Outcomes of Biopsy Grade Group 1 Prostate Cancer Diagnosis in the Danish Population.

BACKGROUND: Debate regarding a nomenclature change for grade group 1 (GG 1) prostate cancer to noncancer has been revived, as this could be a powerful tool in reducing the overtreatment of indolent disease. OBJECTIVE: To describe outcomes for all men diagnosed with GG 1 prostate cancer in the Danish population, with a focus on men followed conservatively. DESIGN, SETTING, AND PARTICIPANTS: This was a population-based observational study using data from the Danish Prostate Registry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured the cumulative incidence of curative treatment, endocrine treatment, and cause-specific mortality. RESULTS AND LIMITATIONS: The cumulative incidence of endocrine therapy at 10 yr was 5.3% (95% confidence interval [CI] 4.3-6.3%) for men with initial active surveillance and 21% (95% CI 19-23%) for men with initial watchful waiting for localized GG 1. In the GG1 cohort, the prostate cancer-specific mortality rate at 15 yr was 14% (95 CI% 11-16%) for men on watchful waiting, 10% (95 CI% 6.7-14%) for men with prostate-specific antigen <10 ng/ml on watchful waiting, and 16% (95 CI% 13-19%) for men who did not receive curative-intent treatment or histological assessment. The study is limited by the historic nature of the observations over a period during which diagnostic procedures and treatments have evolved. CONCLUSIONS: GG 1 cancer can lead to disease-specific mortality in men with localized prostate cancer, and changing the nomenclature for all men may lead to undertreatment. PATIENT SUMMARY: Key opinion leaders have suggested that prostate cancers of Gleason grade group 1 (GG 1) should be renamed as noncancer to reduce overtreatment. The argument is that low-grade cancer does not metastasize. However, our nationwide population-based study showed that death from prostate cancer can occur in some men diagnosed with GG 1 disease. These men should be considered in discussions on changing the name for GG 1 prostate cancer.

Risk of prostate cancer and death after benign transurethral resection of the prostate-A 20-year population-based analysis.

BACKGROUND: The oncological risks after benign histology on a transurethral resection of the prostate (TURP) remain largely unknown. Here, the risk of prostate cancer incidence and mortality following a benign histological assessment of TURP is investigated in a population-based setting. METHODS: Between 1995 and 2016, 64,059 men in Denmark underwent TURP without prior biopsy of the prostate; 42,558 of these men had benign histology. The risks of prostate cancer, prostate cancer with a Gleason score ≥ 3 + 4, and prostate cancer-specific death were assessed with competing risks. Specific risks for pre-TURP prostate-specific antigen (PSA) levels at 10 and 15 years were visualized by locally estimated scatterplot smoothing. RESULTS: The median age at TURP was 72 years (interquartile range [IQR], 65-78 years), and the median follow-up was 15 years (IQR, 10-19 years). The 10-year risks of any prostate cancer and prostate cancer with a Gleason score ≥ 3 + 4 and the 15-year risk of prostate cancer death showed clear visual relations with increasing PSA. The 15-year cumulative incidence of prostate cancer-specific death after benign TURP was 1.4% (95% confidence interval [CI], 1.3%-1.6%) for all men and 0.8% (95% CI, 0.6%-1.1%) for men with PSA levels <10 ng/ml. The primary limitation was exclusion due to missing PSA data. CONCLUSIONS: Men with low PSA levels and a benign TURP can be reassured about their cancer risk and do not need to be monitored differently than any other men. Patients with high PSA levels can be considered for further follow-up with prostate magnetic resonance imaging. These findings add to the literature suggesting that normal histology from the prostate entails a low risk of death from the disease. LAY SUMMARY: There is little knowledge about the oncological risks after the surgical treatment of benign prostatic hyperplasia. This study shows a very low risk of adverse oncological outcomes in men with prostate-specific antigen (PSA) levels below 10 ng/ml at the time of transurethral resection of the prostate. Patients with higher PSA levels may need more extensive follow-up.

Active Surveillance for Localized Prostate Cancer: Nationwide Observational Study.

PURPOSE: The objective of this study was to investigate nationwide survival outcomes in men with localized prostate cancer managed on active surveillance. MATERIALS AND METHODS: A total of 936 men with localized prostate cancer were initiated on active surveillance in Denmark in 2002 to 2012. Kaplan-Meier estimated curative treatment-free, hormonal therapy-free, castration resistant prostate cancer-free and cause specific survival was calculated. RESULTS: Prostate cancer was classified as very low risk in 223 men, low risk in 436, intermediate risk in 259 (87% were at favorable intermediate risk) and high risk in 18. Median followup was 7.5 years (IQR 6.1-9.1). Kaplan-Meier estimated 10-year curative treatment-free survival was 62.8% (95% CI 59.1-66.3), 10-year hormonal therapy-free survival was 92.2% (95% CI 89.2-94.4), 10-year castration resistant prostate cancer-free survival was 97.2% (95% CI 95.3-98.4) and 10-year cause specific survival was 99.6% (95% CI 98.6-99.9). Compared to men with low risk prostate cancer, those with intermediate risk prostate cancer had higher curative treatment-free survival (69% vs 56%, p = 0.008), lower hormonal therapy-free survival (88% vs 95%, p = 0.005) and similar castration resistant prostate cancer-free survival (95% vs 99%, p = 0.17). CONCLUSIONS: In this nationwide cohort 10-year cause specific survival was similar to that in prospective active surveillance cohorts. Our study supports the use of active surveillance in men with localized prostate cancer, including men with favorable intermediate risk characteristics.

Risk of prostate cancer diagnosis and mortality in men with a benign initial transrectal ultrasound-guided biopsy set: a population-based study.

BACKGROUND: The risk of missing prostate cancer in the transrectal ultrasound-guided systematic biopsies of the prostate in men with suspected prostate cancer is a key problem in urological oncology. Repeat biopsy or MRI-guided biopsies have been suggested to increase sensitivity for diagnosis of prostate cancer, but the risk of disease-specific mortality in men who present with raised prostate-specific antigen (PSA) concentration and a benign initial biopsy result remains unknown. We investigated the risk of overall and prostate cancer-specific mortality in men with a benign initial biopsy set. METHODS: Data were extracted from the Danish Prostate Cancer Registry-a population-based registry including all men undergoing histopathological assessment of prostate tissue. All men who were referred for transrectal ultrasound-guided biopsy for assessment of suspected prostate cancer between Jan 1, 1995, and Dec 31, 2011, in Denmark were eligible for inclusion. Follow-up data were obtained on April 28, 2015. The primary endpoint was the cumulative incidence of prostate cancer-specific mortality, analysed in a competing risk setting, with death from other causes as the competing event. FINDINGS: Between Jan 1, 1995, and Dec 31, 2011, 64 430 men were referred for transrectal ultrasound-guided biopsy, of whom 63 454 were eligible for inclusion. Median follow-up was 5·9 years (IQR 3·8-8·5) and the total follow-up time, from the enrolment of the first patient on Jan 1, 1995, until the extraction of causes of death on April 28, 2015, was 20 years. 10 407 (30%) of 35 159 men with malignant initial biopsy sets died from prostate cancer, compared with 541 (2%) of 27 181 men with benign initial biopsy sets. Estimated overall 20-year mortality was 76·1% (95% CI 73·0-79·2). In all men referred for transrectal ultrasound-guided biopsy, the cumulative incidence of prostate cancer-specific mortality after 20 years was 25·6% (24·7-26·5) versus 50·5% (47·5-53·5) for mortality from other causes. In men with benign initial biopsy sets, the cumulative incidence of prostate cancer-specific mortality was 5·2% (3·9-6·5) versus 59·9% (55·2-64·6) for mortality from other causes. In men with PSA concentrations 10 µg/L or lower and benign initial biopsy sets (2779 men), the cumulative incidence of prostate cancer-specific mortality was 0·7% (0·2-1·3). Cumulative incidence of prostate cancer specific mortality in men with benign initial biopsy sets was 3·6% (95% CI 0·1-7·2) for men with a PSA higher than 10 ng/mL but 20 ng/mL or less (855 men) and 17·6% (12·7-22·4) and for men with a PSA higher than 20 ng/mL (454 men). INTERPRETATION: The first systematic transrectal ultrasound-guided biopsy set holds important prognostic information. The 20-year risk of prostate cancer-specific mortality in men with benign initial results is low. Our findings question whether men with low PSA concentration and a benign initial biopsy set should undergo further diagnostic assessment in view of the high risk of mortality from other causes. FUNDING: Capital Region of Denmark's Fund for Health Research, Danish Cancer Society, Danish Association for Cancer Research, and Krista and Viggo Petersen's Foundation.