology, 25(9), 815–822. https://doi.org/10.13263/j.cnki.nja.2019.09.008

22.

Liu

Zhang

Z. J.

(2019). Trends and age-period-cohort effect on incidence and mortality of prostate cancer from 1990 to 2017 in China. Public Health, 172, 70–80. https://doi.org/10.1016/j.puhe.2019.04.016

23.

C. G.

D. W.

C. L.

Zhou

F. J.

Yao

X. D.

Zhang

S. L.

Dai

Zhang

H. L.

Zhu

Shen

Y. J.

(2008). Epidemiology of prostate cancer from three centers and analysis of the first-line hormonal therapy for the advanced disease. Zhonghua wai ke za zhi [Chinese Journal of Surgery], 46(12), 921–925. https://doi.org/10.3321/j.issn:0529-5815.2008.12.012

24.

Marra

Valerio

Heidegger

Tsaur

Mathieu

Ceci

Ploussard

van den Bergh

Kretschmer

Thibault

Ost

Tilki

Kasivisvanathan

Moschini

Sanchez-Salas

Gontero

Karnes

R. J.

Montorsi

Gandaglia

(2020). Management of patients with node-positive prostate cancer at radical prostatectomy and pelvic lymph node dissection: A systematic review. European Urology Oncology, 3(5), 565–581. https://doi.org/10.1016/j.euo.2020.08.005

25.

Martin

R. M.

Donovan

J. L.

Turner

E. L.

Metcalfe

Young

G. J.

Walsh

E. I.

Lane

J. A.

Noble

Oliver

S. E.

Evans

Sterne

Holding

Ben-Shlomo

Brindle

Williams

N. J.

Hill

E. M.

S. Y.

Toole

Tazewell

M. K.

Hamdy

F. C.

(2018). Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: The CAP randomized clinical trial. The Journal of the American Medical Association, 319(9), 883–895. https://doi.org/10.1001/jama.2018.0154

26.

Merriel

Funston

Hamilton

(2018). Prostate cancer in primary care. Advances in Therapy, 35(9), 1285–1294. https://doi.org/10.1007/s12325-018-0766-1

27.

Packiam

V. T.

Nottingham

C. U.

Cohen

A. J.

Eggener

S. E.

Gerber

G. S.

(2018). No effect of music on anxiety and pain during transrectal prostate biopsies: A randomized trial. Urology, 117, 31–35. https://doi.org/10.1016/j.urology.2018.04.014

28.

Palsdottir

Nordstrom

Karlsson

Grönberg

Clements

Eklund

(2019). The impact of different prostate-specific antigen (PSA) testing intervals on Gleason score at diagnosis and the risk of experiencing false-positive biopsy recommendations: A population-based cohort study. BMJ Open, 9(3), Article e027958. https://doi.org/10.1136/bmjopen-2018-027958

29.

Pansadoro

Brassetti

(2019). Extrafascial robot-assisted laparoscopic radical prostatectomy in locally advanced prostate cancer. Minerva Chirurgica, 74(1), 78–87. https://doi.org/10.23736/s0026-4733.18.07759-3

30.

Patasius

Krilaviciute

Smailyte

(2020). Prostate cancer screening with PSA: Ten years’ experience of population based early prostate cancer detection programme in Lithuania. Journal of Clinical Medicine, 9(12), 3826. https://doi.org/10.3390/jcm9123826

31.

Prostate Cancer Working Group of Genitourinary Cancer Committee in Chinese Anti-Cancer Association. (2017). Consensus of prostate cancer screening. Zhonghua Wai Ke Za Zhi, 55(5), 340-342 (in Chinese). https://doi.org/10.3760/cma.j.issn.0529-5815.2017.05.005

32.

Rao

A. R.

Motiwala

H. G.

Karim

O. M.

(2008). The discovery of prostate-specific antigen. BJU International, 101(1), 5–10. https://doi.org/10.1111/j.1464-410X.2007.07138.x

33.

Reda

Khalil

Elmogy

Abou El-Fetouh

Shalaby

Abou El-Ghar

Elmaghraby

Ghazal

El-Baz

(2018). Deep learning role in early diagnosis of prostate cancer. Technology in Cancer Research & Treatment, 17, 1533034618775530. https://doi.org/10.1177/1533034618775530

34.

Saito

Washino

Nakamura

Konishi

Ohshima

Arai

Miyagawa

(2017). Transperineal ultrasound-guided prostate biopsy is safe even when patients are on combination antiplatelet and/or anticoagulation therapy. BMC Urology, 17(1), Article 53. https://doi.org/10.1186/s12894-017-0245-z

35.

Schröder

F. H.

Hugosson

Roobol

M. J.

Tammela

T. L.

Ciatto

Nelen

Kwiatkowski

Lujan

Lilja

Zappa

Denis

L. J.

Recker

Berenguer

Määttänen

Bangma

C. H.

Aus

Villers

Rebillard

van der Kwast

. . .Auvinen

(2009). Screening and prostate-cancer mortality in a randomized European study. The New England Journal of Medicine, 360(13), 1320–1328. https://doi.org/10.1056/NEJMoa0810084

36.

Schröder

F. H.

Hugosson

Roobol

M. J.

Tammela

T. L.

Zappa

Nelen

Kwiatkowski

Lujan

Määttänen

Lilja

Denis

L. J.

Recker

Paez

Bangma

C. H.

Carlsson

Puliti

Villers

Rebillard

Hakama

. . .Auvinen

(2014). Screening and prostate cancer mortality: Results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. The Lancet, 384(9959), 2027–2035. https://doi.org/10.1016/s0140-6736(14)60525-0

37.

Thompson

I. M.

Pauler

D. K.

Goodman

P. J.

Tangen

C. M.

Lucia

M. S.

Parnes

H. L.

Minasian

L. M.

Ford

L. G.

Lippman

S. M.

Crawford

E. D.

Crowley

J. J.

Coltman

C. A.

Jr. (2004). Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. The New England Journal of Medicine, 350(22), 2239–2246. https://doi.org/10.1056/NEJMoa031918

38.

Wallis

Saskin

Choo

Herschorn

Kodama

R. T.

Satkunasivam

Shah

P. S.

Danjoux

Nam

R. K.

(2016). Surgery versus radiotherapy for clinically-localized prostate cancer: A systematic review and meta-analysis. European Urology, 70(1), 21–30. https://doi.org/10.1016/j.eururo.2015.11.010

39.

Wang

B. H.

Sha

Y. T.

F. D.

(2020). The value of prostate-specific antigen in the early detection of prostate cancer in Chinese population: A meta-analysis. Chinese Journal of Cancer, 30(11), Article 8. https://doi.org/10.19401/j.cnki.1007-3639.2020.11.005 (in Chinese)

40.

Wang

Liu

Zhu

Chen

Wan

Wang

J. Y.

(2013). Analysis of prostate specific antigen screening results in people over 50 years old in Beijing area. Chinese Journal of Urology, 34(06), 462–465. https://doi.org/10.3760/cma.j.issn.1000-6702.2013.06.017 (in Chinese)

41.

Weinreb

J. C.

Barentsz

J. O.

Choyke

P. L.

Cornud

Haider

M. A.

Macura

K. J.

Margolis

Schnall

M. D.

Shtern

Tempany

C. M.

Thoeny

H. C.

Verma

(2016). PI-RADS prostate imaging—Reporting and data system: 2015, version 2. European Urology, 69(1), 16–40. https://doi.org/10.1016/j.eururo.2015.08.052

42.

Wilkes

M. S.

Day

F. C.

Srinivasan

Griffin

Tancredi

D. J.

Rainwater

J. A.

Kravitz

R. L.

Bell

D. S.

Hoffman

J. R.

(2013). Pairing physician education with patient activation to improve shared decisions in prostate cancer screening: A cluster randomized controlled trial. Annals of Family Medicine, 11(4), 324–334. https://doi.org/10.1370/afm.1550

43.

Zhen

Liu

Yegang

Yongjiao

Yawei

Jiaqi

Xianhao

Yuxuan

Rui

Wei

Ningjing

(2019). Accuracy of multiparametric magnetic resonance imaging for diagnosing prostate Cancer: A systematic review and meta-analysis. BMC Cancer, 19(1), Article 1244. https://doi.org/10.1186/s12885-019-6434-2

Using “Age and Total-PSA” as the Main Indicators: The Results of Taizhou Integrated Prostate Screening (No 2)

Abstract

Keywords

Introduction

Method

Study Population

Study Protocol

Exclusion Criteria

Screening Process for PCa

Serum t-PSA Protocol

Noninvasive Examination

Transperineal Biopsy of the Prostate

TNM Staging and Pathological Grading

Treatment and Follow-Up

Statistical Analysis

Results

Subject Characteristics

PCa Screening Results

Characteristics of Subjects With Confirmed PCa

Outpatient Follow-Up in Patients Diagnosed With PCa

Discussion

Clinical Implications

Clinical Practice

Clinical Suggestions

Establishment of a Professional Team

Painless Transperineal Prostate Biopsy

Combination of Artificial Intelligence

Limitations

Conclusion

Footnotes

Acknowledgements

Ethics Approval and Consent to Participate

Declaration of Conflicting Interests

Funding

ORCID iD

References