Repeated Prostate Cancer Screening Using Prostate-Specific Antigen Testing and Magnetic Resonance Imaging: A Secondary Analysis of the STHLM3-MRI Randomized Clinical Trial.

Importance: Magnetic resonance imaging (MRI) has been proposed to enhance the benefit-to-harm ratio of prostate cancer screening, but data on repeated screening outcomes are lacking. Objective: To describe outcomes of prostate-specific antigen (PSA)-based screening with MRI and prostate biopsies at repeat screening. Design, Setting, and Participants: This secondary analysis examined the population-based, screen-by-invitation STHLM3-MRI randomized clinical trial, which recruited Swedish men aged 50 to 74 years. Men were eligible for repeat screening at 2 to 3 years if they had PSA levels of 1.5 ng/mL or greater at trial inclusion, were randomized to the MRI-targeted group (including screening using biomarkers and MRI), and were not diagnosed with prostate cancer after the first screening round. Repeat screening was performed between November 10, 2021, and February 20, 2023. Data analysis was performed between May and August 2023. Intervention: Participants underwent blood sampling, including PSA testing. A biparametric MRI scan was performed if PSA levels were 3 ng/mL or greater, and men with lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3 or greater were referred for targeted and systematic biopsies. Main Outcomes and Measures: The primary outcome was clinically significant prostate cancer (Gleason score of ≥3 + 4). Secondary outcomes included the proportion of men with clinically insignificant cancer (Gleason score of 6), the number of elevated PSA tests, MRI scans, and biopsy procedures. Results: Of 7609 men from the first screening round, 2078 (27.3%) were eligible for and were invited for rescreening. Among the invitees, 1500 (72.2%) participated. Their median age was 67 (IQR, 61-72) years. Of 1094 men with PSA levels between 1.5 and 2.9 ng/mL in the first screening round, 326 (29.8%) had levels of 3 ng/mL or greater in the second round. Overall, 667 men (44.5%) had PSA levels of 3 ng/mL or greater: 617 underwent MRI (92.5%), revealing 51 (7.6%) with equivocal lesions (PI-RADS score of 3) and 33 (4.9%) with suspicious lesions (PI-RADS score of ≥4). Only 10 of 383 men (2.6%) with a prior negative MRI result had a lesion with a PI-RADS score of 4 or greater. Among the 1500 rescreened men, 48 (3.2%) had a Gleason score of 3 + 4 or greater, including 19 (1.3%) with a score of 4 + 3 or greater and 11 (0.7%) with a score of 6. Conclusions and Relevance: In this secondary analysis of the STHLM3-MRI randomized clinical trial, cancer detection during the second screening round in biennial PSA and MRI-based prostate cancer screening was limited, and the detection of low-grade tumors remained low. A substantial proportion of men exhibited elevated PSA levels during rescreening, and a considerable portion of MRI scans performed lacked lesions suggestive of cancer. Future studies should explore strategies to reduce MRI-related resource use. Trial Registration: ClinicalTrials.gov Identifier: NCT03377881.

Biochemical Recurrence and Risk of Mortality Following Radiotherapy or Radical Prostatectomy.

Importance: Stratifying patients with biochemical recurrence (BCR) after primary treatment for prostate cancer based on the risk of prostate cancer-specific mortality (PCSM) is essential for determining the need for further testing and treatments. Objective: To evaluate the association of BCR after radical prostatectomy or radiotherapy and its current risk stratification with PCSM. Design, Setting, and Participants: This population-based cohort study included a total of 16 311 male patients with 10 364 (64%) undergoing radical prostatectomy and 5947 (36%) undergoing radiotherapy with curative intent (cT1-3, cM0) and PSA follow-up in Stockholm, Sweden, between 2003 and 2019. Follow-up for all patients was until death, emigration, or end of the study (ie, December 31, 2018). Data were analyzed between September 2022 and March 2023. Main Outcomes and Measures: Primary outcomes of the study were the cumulative incidence of BCR and PCSM. Patients with BCR were stratified in low- and high-risk according to European Association of Urology (EAU) criteria. Exposures: Radical prostatectomy or radiotherapy. Results: A total of 16 311 patients were included. Median (IQR) age was 64 (59-68) years in the radical prostatectomy cohort (10 364 patients) and 69 (64-73) years in the radiotherapy cohort (5947 patients). Median (IQR) follow-up for survivors was 88 (55-138) months and 89 (53-134) months, respectively. Following radical prostatectomy, the 15-year cumulative incidences of BCR were 16% (95% CI, 15%-18%) for the 4024 patients in the low D'Amico risk group, 30% (95% CI, 27%-32%) for the 5239 patients in the intermediate D'Amico risk group, and 46% (95% CI, 42%-51%) for 1101 patients in the high D'Amico risk group. Following radiotherapy, the 15-year cumulative incidences of BCR were 18% (95% CI, 15%-21%) for the 1230 patients in the low-risk group, 24% (95% CI, 21%-26%) for the 2355 patients in the intermediate-risk group, and 36% (95% CI, 33%-39%) for the 2362 patients in the high-risk group. The 10-year cumulative incidences of PCSM after radical prostatectomy were 4% (95% CI, 2%-6%) for the 1101 patients who developed low-risk EAU-BCR and 9% (95% CI, 5%-13%) for 649 patients who developed high-risk EAU-BCR. After radiotherapy, the 10-year PCSM cumulative incidences were 24% (95% CI, 19%-29%) for the 591 patients in the low-risk EAU-BCR category and 46% (95% CI, 40%-51%) for the 600 patients in the high-risk EAU-BCR category. Conclusions and Relevance: These findings suggest the validity of EAU-BCR stratification system. However, while the risk of dying from prostate cancer in low-risk EAU-BCR after radical prostatectomy was very low, patients who developed low-risk EAU-BCR after radiotherapy had a nonnegligible risk of prostate cancer mortality. Improving risk stratification of patients with BCR is pivotal to guide salvage treatment decisions, reduce overtreatment, and limit the number of staging tests in the event of PSA elevations after primary treatment.

Waterpipe Nicotine Dependence and Depressive Symptoms among Adolescent Waterpipe and Dual Users.

Background: Waterpipe nicotine dependence and its association with depressive symptoms and dual usage among adolescents are currently not examined in the literature. Adolescents are a vulnerable population that is susceptible to depression and initiation of tobacco use. We aim, in this novel study, to assess the association between depressive symptoms and waterpipe nicotine dependence among adolescents in Jordan, evaluate the association between waterpipe smoking status (waterpipe smoker vs. dual user) and waterpipe nicotine dependence, and assess the internal validity of the Waterpipe Nicotine Dependence Scale (WNDS). Method: A cross-sectional study among adolescents of grade 9th to 12th in Jordan was conducted through multistage cluster random sampling. The self-reported Arabic Youth Tobacco Use Composite Measure Questionnaire (YTUCM) was used to collect the surveys that include demographic information, smoking status, and the WNDS to assess waterpipe nicotine dependence and depressive symptoms. Multiple linear regression and the t-test were used to analyze the data. Findings. One thousand three hundred and three surveys were collected, of which 1082 were included in the study (443 males and 639 females). 64.9% of the sample were nontobacco users, while 20.1% were waterpipe- (WTP-) only smokers, 11.4% were dual users, and 3.7% were cigarettes-only users. After adjusting for weights, 66.6% were nonsmokers, 19.2% were WTP-only smokers, 10.2% were dual users, and 3.9% were cigarettes-only smokers. Using multiple linear regression, depressive symptoms were significantly associated with WTP nicotine dependence (ß 0.618), upon adjusting for confounders. Furthermore, dual users were associated with higher WTP nicotine dependence (ß 12.034) compared to WTP-only smokers after adjusting for confounders. Cronbach's alpha for the WNDS was 0.955. Conclusions: Our study shows that there is a statistically significant association between depressive symptoms and WTP nicotine dependence and higher dependence among dual users compared to WTP-only smokers. The WNDS can be a useful tool to assess WTP nicotine dependence with high internal consistency. However, a longitudinal study is needed to further understand the association and temporality between the depressive symptoms and WTP nicotine dependence. Additionally, research is needed to shorten the WNDS while maintaining high internal consistency and assess the external validity of the WNDS and the short- and long-term consequences of dual usage.