Xiaohao Ruan’s research while affiliated with Shanghai Jiao Tong University and other places

Background Anticipating the postoperative pathological stage and potential for adverse features of prostate cancer (PCa) patients before radical prostatectomy (RP) is crucial for guiding perioperative treatment. Methods A cohort consisting of three sub‐cohorts with a total of 709 patients has been enlisted from two major tertiary medical centres in China. The primary assessment parameters for adverse pathological features in this study are the pathological T stage, the AJCC prognostic stage groups and perineural invasion (PNI). Logistic regression analyses were performed to investigate the relationship between prostate specific antigen (PSA), its derivatives (incluing Prostate Health Index, phi and phi density, phiD), and the pathological outcomes after RP. Results Both phi and phiD showed a significant association with pathologic T stage of pT3 or above (phi, adjusted OR, AOR = 2.82, 95% confidence interval, 95% CI: 1.88–4.23, p < 0.001; phiD, AOR = 2.47, 95% CI: 1.76–3.48, p < 0.001) and PNI (phi, AOR = 2.15, 95% CI: 1.39–3.32, p < 0.001; phiD, AOR = 1.94, 95% CI: 1.38–2.73, p < 0.001). In a subgroup analysis with a total PSA value <10 ng/mL, phi and phiD continued to show a significant correlation with pT3 or above (phi, AOR = 4.70, 95% CI: 1.29–17.12, p = 0.019; phiD, AOR = 3.44, 95% CI: 1.51–7.85, p = 0.003), and phiD also maintained its predictive capability for PNI in this subgroup (AOR = 2.10, 95% CI: 1.17–3.80, p = 0.014). Sensitivity analysis indicated that the findings in the combined cohort are mainly influenced by one of the sub‐cohorts, partially attributable to disparities in sample sizes between sub‐cohorts. Combined analysis of phi(D) and multiparametric MRI (mpMRI) data yielded similar results. Conclusions Preoperative measurement of serum phi and phiD is valuable for predicting the occurrence of adverse pathological features in Chinese PCa patients after RP.

Backgrounds: Urinary stone disease (USD, or urolithiasis) is common and poses a significant healthcare burden and health economic burden in a working-age population. We aim to provide epidemiological insights into the prevalence, incidence, trends, and risk factors of USD among the Chinese population. Methods: A prospective cohort study of 966,481 participants from the CHinese Electronic health Records Research during 2009-2022 in Yinzhou, China (CHERRY). Temporal trends were estimated by annual percentage changes (APC) using Joinpoint regression analyses. A stratified Cox proportional hazards regression and propensity score analyses were used to assess the effect of potential risk factors, population attribution factor (PAF) and number needed to prevent (NNTP). Results: Between 2014/2015 and 2021, there was an annualized increase in USD incidence by 5.3-6.8% (P<0.05). Tobacco smoking, alcohol drinking, high body mass index, diabetes, hyperlipidemia, hypertension, and heart disease were identified as risk factors while regular exercising was a protective factor of USD. PAF ranged from 22.5% in regular exercising (weekly) to 1.3% in non-drinking behavior. NNTP ranged from 21 in weekly exercising to 182 in non-smoking behavior. Conclusions: USD is a common disease affecting about 1 in 10 Chinese, and the incidence increased by 5-6% annually over the past 6-7 years. Lifestyle factors and metabolic symptoms are potential risk factors for USD.

Objective This study aimed to figure out whether the combination of the prostate health index (PHI) and prostate-specific membrane antigen (PSMA)-PET/MR could improve the diagnostic accuracy for prostate cancer (PCa) than that of each individual method used alone. Methods In this prospective, observational study, 41 patients who underwent the systematic prostate biopsy between June 2019 and September 2022 were enrolled. Both the PHI test and ¹⁸F-PSMA-1007-PET/MR were performed prior to biopsies. The diagnostic accuracy of different models was compared by logistic regression, areas under the curve (AUCs) of the receiver operating characteristic, and net reclassification index (NRI). Results Among the 41 patients, 14 (34.1%) were pathologically diagnosed with PCa. The PHI in the PCa group was significantly higher than that in the benign group (44.4 vs. 35.0, p=0.048). Similarly, all the patients in the PCa group received positive results of ¹⁸F-PSMA-1007-PET/MR, of which the positive rate was significantly higher than that in benign group (100% vs. 62.96%, p=0.025). The ¹⁸F-PSMA-1007-PET/MR provided additional diagnostic values to the PHI (AUC: 0.802 vs. 0.692, p=0.025). However, there was no significant difference between the combination model and the ¹⁸F-PSMA-1007-PET/MR alone (AUC 0.802 vs. 0.685, p=0.071). The optimal PHI cutoff of the combination model is 32, with which the model could significantly reduce unnecessary biopsies (NRI: 22.22%, 95% confidence interval: 6.54%–37.90%, p=0.005). However, among patients with the PHI of ≥43.5, there was no significant difference between the combination model and the PHI alone (NRI: 11.11%, 95% confidence interval: −0.74%–22.97%, p=0.066). Conclusion The combination of the PHI and ¹⁸F-PSMA-1007-PET/MR outperforms the PHI alone for predicting PCa, especially in avoiding unnecessary biopsies. However, for patients with the PHI of ≥43.5, the addition of ¹⁸F-PSMA-1007-PET/MR to the PHI does not yield additional benefits.

Background The status of prostate-specific antigen (PSA) screening is unclear in China. Evidence regarding the optimal frequency and interval of serial screening for prostate cancer (PCa) is disputable. Objective This study aimed to depict the status of PSA screening and to explore the optimal screening frequency for PCa in China. Methods A 13-year prospective cohort study was conducted using the Chinese Electronic Health Records Research in Yinzhou study’s data set. A total of 420,941 male participants aged ≥45 years were included between January 2009 and June 2022. Diagnosis of PCa, cancer-specific death, and all-cause death were obtained from the electronic health records and vital statistic system. Hazard ratios (HRs) with 95% CIs were estimated using Cox regression analysis. Results The cumulative rate of ever PSA testing was 17.9% with an average annual percent change (AAPC) of 8.7% (95% CI 3.6%-14.0%) in the past decade in China. People with an older age, a higher BMI, higher waist circumference, tobacco smoking and alcohol drinking behaviors, higher level of physical activity, medication use, and comorbidities were more likely to receive PSA screening, whereas those with a lower education level and a widowed status were less likely to receive the test. People receiving serial screening ≥3 times were at a 67% higher risk of PCa detection (HR 1.67; 95% CI 1.48-1.88) but a 64% lower risk of PCa-specific mortality (HR 0.36; 95% CI 0.18-0.70) and a 28% lower risk of overall mortality (HR 0.72; 95% CI 0.67-0.77). People following a serial screening strategy at least once every 4 years were at a 25% higher risk of PCa detection (HR 1.25; 95% CI 1.13-1.36) but 70% (HR 0.30; 95% CI 0.16-0.57) and 23% (HR 0.77; 95% CI 0.73-0.82) lower risks of PCa-specific and all-cause mortality, respectively. Conclusions This study reveals a low coverage of PSA screening in China and provides the first evidence of its benefits in the general Chinese population. The findings of this study indicate that receiving serial screening at least once every 4 years is beneficial for overall and PCa-specific survival. Further studies based on a nationwide population and with long-term follow-up are warranted to identify the optimal screening interval in China.

Background The risk of second primary cancers (SPC) is increasing after the first primary cancers (FPC) are diagnosed and treated. The underlying causal relationship remains unclear. Methods We conducted a pan-cancer association (26 cancers) study in the Surveillance, Epidemiology, and End Results (SEER) database (non-Hispanic whites). The standardized incidence ratio (SIR) was estimated as the risk of SPCs in cancer survivors based on the incidence in the general population. Furthermore, the causal effect was evaluated by two-sample Mendelian Randomization (MR, 13 FPCs) in the UK Biobank (UKB, n=459,136,, European whites) and robust analysis (radial MR and Causal Analysis Using Summary Effect estimates, CAUSE). Results We found 11 significant cross-correlations among different cancers after harmonizing SIR and MR results. Whereas only 4 of them were confirmed by MR to have a robust causal relationship. In particular, patients initially diagnosed with oral pharyngeal cancer would have an increased risk of non-Hodgkin lymphoma (SIR SEER = 1.18, 95%Confidence Interval [CI]:1.05–1.31, OR radial-MR =1.21, 95% CI:1.13–1.30, p=6.00 × 10 ⁻³ ; OR cause = 1.17, 95% CI:1.05–1.31, p=8.90 × 10 ⁻³ ). Meanwhile, ovary cancer was identified to be a risk factor for soft tissue cancer (SIR SEER = 1.72, 95%Confidence Interval [CI]:1.08–2.60, OR radial-MR =1.39, 95% CI:1.22–1.58, p=1.07 × 10 ⁻³ ; OR cause = 1.36, 95% CI:1.16–1.58, p=0.01). And kidney cancer was likely to cause the development of lung cancer (SIR SEER = 1.28, 95%Confidence Interval [CI]:1.22–1.35, OR radial-MR =1.17, 95% CI:1.08–1.27, p=6.60 × 10 ⁻³ ; OR cause = 1.16, 95% CI:1.02–1.31, p=0.05) and myeloma (SIR SEER = 1.54, 95%Confidence Interval [CI]:1.33–1.78, OR radial-MR =1.72, 95% CI:1.21–2.45, p=0.02; OR cause = 1.49, 95% CI:1.04–2.34, p=0.02). Conclusions A certain type of primary cancer may cause another second primary cancer, and the profound mechanisms need to be studied in the future. Funding This work was in supported by grants from National Natural Science Foundation of China (Grant No. 81972645), Innovative research team of high-level local universities in Shanghai, Shanghai Youth Talent Support Program, intramural grant of The University of Hong Kong to Dr. Rong Na, and Shanghai Sailing Program (22YF1440500) to Dr. Da Huang.

The aim of liquid biopsies is to obtain tumor information via the molecular interrogation of liquid samples, including blood and urine. As a minimally invasive procedure, liquid biopsies have attracted attention. A series of studies have reported associations of biomarkers such as circulating tumor DNA, cell-free DNA and extracellular vesicles with urological cancers, especially prostate cancer (PCa), and demonstrated the promising potential of liquid biopsies. In this review, we summarize recent clinical translational studies of liquid biopsies in PCa and other urological cancers, including bladder cancer and renal cell carcinoma. The number of translational studies was limited, and most of the studies focused on PCa. Biomarkers isolated from blood by different detection methods could be applied in clinical practice to predict prognosis and treatment response in advanced PCa. The other applications in urological cancers identified in previous studies remain to be explored further. Current studies are limited due to the lack of ideal standard detection methods for biomarkers. In the future, with advances in methodology, more translational studies will be conducted to identify potential applications of liquid biopsies in urological cancers.

Background The genetic risk of aggressive prostate cancer (PCa) is hard to be assessed due to the lack of aggressiveness-related single-nucleotide polymorphisms (SNPs). Prostate volume (PV) is a potential well-established risk factor for aggressive PCa, we hypothesize that polygenic risk score (PRS) based on benign prostate hyperplasia (BPH) or PV-related SNPs may also predict the risk of aggressive PCa or PCa death. Methods We evaluated a PRS using 21 BPH/PV-associated SNPs, two established PCa risk-related PRS and 10 guideline-recommended hereditary cancer risk genes in the population-based UK Biobank cohort (N = 209,502). Results The BPH/PV PRS was significantly inversely associated with the incidence of lethal PCa as well as the natural progress in PCa patients (hazard ratio, HR = 0.92, 95% confidence interval [CI]: 0.87–0.98, P = 0.02; HR = 0.92, 95% CI 0.86–0.98, P = 0.01). Compared with men at the top 25th PRS, PCa patients with bottom 25th PRS would have a 1.41-fold (HR, 95% CI 1.16–1.69, P = 0.001) increased PCa fatal risk and shorter survival time at 0.37 yr (95% CI 0.14–0.61, P = 0.002). In addition, patients with BRCA2 or PALB2 pathogenic mutations would also have a high risk of PCa death (HR = 3.90, 95% CI 2.34–6.51, P = 1.79 × 10–7; HR = 4.29, 95% CI 1.36–13.50, P = 0.01, respectively). However, no interactive but independent effects were detected between this PRS and pathogenic mutations. Conclusions Our findings provide a new measurement of PCa patients’ natural disease outcomes via genetic risk ways.

Background: Telomerase reverse transcriptase (TERT) has been consistently associated with prostate cancer (PCa) risk. However, few studies have explored the association between TERT variants and PCa aggressiveness. Methods: Individual and genetic data were obtained from UK Biobank and a Chinese PCa cohort (Chinese Consortium for Prostate Cancer Genetics). Results: A total of 209,694 Europeans (14,550 PCa cases/195,144 controls) and 8873 Chinese (4438 cases/4435 controls) were involved. Nineteen susceptibility loci with five novel ones (rs144704378, rs35311994, rs34194491, rs144020096, and rs7710703) were detected in Europeans, whereas seven loci with two novel ones (rs7710703 and rs11291391) were discovered in the Chinese cohort. The index SNP for the two ancestries was rs2242652 (odds ratio [OR] = 1.16, 95% confidence interval [CI]:1.12-1.20, p = 4.12 × 10-16) and rs11291391 (OR = 1.73, 95%CI:1.34-2.25, p = 3.04 × 10-5), respectively. SNPs rs2736100 (OR = 1.49, 95%CI:1.31-1.71, p = 2.91 × 10-9) and rs2853677 (OR = 1.74, 95%CI:1.52-1.98, p = 3.52 × 10-16) were found significantly associated with aggressive PCa, while rs35812074 was marginally related to PCa death (hazard ratio [HR] = 1.61, 95%CI:1.04-2.49, p = 0.034). Gene-based analysis showed a significant association of TERT with PCa (European: p = 3.66 × 10-15, Chinese: p = 0.043) and PCa severity (p = 0.006) but not with PCa death (p = 0.171). Conclusion: TERT polymorphisms were associated with prostate tumorigenesis and severity, and the genetic architectures of PCa susceptibility loci were heterogeneous among distinct ancestries.

Simple Summary As lifestyle intervention has come to the fore for cancer prevention, the causal effect of lifestyle behaviors on prostate cancer remains to be elucidated. No comparison across different ethnicities has been conducted previously. In this study, we used a novel instrumental variable methodology, namely, Mendelian randomization analysis, to explore the associations between a wide range of behavioral factors and prostate cancer in both Europeans and East Asians. The results of this study showed that lifetime tobacco smoking was positively related to an increased prostate cancer risk in Europeans. In East Asians, alcohol consumption and delayed sexual initiation were risk factors, while vegetable intake was a protective factor for prostate cancer. These findings largely broaden the evidence base for the spectrum of risk factors for prostate cancer, and provide insights into the priority of behavioral interventions for high-risk groups in different population settings. Abstract Objective: Early evidence is disputable for the effects of modifiable lifestyle behaviors on prostate cancer (PCa) risk. No research has yet appraised such causality in different ancestries using a Mendelian randomization (MR) approach. Methods: A two-sample univariable and multivariable MR analysis was performed. Genetic instruments associated with lifestyle behaviors were selected based on genome-wide association studies. Summary-level data for PCa were obtained from PRACTICAL and GAME-ON/ELLIPSE consortia for Europeans (79,148 PCa cases and 61,106 controls), and ChinaPCa consortium for East Asians (3343 cases and 3315 controls). Replication was performed using FinnGen (6311 cases and 88,902 controls) and BioBank Japan data (5408 cases and 103,939 controls). Results: Tobacco smoking was identified as increasing PCa risks in Europeans (odds ratio [OR]: 1.95, 95% confidence interval [CI]: 1.09–3.50, p = 0.027 per standard deviation increase in the lifetime smoking index). For East Asians, alcohol drinking (OR: 1.05, 95%CI: 1.01–1.09, p = 0.011) and delayed sexual initiation (OR: 1.04, 95%CI: 1.00–1.08, p = 0.029) were identified as risk factors, while cooked vegetable consumption (OR: 0.92, 95%CI: 0.88–0.96, p = 0.001) was a protective factor for PCa. Conclusions: Our findings broaden the evidence base for the spectrum of PCa risk factors in different ethnicities, and provide insights into behavioral interventions for prostate cancer.