Head-to-head Comparison of Conventional, and Image- and Biomarker-based Prostate Cancer Risk Calculators.

BACKGROUND: A new generation of risk calculators (RCs) for prostate cancer (PCa) incorporating magnetic resonance imaging (MRI) data have been introduced. However, these have not been validated externally, and their clinical benefit compared with alternative approaches remains unclear. OBJECTIVE: To assess previously published PCa RCs incorporating MRI data, and compare their performance with traditional RCs (European Randomized Study of Screening for Prostate Cancer [ERSPC] 3/4 and Prostate Biopsy Collaborative Group [PBCG]) and the blood-based Stockholm3 test. DESIGN, SETTING, AND PARTICIPANTS: RCs were tested in a prospective multicenter cohort including 532 men aged 45-74 yr participating in the Stockholm3-MRI study between 2016 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The probabilities of detection of clinically significant PCa (csPCa) defined as Gleason score ≥3 + 4 were calculated for each patient. For each RC and the Stockholm3 test, discrimination was assessed by area under the curve (AUC), calibration by numerical and graphical summaries, and clinical usefulness by decision curve analysis (DCA). RESULTS AND LIMITATIONS: The discriminative ability of MRI RCs 1-4 for the detection of csPCa was superior (AUC 0.81-0.87) to the traditional RCs (AUC 0.76-0.80). The observed prevalence of csPCa in the cohort was 37%, but calibration-in-the-large predictions varied from 14% to 63% across models. DCA identified only one model including MRI data as clinically useful at a threshold probability of 10%. The Stockholm3 test achieved equivalent performance for discrimination (AUC 0.86) and DCA, but was underpredicting the actual risk. CONCLUSIONS: Although MRI RCs discriminated csPCa better than traditional RCs, their predicted probabilities were variable in accuracy, and DCA identified only one model as clinically useful. PATIENT SUMMARY: Novel risk calculators (RCs) incorporating imaging improved the ability to discriminate clinically significant prostate cancer compared with traditional tools. However, all but one predicted divergent compared with actual risks, suggesting that regional modifications be implemented before usage. The Stockholm3 test achieved performance comparable with the best MRI RC without utilization of imaging.

Biomarker discrimination and calibration with MRI-targeted biopsies: an analysis with the Stockholm3 test.

BACKGROUND: The validated Stockholm3 test is used to improve PC detection. Stockholm3, however, was developed using systematic biopsies. We aimed to assess Stockholm3 operating performance when using MRI-targeted biopsies for PC detection. METHODS: A prospective cohort of 532 men was considered for prostate biopsy during 2016-2017. All men underwent Stockholm3 testing and MRI before biopsy. All PIRADs ≥3 lesion underwent targeted biopsy; all men underwent systematic biopsy. The primary outcome was ISUP Grade Group ≥2 (GG ≥ 2) PC. Detection strategies included: (1) systematic biopsies alone, (2) targeted biopsies alone, (3) targeted with associated systematic biopsies for MRI+, and (4) all biopsies in all men. For each strategy, the Stockholm3 operating characteristics were assessed with discrimination, calibration, and decision curve analysis (DCA). RESULTS: Median age was 65 years, median PSA was 6.2 ng/mL, median Stockholm3 score was 16.5%, and overall detection of GG ≥ 2 PC was 36% (193/532). Stockholm3 showed accurate discrimination for separating GG ≥ 2 cancer from benign and GG1, with an area under the curve of 0.84-0.86 depending on the biopsy strategy. Calibration analysis showed that Stockholm3 underestimated risks for GG ≥ 2 PC risk using MRI-targeted biopsies: there was a net benefit over biopsies in all men for Stockholm3 at risk thresholds varying from >3% in systematic biopsies to >15% in targeted with systematic biopsies in MRI+ men. When using a Stockholm3 score of >10% cutoff, a range of 32-38% of biopsies could be avoided while missing 5-11% of GG ≥ 2 PC and 0-3% of GG ≥ 3 PC. CONCLUSIONS: Stockholm3 shows high discriminatory performance in an MRI-targeted biopsy setting, however risks are underpredicted due to MRI-targeted biopsies being more sensitive than the systematic biopsies for which Stockholm3 was developed. Stockholm3, along with any risk prediction model developed for systematic prostate biopsy decisions, will need recalibration for optimal use in an MRI-driven biopsy setting.

Work status and work ability after radical prostatectomy or active surveillance for prostate cancer.

Objective: Being able to work is important for health-related quality of life (HRQoL), and little is known about work life after radical treatment for prostate cancer (PCa). The aim was to investigate work status (WS) and work ability (WA) after radical prostatectomy (RP) or active surveillance (AS) for PCa, and to identify factors associated with reduced WA.Materials and methods: This is a retrospective cross-sectional study of 606 men treated with RP (n = 442) or AS (n = 164) at two Norwegian general hospitals. In 2017, they were asked to complete questionnaires measuring adverse effects (AE), HRQoL, aspects of work life and psychological factors at a median of 4.1 (range 1.3-8.1) years after diagnosis. Clinical data were retrieved from medical records. WS was categorized into employed, unemployed or retired. WA was rated using the Work Ability Index. Regression analyses were performed to find factors associated with reduced WA.Results: WS was similar for the RP and AS groups at diagnosis and survey. There was a small reduction in WA from diagnosis to survey and the difference between the RP and AS groups was non-significant. Older age, poorer self-rated health, poorer incontinence score, more chronic fatigue, and increased anxiety and depressive symptoms were associated with reduced WA, while treatment method, urinary bother and use of pads were not.Conclusion: The impact of RP and AS on WS and WA was almost similar. Age and psychological variables were more strongly associated with reduced WA than cancer-related variables.

Health-related quality-of-life after radical cystectomy among Norwegian men and women compared to the general population.

Objective: The aim of this study was to assess health-related quality-of-life (HRQoL) in men and women operated on with radical cystectomy, compared to the general Norwegian population.Materials and methods: All patients with bladder cancer who had undergone radical cystectomy (RC) between 2011-2017 and either received ileal conduit (IC) or orthotopic neobladder (ONB) as urinary diversion were included in a cross-sectional study. HRQoL and sociodemographic data was collected and measured with a questionnaire consisting of the generic EORTC QLQ-C30.v3 and the cancer specific EORTC QLQ-BLM30 and compared to a general population sample.Results: Of the 220 invited patients, 173 patients (78.6%) returned the questionnaires. The global quality-of-life (QoL) score was comparable with the general population. Women had significantly higher fatigue score, worse future perspective and symptoms like bloating, compared to male patients. Men had significantly lower social functioning, more constipation, diarrhoea and sleep disturbance compared to the general male population. There was no significant difference in HRQoL domains between female patients and the general female population. A follow-up (FU) period longer than 37 months since surgery was associated with significantly improved physical- and role-functioning, less fatigue and fewer problems with the urostoma, compared to a shorter FU time.Conclusion: This study found a high global QoL score after radical cystectomy, comparable with the general Norwegian population. Symptoms seem to improve over time. Difference in HRQoL outcomes between men and woman in the study population was comparable with the difference found in the general population.

Non-metastatic prostate cancer: rationale for conservative treatment and impact on disease-related morbidity and mortality in the elderly.

Purpose: To determine the rationale for not offering local treatment to prostate cancer patients with non-metastatic disease at diagnosis who later died of prostate cancer and to document local and systemic complications caused by disease progression.Material and Methods: In this population-based, retrospective study we reviewed the medical records of all patients who died of prostate cancer in 2009-2014 in Vestfold County (Vestfold Mortality Study), who were non-metastatic at diagnosis and who had received no local treatment to the prostate (n = 117).Results: A review of patient records demonstrated that the chronological age of 75 years or older was the main rationale for not offering local treatment to the prostate (37%, n = 43). No consideration was given to the functional status and patient health. These elderly patients stood for almost one-fifth of the total PC mortality in Vestfold County. In addition to dying from PC, 86% of patients developed local complications attributable to PC progression. Observation of strict limits for local treatment with regard to tumor characteristics contributed further to the underuse of local treatment.Conclusions: Our study demonstrated systematic undertreatment of elderly patients with aggressive, non-metastatic PC with regard to local treatment based on chronological age alone. The patients in this study died of prostate cancer and the majority experienced significant morbidity caused by local tumor growth.

Crude mortality and loss of life expectancy of patients diagnosed with urothelial carcinoma of the urinary bladder in Norway.

OBJECTIVE: Reports from cancer registries often lack clinically relevant information, which would be useful in estimating the prognosis of individual patients with urothelial carcinoma of the urinary bladder (UCB). This article presents estimates of crude probabilities of death due to UCB and the expected loss of lifetime stratified for patient characteristics. MATERIALS AND METHODS: In Norway, 10,332 patients were diagnosed with UCB between 2001 and 2010. The crude probabilities of death due to UCB were estimated, stratified by gender, age and T stage, using flexible parametric survival models. Based on these models, the loss in expectation of lifetime due to UCB was also estimated for the different strata. RESULTS: There is large variation in the estimated crude probabilities of death due to UCB (from 0.03 to 0.76 within 10 years since diagnosis) depending on age, gender and T stage. Furthermore, the expected loss of life expectancy is more than a decade for younger patients with muscle-invasive UCB and between a few months and 5 years for nonmuscle-invasive UCB. CONCLUSIONS: The suggested framework leads to clinically relevant prognostic risk estimates for individual patients diagnosed with UCB and the consequence in terms of loss of lifetime expectation. The published probability tables can be used in clinical praxis for risk communication.

"Natural course" of disease in patients with metastatic castrate-resistant prostate cancer: Survival and prognostic factors without life-prolonging treatment.

OBJECTIVE: The aim of this study was to determine survival and prognostic factors in unselected patients with metastatic castrate-resistant prostate cancer (mCRPC), who never received life-prolonging treatment. MATERIALS AND METHODS: The study was a retrospective analysis of a consecutive sample of patients with mCRPC seen at the urological unit of a local hospital from 2000 to 2005, their mCRPC diagnosis based on rising prostate-specific antigen (PSA) during androgen depletion treatment (ADT). RESULTS: Median overall survival was 12.3 months (range 0.2-108 months), the 3 year survival was 16.9% (95% confidence interval 0.11-0.24) and two patients were alive at the end of follow-up. Compared to a PSA nadir of greater than 11 µg/l during ADT, a PSA nadir of less than 1 µg/l significantly decreased the risk of death by 71%. A PSA doubling time less than 1.6 months during the early phase of mCRCP almost tripled the risk of death compared to a PSA doubling time longer than 3 months. Alkaline phosphatase serum levels and hemoglobin levels within the normal range indicated a favorable prognosis. CONCLUSIONS: The "natural course" of mCRPC varies without life-prolonging treatment along with PSA nadir during ADT, PSA doubling time, alkaline phosphatase and hemoglobin level at mCRPC diagnosis. 3-year survival or longer is observed in 16.9% of patients. In clinical intervention trials among mCRPC patients, all known prognostic factors should be taken into account during the randomization process and during survival analyses.

Improved long-term survival following infrarenal abdominal aortic aneurysm repair.

BACKGROUND: The aim was to investigate early and long-term results following AAA repair during a 20-year period. METHOD: One thousand and forty one patients with AAA were treated with open surgery (905) or EVAR (136) during the period 1983-2002. Comorbidity and factors influencing early and long-term results were investigated. Data were collected retrospectively from the patients' medical records. A complete follow-up was obtained. RESULTS: Women had a significantly higher 30-day mortality following repair of ruptured AAA than men. The degree of emergency, advancing age and renal failure were significantly associated with 30-day mortality. We observed an improvement in long-term survival during the study period. Time interval of surgery, cerebrovascular disease, diabetes, COPD and renal failure influenced long-term survival negatively. CONCLUSION: Women with ruptured AAA have a higher early mortality than men, which needs to be investigated further. Long-term survival has improved during the study period. Age, diabetes, chronic obstructive pulmonary disease, renal failure and cerebrovascular insufficiency influenced the long-term survival negatively. EVAR is used to an increasing extent and the results are improving.

Infrarenal abdominal aortic aneurysm repair: time-trends during a 20-year period.

BACKGROUND: The goal of the present study was to investigate the number of operations for abdominal aortic aneurysm (AAA) including time-trends in treatment during a 20-year period. Operating time and anesthesia time were also studied. METHOD: During the period 1983-2002, a total of 1,041 patients with AAA were treated with open surgery (905) or EVAR (136). Number of operations, type of graft, anesthesia time, and operating time were the variables investigated. Data were collected retrospectively from the patients' medical records. RESULTS: There was an increase in the number of operations both for ruptured and non-ruptured AAA in men during the study period. Among women, an increase was observed only for ruptured aneurysm. Operating time and anesthesia time increased significantly during the 20-year period. The number of patients treated by EVAR increased significantly, beginning in 1995. CONCLUSIONS: In conclusion, there has been an increase in the number of AAA operations, and the proportion of patients treated with EVAR is increasing. Furthermore, we found an increase in both anesthesia time and operating time. These trends may be important for allocation of resources needed for the treatment of patients with AAA.