Expected population impacts of discontinued prostate‐specific antigen screening

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109652/1/cncr28932-sup-0001-suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109652/2/cncr28932.pd

Characteristics of screen-failures in prostate cancer screening

ABSTRACT Although prostate-specific antigen (PSA)-based screening has been shown to reduce prostate cancer (PC)-specific mortality with large variations in mortality reduction with different screening algorithms, the optimal screening strategy has not yet been established. This thesis aims at exploring aspects of underdiagnosis in PC screening, focusing on the impact of screening failures on screening effectiveness. All of its papers are based on the Göteborg randomized PC screening trial except for Paper I, which also includes data from the Dutch center of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Paper I analyzes the frequency of interval cancers (IC) between a 2- and a 4-year screening interval, as high IC rates are recognized as a limitation for screening effectiveness in screening for other cancers. Extremely few IC cases were detected and no difference was found in cumulative incidences of IC with a 2- and 4-year interval. In Paper II, the risk of PC death is compared between attendees and nonattendees in screening. A large proportion of PC deaths occurred in nonattendees, and the majority of attendees dying from PC were men aged ≥60 years when detected at their first (prevalence) screen. Paper III analyzes the PC incidence after screening cessation (due to upper age limit). Compared to the control arm, the incidence of potentially aggressive PC was reduced in the screening arm up to 9 years post-screening but thereafter approached the incidence of the control group. In Paper IV, multiparametric magnetic resonance imaging (mpMRI) was evaluated as a screening tool. A lowered PSA cut-off (1.8 ng/ml) + mpMRI followed by targeted biopsy yielded a higher detection rate of clinically significant PC compared with “conventional” screening (PSA, cut-off ≥3 ng/ml followed by systematic biopsy), requiring a decreased number of biopsies. In conclusion, better screening strategies are needed to improve on screening failures. One option may be to lower the PSA cut-off and introduce sequential testing with mpMRI to decide which men to refer for biopsy. Age at screening start and cessation greatly impacts efficiency; starting at age 60 is probably too late, and stopping at age 70 for all men is probably too early

End-stage renal disease after renal cancer surgery : risk factors and overall survival

OBJECTIVE: Several risk factors for end-stage renal disease (ESRD), in patients undergoing surgical treatment for renal cell carcinoma (RCC), have been suggested by others. This study aimed to investigate such risk factors and disclose the effect of developing ESRD, postoperatively, on overall survival. The risk of developing ESRD after RCC diagnosis was also evaluated. MATERIAL AND METHODS: The data of 16,220 patients with RCC and 162,199 controls were extracted from the Renal Cell Cancer Database Sweden, with linkages across multiple national registers between 2005 and 2020. Cox proportional hazards regression, Kaplan-Meier curves and cumulative incidence were used for statistical analysis. RESULTS: The 5-year cumulative incidence of ESRD following RCC diagnosis was 2.4% (95% confidence interval [CI] 2.1-2.6) and 0.4% (95% CI 0.3-0.4) for the patients with RCC and controls, respectively. Age, chronic kidney disease, higher T-stage and radical nephrectomy (RN) were significant risk factors for ESRD within 1-year of surgery. A total of 104 and 12,152 patients with and without ESRD, respectively, survived 1-year postoperatively. The 5-year overall survival rates of patients with ESRD and those with RCC only were 50% (95% CI 0.40-0.60) and 80% (95% CI 0.80-0.81), respectively. CONCLUSIONS: Patients who developed ESRD following renal cancer surgery had significantly poorer survival outcomes. Advanced age, comorbidities, higher-stage tumours and RN were identified as risk factors for developing ESRD. Surgical decisions are crucial. Efforts to spare renal function, including nephron-sparing surgery and active surveillance in appropriate cases, are highly relevant to reduce the development of severe kidney dysfunction

Predictors for complication in renal cancer surgery : a national register study

OBJECTIVE: Nationwide register data provide unique opportunities for real-world assessment of complications from different surgical methods. This study aimed to assess incidence of, and predictors for, post-operative complications and to evaluate 90-day mortality  following different surgical procedures and thermal ablation for renal cell carcinoma (RCC). MATERIAL AND METHODS: All patients undergoing surgical treatment and thermal ablation for RCC in Sweden during 2015-2019 were identified from the National Swedish Kidney Cancer Register. Frequencies and types of post-operative complications were analysed. Logistic regression models were used to identify predictors for 90-day major (Clavien-Dindo grades III-V) complications, including death. RESULTS: The overall complication rate was 24% (1295/5505), of which 495 (8.7%) were major complications. Most complications occurred following open surgery, of which bleeding and infection were the most common. Twice as many complications were observed in patients undergoing open surgery compared to minimally invasive surgery (20% vs. 10%, P < 0.001). Statistically significant predictors for major complications irrespective of surgical category and technique were American society of anesthiologists (ASA) score, tumour diameter and serum creatinine. Separating radical and partial nephrectomy, surgical technique remained a significant risk factor for major complications. Most complications occurred within the first 20 days. The overall 90-day readmission rate was 6.2%, and 30- and 90-day mortality rates were 0.47% and 1.5%, respectively. CONCLUSIONS: In conclusion, bleeding and infection were the most common major complications after RCC surgery. Twice as many patients undergoing open surgery suffer a major post-operative complication as compared to patients subjected to minimally invasive surgery. General predictors for major complications were ASA score, tumour size, kidney function and surgical technique

Eighteen-year follow-up of the Göteborg Randomized Population-based Prostate Cancer Screening Trial : effect of sociodemographic variables on participation, prostate cancer incidence and mortality

Objective: This study examined whether previously reported results, indicating that prostate-specific antigen (PSA) screening can reduce prostate cancer (PC) mortality regardless of sociodemographic inequality, could be corroborated in an 18 year follow-up. Materials and methods: In 1994, 20,000 men aged 50–64 years were randomized from the Göteborg population register to PSA screening or control (1:1) (study ID: ISRCTN54449243). Men in the screening group (n = 9950) were invited for biennial PSA testing up to the median age of 69 years. Prostate biopsy was recommended for men with PSA ≥2.5 ng/ml. Last follow-up was on 31 December 2012. Results: In the screening group, 77% (7647/9950) attended at least once. After 18 years, 1396 men in the screening group and 962 controls had been diagnosed with PC [hazard ratio 1.51, 95% confidence interval (CI) 1.39–1.64]. Cumulative PC mortality was 0.98% (95% CI 0.78–1.22%) in the screening group versus 1.50% (95% CI 1.26–1.79%) in controls, an absolute reduction of 0.52% (95% CI 0.17–0.87%). The rate ratio (RR) for PC death was 0.65 (95% CI 0.49–0.87). To prevent one death from PC, the number needed to invite was 231 and the number needed to diagnose was 10. Systematic PSA screening demonstrated greater benefit in PC mortality for men who started screening at age 55–59 years (RR 0.47, 95% CI 0.29–0.78) and men with low education (RR 0.49, 95% CI 0.31–0.78). Conclusions: These data corroborate previous findings that systematic PSA screening reduces PC mortality and suggest that systematic screening may reduce sociodemographic inequality in PC mortality