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Background and objective

Prognostication is a cornerstone of the clinical management of prostate cancer. This study aims to update the pre- and postoperative Memorial Sloan Kettering Cancer Center (MSKCC) nomograms for the prediction of 10-yr prostate cancer–specific mortality in the competing risk setting in Sweden, and to evaluate the added value of comorbidities.

Methods

A cohort study was conducted including all men in the National Prostate Cancer Register of Sweden diagnosed with localised prostate cancer in 2007–2020, who underwent radical prostatectomy. Follow-up was until December 31, 2022. We used cause-specific Cox proportional hazard models to obtain the cumulative incidence of prostate cancer–specific and other-cause mortality. The models were validated in terms of discrimination (concordance [C] index) and calibration by internal-external validation in six Swedish health care regions and by bootstrapping (N = 500).

Key findings and limitations

The cohort included 31 106 men, of whom 629 died from prostate cancer and 2415 died from other causes during a median follow-up of 8.3 yr (interquartile range: 5.2, 11.8). Comorbidities added more value to the other-cause mortality model than to the prostate cancer–specific mortality model, and were included in all models. Both the preoperative and the postoperative model showed high discrimination for prostate cancer–specific death (optimism-corrected C-index: 0.81 and 0.87, respectively), but not for other-cause mortality (0.67, both models). All models were well calibrated, with minimal overestimation at the higher range of predicted cumulative incidences for the preoperative, but not for the postoperative, model.

Conclusions and clinical implications

The updated MSKCC nomograms performed well in terms of discrimination and calibration, and can be used in clinical practice in Sweden. In this study, comorbidity added minimal prognostic value for predicting prostate cancer–specific mortality. External validation is advised for application in other populations.

Patient summary

Prognostication is a cornerstone in the clinical management of prostate cancer. In this study, we adapted the best preforming risk classification system, the pre- and postoperative Memorial Sloan Kettering Cancer Center nomograms, for the prediction of prostate cancer–specific death in Swedish setting. The adapted models perform well and can be applied directly to Swedish men with prostate cancer.

Prostate cancer grade is currently often reported both by Gleason scores and by grouping of the scores into five socalled International Society of Urological Pathology (ISUP) grades (also known as grade groups). Using population-based registry data from 172,112 men diagnosed with prostate cancer on needle biopsy, we recently investigated the outcome of Gleason score 8-10 prostate cancer with death due to prostate cancer and death from any cause as endpoints. There was a prognostic heterogeneity between Gleason scores 3+5, 4+4 and 5+3 (ISUP grade 4) and between Gleason scores 4+5, 5+4 and 5+5 (ISUP grade 5). This heterogeneity was lost when the grades collapsed into ISUP grades 4 and 5, respectively. On the other hand, there was also a prognostic overlap between these ISUP grades. The outcome of Gleason score 5+3 and 4+5 cancers was very similar. The prostatespecific mortality of Gleason scores 5+3 and 4+5 was 0.32 (95% confidence interval 0.27-0.36) and 0.30 (0.29-0.31), respectively, after 5 years and 0.44 (0.39-0.49) and 0.45 (0.44-0.46), respectively, after 10 years. The findings emphasise the importance of reporting the Gleason grades and scores for more accurate prognostic information of highly heterogeneous high-grade prostate cancers. It also questions the clinical value of the current recommendations of grouping of Gleason scores into ISUP grades or grade groups.

Background: There has been a wide range in incidence of prostate-specific antigen (PSA) persistence and relapse after radical prostatectomy (RP) for prostate cancer (PCa). We aimed to describe incidence and prognostic implications of PSA persistence and relapse.

Methods: Register-based cohort study in Sweden of men diagnosed with PCa between 2007 and 2020 who underwent RP. Risks were estimated using competing risk cumulative incidence curves. Treatment after persistence or relapse and risk of PCa death and other causes were stratified according to persistence, European Association of Urology relapse risk groups, time to relapse, and life expectancy based on age and comorbidities.

Results: Among 10 700 men, the 10-year risk of PSA persistence or relapse after RP was 34% (95% confidence interval = 32% to 35%). Within 12 months of persistence/relapse, 75% of men with persistence, high-risk relapse, or early relapse (<2 years) received treatment. The 10-year risk of PCa death ranged from 12% for men with persistence to 2% in men with low-risk relapse, whereas death from other causes ranged from 11% to 16%. Risk of PCa death was 8.5% after early relapse (<2 years) and 1.4% after late relapse (>5 years).

Conclusions: This population-based study estimated that one-third of men would have PSA persistence or relapse within 10 years from RP. There was a wide range in risk of death from PCa according to cancer characteristics and time to relapse. Risk of death from other causes was substantial. These factors, along with life expectancy, should inform treatment decisions for men with persistence or relapse.

Background: Data on long-term outcomes for men with prostate cancer treated according to current guidelines are limited. We aimed to estimate the long-term risk of death from prostate cancer and other causes in men with nonmetastatic prostate cancer who received primary treatment according to current guidelines.

Methods: Men with nonmetastatic prostate cancer registered in the National Prostate Cancer Register of Sweden from 2000 to 2020, who received primary treatment according to NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer, Version 4.2023, were included and followed until December 31, 2022. The risk of death from prostate cancer and other causes up to 30 years was estimated according to risk category and life expectancy using a state transition simulation model.

Results: A total of 62,839 men received primary treatment according to the NCCN Guidelines. The simulated 15-year prostate cancer mortality per risk category ranged from 5.5% (95% CI, 4.8%-6.2%) in men with low-risk cancer to 22% (95% CI, 21%-24%) in men with very high-risk cancer. Simulated 30-year prostate cancer mortality ranged from 12% (95% CI, 10%-14%) in men with low-risk cancer to 30% (95% CI, 29%-32%) in men with very high-risk cancer, whereas death from other causes ranged from 77% (95% CI, 74%-80%) to 63% (95% CI, 59%-67%), respectively.

Conclusions: Men with nonmetastatic prostate cancer who received primary treatment according to current guidelines were up to 6 times more likely to die of other causes than from their cancer. These estimates provide realistic but high expectations of the outcomes of modern treatment and can serve as benchmarks for clinical outcome reporting.

Objectives

To investigate the impact of age and life expectancy on treatment decisions and its consequences for outcomes among men with intermediate and high-risk prostate cancer (PCa).

Materials and methods

We studied men in Prostate Cancer data Base Sweden (PCBaSe) diagnosed between 2008 and 2022 with intermediate-risk or high-risk localized or locally advanced PCa and life expectancy between 2.5 and 15 years in the absence of PCa. Estimates of life expectancy were based on age and two comorbidity indices.

Results

A total of 32 196 men were included in the analyses. Of these, 17 419 (54%) had a life expectancy between 10 and 15 years, of whom 11 147 (64%) received primary radical treatment. Age had a stronger influence than life expectancy on the selection of treatment. Around 10% of deaths within 10 years of diagnosis could potentially have been avoided if men with >10 years life expectancy, regardless of age, had received radical treatment, based on assumptions of high treatment efficacy (30% reduction in all-cause mortality) and high uptake of treatment (90%).

Conclusion

A substantial proportion of healthy older men with intermediate and high-risk PCa did not undergo radical treatment. According to our model and assumptions, 10% of deaths within 10 years of diagnosis in these men could potentially have been avoided if they had received radical treatment.

Background: The role and optimal sequencing of radium-223 in the treatment of metastatic castration-resistant prostate cancer (mCRPC) remain debated. In Europe, radium-223 is restricted to third line treatment or later for chemotherapy-eligible men, although studies suggest greater benefit with earlier use. In this nationwide, population-based study, we investigated radium-223 use in Sweden and analyzed the association between line of treatment and overall survival.

Methods: Men with mCRPC who started radium-223 in 2014-2020 were identified in national registers. The Kaplan-Meier method was used to estimate survival. The association between line of treatment and survival was analyzed with Cox regression and presented as adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). A subgroup with at least three mCRPC treatment lines was similarly analyzed.

Results: 1,133 men were included. Median overall survival was 13.9 months (95% CI 13.0-14.5). Later line of radium-223 treatment was associated with shorter survival; with first line as reference, aHR for death for second line was 1.34 (95% CI 1.12-1.59) and for third line 1.55 (1.29-1.87). The opposite was observed for 596 men with at least three lines of mCRPC treatment: aHR for second line was 0.80 (0.59-1.08) and for third line 0.78 (0.59-1.03).

Interpretation: Survival after start of radium-223 in Sweden was comparable to pivotal trials, suggesting effective use. Our overall results do not suggest a better effect of radium-223 in first versus later mCRPC treatment lines but rather emphasize the value of a randomized controlled trial to more definitely determine the optimal timing of radium-223 treatment.

Background: Inequity in prostate cancer detection can be assessed by relating the diagnostic intensity to the incidence rate of advanced disease in different population groups, according to factors such as socioeconomic status or ethnicity.

Methods: We used nationwide Swedish register data from Prostate Cancer data Base Sweden 5.0 and Statistics Sweden, which enabled us to estimate incidence rates of low-risk prostate cancer (a proxy for diagnostic activity) and advanced disease (locally advanced and/or metastatic) across population groups according to household income, country of birth, and neighborhood-level characteristics.

Results: We found a gradient in the age-standardized incidence of low-risk prostate cancer across income groups, from 60 per 100,000/year in men with high to 34 per 100,000/year in men with low household income: adjusted incidence rate ratio (IRR) 0.65 (95% confidence interval [CI] 0.59–0.71). The gradient in the incidence of advanced disease had the opposite direction, from 44 to 60 per 100,000/year, IRR 1.43 (95% CI 1.31–1.56). Immigrants from a non-Nordic country (nearly 40% from Asia) had lower incidence rates of both low-risk (IRR 0.47, 95% CI 0.42–0.53) and advanced disease (IRR 0.65, 95% CI 0.58–0.73) than men born in a Nordic country. Neighborhood-level analysis considering economic standard, share of immigrants, and degree of urbanization did not clearly differentiate the incidence of advanced disease.

Interpretation: Our results suggest that measures to facilitate early detection of prostate cancer should be targeted to men with a low income. A low diagnostic activity for prostate cancer among immigrants from countries with low background risk may not imply unjustified social disparity.