Search

Background and Objective Changes in diagnostic work-up, histopathological assessment, and treatment of men with prostate cancer during the last 20 years have affected the prognosis. The objective was to investigate the risk of prostate cancer death in men with clinically localised prostate cancer treated with radical prostatectomy in Sweden in 2000–2010. Methods Population-based, nationwide, study on men with clinically localised prostate cancer treated with radical prostatectomy in the period 2000–2010. Cox regression analyses were used to assess differences in risk of prostate cancer death according to calendar period for diagnosis and stratified on risk category. Results The study included 19 330 men with a median follow-up of 12.4 years. Men diagnosed in 2007–2008 and 2009–2010 had a significantly lower risk of prostate cancer death compared to men diagnosed in 2000–2002. The reduced risk of prostate cancer death was restricted to men with intermediate-risk prostate cancer with no differences observed in men with low- or high-risk prostate cancer. Conclusion During the study period, the risk of prostate cancer death decreased in the total population of men with localised prostate cancer treated with radical prostatectomy. The decrease was restricted to men with intermediate-risk prostate cancer.

Background and Objective Changes in diagnostic work-up, histopathological assessment, and treatment of men with prostate cancer during the last 20 years have affected the prognosis. The objective was to investigate the risk of prostate cancer death in men with clinically localised prostate cancer treated with radical prostatectomy in Sweden in 2000–2010. Methods Population-based, nationwide, study on men with clinically localised prostate cancer treated with radical prostatectomy in the period 2000–2010. Cox regression analyses were used to assess differences in risk of prostate cancer death according to calendar period for diagnosis and stratified on risk category. Results The study included 19 330 men with a median follow-up of 12.4 years. Men diagnosed in 2007–2008 and 2009–2010 had a significantly lower risk of prostate cancer death compared to men diagnosed in 2000–2002. The reduced risk of prostate cancer death was restricted to men with intermediate-risk prostate cancer with no differences observed in men with low- or high-risk prostate cancer. Conclusion During the study period, the risk of prostate cancer death decreased in the total population of men with localised prostate cancer treated with radical prostatectomy. The decrease was restricted to men with intermediate-risk prostate cancer.

The objective was to investigate the proportion of men with metastatic prostate cancer in groups defined by T stage, Gleason Grade Group (GGG) and serum levels of prostate-specific antigen (PSA) and if PSA can be used to rule in metastatic prostate cancer when combined with T stage and GGG. We identified 102,076 men in Prostate Cancer data Base Sweden 4.0 who were diagnosed with prostate cancer in 2006-2016. Risk of metastases was assessed for PSA stratified on T stage and five-tiered GGG. For men who had not undergone bone imaging, we used multiple imputation to classify metastatic prostate cancer. Advanced T stage, high GGG and high PSA were related to bone metastases. For example: only 79/38 190 (0.2%) of men with T1-2 and GGG 1 had PSA above 500 ng/mL, and 29/79 (44%) of these men had metastases; whereas 1 154/7 018 (16%) of men with T3-4 and GGG 5 had PSA above 500 ng/ml and 1 088/1 154 (94%) of these men had metastases. However, no PSA cut-off could accurately identify the majority of men with metastatic prostate cancer (i.e. high sensitivity) while also correctly classifying most men without metastasis (i.e. high specificity). In conclusion, these results support the use of imaging to confirm bone metastases in men with advanced prostate cancer as no PSA level in combination with T stage and GGG could accurately rule in metastatic prostate cancer and thereby safely omit bone imaging.

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.

OBJECTIVE: The purpose of active surveillance (AS) is to reduce overtreatment of men with localized prostate cancer (PCa) without compromising survival. The objective of this study was to update a large Scandinavian single-center AS cohort. Furthermore, the use of curative treatment and subsequent risk of biochemical recurrence were investigated and compared in men with very low-risk, low-risk and intermediate-risk PCa in the cohort.MATERIALS AND METHODS: In total, 451 men were followed on AS and monitored with prostate-specific antigen (PSA) tests, digital rectal examinations and rebiopsies. Recommendation of curative treatment was based on protocolled and predefined risk of progression criteria. Biochemical recurrence was defined as PSA ≥0.2 ng/ml after radical prostatectomy and PSA nadir +2 ng/ml after radiotherapy.RESULTS: Altogether, 34% were defined with very low-risk PCa, 40% with low-risk PCa and 24% with intermediate-risk PCa. The median follow-up was 5.1 years. The estimated 5 year curatively intended treatment-free survival was 60.5% [95% confidence interval (CI) 54.8-66.2%], with no statistically significant difference between men with very low-risk, low-risk or intermediate-risk PCa. The 5 year biochemical recurrence-free survival was 92.3% (95% CI 87.4-97.2), again with no difference between men with very low-risk, low-risk and intermediate-risk PCa.CONCLUSION: AS for very low- to low-risk localized PCa is feasible and safe within the short to intermediate time frame. Men with intermediate-risk PCa had the same risk of undergoing curative treatment as men with low-risk PCa, without compromising biochemical recurrence-free survival.

Background: The Danish Cancer Registry holds information on all prostate cancers (PCa) cases, including diagnostic TNM. However, stratification according to contemporary risk classification is not possible because histopathological grading and prostate-specific antigen (PSA) level are not registered. The objective of the study was to report clinical characteristics and primary management of men diagnosed with PCa from a primary referral center in Denmark. Material and methods: Records on all men diagnosed with PCa at the Department of Urology, Frederiksberg Hospital, 1 January 2007 - 31 December 2013, were reviewed. Clinical characteristics and primary treatment were recorded. The National Comprehensive Cancer Network risk group classification was used. Results: A total of 1934 men with a median age of 69 years (interquartile range 65-75) were diagnosed with PCa in the study period resulting in an incidence rate (World Standard Population) of 84/100 000. Overall, 18% were classified as low-risk, 34% as intermediate-risk, 23% as high-risk, 8% as very high-risk and 17% had metastatic disease at diagnosis. Among men age <65 years 70% had low-or intermediate-risk disease, while this was the case for 58% of men aged 65-75 and 22% of men aged >75. Metastatic disease was found in 11% of men <65 years, 17% of men 65-75 years and 23% of men >75 years. In total 73% of men with low-risk PCa were managed on watchful waiting or active surveillance. Curatively intended treatment was performed in 56% of men with intermediate-risk and 61% of men with high-risk PCa, while hormonal therapy was used in 90% of men with very high-risk and 98% of men with metastatic PCa. Conclusion: In a population without systematic PSA testing we found a large proportion of patients presenting with advanced PCa at diagnosis. Elderly patients presented with more advanced disease. Curative treatment was primarily used in younger men with clinically localized PCa.

AIMS: The aims of the present study were to investigate referral patterns and the diagnosis of prostate cancer (PCa) before and after the Movember campaign was initiated in Denmark.METHODS: All men (n=2817) referred to the Department of Urology at Frederiksberg Hospital with suspicion of having PCa in the period 1 January 2007-31 January 2014 were identified. Based on the referral date, patients were categorised as pre-Movember (1 January 2007-31 January 2011) and Movember (1 February 2011-31 January 2014), respectively. Annual referral-rates/100.000 inhabitants were calculated and compared with rate-ratio (RR) tests.RESULTS: The median prostate-specific antigen (PSA) at referral dropped significantly from 9.8 ng/mL in 2007-2011 to 7.9 ng/mL in 2011-2014,p< 0.001. The incidence rate of men referred with suspicion of PCa increased from 134/100.000 in the pre-Movember period to 168/100.000 in the Movember period (RR 1.25 [95% CI 1.16-1.35]). In contrast to what we anticipated, there was no increase in referral in the months following the campaign. The incidence rates of men diagnosed with PCa and low-risk PCa were similar in the Movember period and the pre-Movember period (PCa: RR 1.08 [0.97-1.21]; low-risk PCa: RR 1.29 [0.98-1.73]).CONCLUSIONS: After the initiation of the Movember campaign a significant decline in the PSA level at referral and an increase in the number of patients referred under suspicion of PCa was observed; however, only minor differences in referral patterns and PCa diagnosis were detected. The results indicate that the Movember campaign had a limited immediate effect on referral, however, it may have contributed to an increased awareness of PCa.

BACKGROUND: The Danish Cancer Registry holds information on all prostate cancers (PCa) cases, including diagnostic TNM. However, stratification according to contemporary risk classification is not possible because histopathological grading and prostate-specific antigen (PSA) level are not registered. The objective of the study was to report clinical characteristics and primary management of men diagnosed with PCa from a primary referral center in Denmark.MATERIAL AND METHODS: Records on all men diagnosed with PCa at the Department of Urology, Frederiksberg Hospital, 1 January 2007 - 31 December 2013, were reviewed. Clinical characteristics and primary treatment were recorded. The National Comprehensive Cancer Network risk group classification was used.RESULTS: A total of 1934 men with a median age of 69 years (interquartile range 65-75) were diagnosed with PCa in the study period resulting in an incidence rate (World Standard Population) of 84/100 000. Overall, 18% were classified as low-risk, 34% as intermediate-risk, 23% as high-risk, 8% as very high-risk and 17% had metastatic disease at diagnosis. Among men age <65 years 70% had low- or intermediate-risk disease, while this was the case for 58% of men aged 65-75 and 22% of men aged >75. Metastatic disease was found in 11% of men <65 years, 17% of men 65-75 years and 23% of men >75 years. In total 73% of men with low-risk PCa were managed on watchful waiting or active surveillance. Curatively intended treatment was performed in 56% of men with intermediate-risk and 61% of men with high-risk PCa, while hormonal therapy was used in 90% of men with very high-risk and 98% of men with metastatic PCa.CONCLUSION: In a population without systematic PSA testing we found a large proportion of patients presenting with advanced PCa at diagnosis. Elderly patients presented with more advanced disease. Curative treatment was primarily used in younger men with clinically localized PCa.

OBJECTIVES: To investigate whether the International Society of Urological Pathology (ISUP) 2005 revision of the Gleason grading system has influenced the risk of biochemical recurrence (BCR) after radical prostatectomy (RP), as the new guideline implies that some prostate cancers previously graded as Gleason score 6 (3 + 3) are now considered as 7 (3 + 4).PATIENTS AND METHODS: A matched-pair analysis was conducted. In all, 215 patients with Gleason score 6 or 7 (3 + 4) prostate cancer on biopsy who underwent RP before 31 December 2005 (pre-ISUP group), were matched 1:1 by biopsy Gleason score, clinical tumour category, PSA level, and margin status to patients undergoing RP between 1 January 2008 and 31 December 2011 (post-ISUP group). Patients were followed until BCR defined as a PSA level of ≥0.2 ng/mL. Risk of BCR was analysed in a competing-risk model.RESULTS: The median follow-up was 9.5 years in the pre-ISUP group and 4.8 years in the post-ISUP group. The 5-year cumulative incidences of BCR were 34.0% and 13.9% in the pre-ISUP and post-ISUP groups, respectively (P < 0.001). The difference in cumulative incidence applied to both patients with Gleason score 6 (P < 0.001) and 7 (3 + 4) (P = 0.004). There was no difference in the 5-year cumulative incidence of BCR between patients with pre-ISUP Gleason score 6 and post-ISUP Gleason score 7 (3 + 4) (P = 0.34). In a multiple Cox-proportional hazard regression model, ISUP 2005 grading was a strong prognostic factor for BCR within 5 years of RP (hazard ratio 0.34; 95% confidence interval 0.22-0.54; P < 0.001).CONCLUSION: The revision of the Gleason grading system has reduced the risk of BCR after RP in patients with biopsy Gleason score 6 and 7 (3 + 4). This may have consequences when comparing outcomes across studies and historical periods and may affect future treatment recommendations.

BACKGROUND: The degree of antitumour activity of enzalutamide following disease progression on docetaxel and abiraterone remains controversial.OBJECTIVE: To examine the effect of enzalutamide in patients progressing following taxane-based chemotherapy and abiraterone.DESIGN, SETTING, AND PARTICIPANTS: Metastatic castration-resistant prostate cancer patients entering one of four European compassionate use programmes of enzalutamide.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was overall survival (OS). Secondary end points were association between OS and posttreatment prostate-specific antigen (PSA) kinetics, patient characteristics, and progression-free survival, respectively. Kaplan-Meier survival analysis and Cox proportional hazard analysis were performed.RESULTS AND LIMITATIONS: We identified 137 patients who prior to enzalutamide had progressed following a median of eight cycles of docetaxel and seven courses of abiraterone. The median time on enzalutamide was 3.2 mo; median OS from the time patients started enzalutamide was 8.3 mo (95% confidence interval, 6.8-9.8). Only 45 (38%) and 22 (18%) patients had PSA declines (unconfirmed) >30% and 50%, respectively. Patients who had more than 30% or 50% falls in PSA had improved survival compared with patients who had no such PSA fall (11.4 mo vs 7.1 mo; p=0.001 and 12.6 vs 7.4 mo; p=0.007, respectively). Poor performance status and low haemoglobin was negatively associated with OS.CONCLUSIONS: Median OS on enzalutamide following disease progression on taxane-based chemotherapy and abiraterone was modest, but patients who experience a PSA decline >30% or 50%, respectively, with enzalutamide in this setting had longer survival.PATIENT SUMMARY: Enzalutamide produces modest prostate-specific antigen (PSA) responses in patients progressing following chemotherapy and abiraterone. Despite a modest PSA response, survival may still be improved.

OBJECTIVE: Evidence supports active surveillance (AS) as a means to reduce overtreatment of low-risk prostate cancer (PCa). The consequences of close and long-standing follow-up with regard to outpatient visits, tests and repeated biopsies are widely unknown. This study investigated the trajectory and costs of AS in patients with localized PCa.MATERIALS AND METHODS: In total, 317 PCa patients were followed in a prospective, single-arm AS cohort. The primary outcomes were number of patient contacts, prostate-specific antigen (PSA) tests, biopsies, hospital admissions due to biopsy complications and patients eventually undergoing curative treatment. The secondary outcome was cost.RESULTS: The 5 year cumulative incidence of discontinued AS in a competing-risk model was 40%. During the first 5 years of AS patients underwent a median of two biopsy sets, and patients were seen in an outpatient clinic including PSA testing three to four times annually. In total, 38 of the 406 biopsy sessions led to hospital admission and 87 of the 317 patients required treatment for bladder outlet obstruction (BOO). With a median of 3.7 years' follow-up, the total cost of AS was euro (€) 1,240,286. Assuming all patients had otherwise undergone primary radical prostatectomy, the cost difference favoured AS with a net benefit of €662,661 (35% reduction).CONCLUSIONS: AS entails a close clinical follow-up with a considerable risk of rebiopsy complication, treatment of BOO and subsequent delayed definitive therapy. This risk should be weighed against a potential economic benefit and reduction in the risk of overtreatment compared to immediate radical treatment.

Background The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. Methods A randomised, double-blind, parallel-group trial comparing bicalutamide 150 mg once daily with placebo in addition to standard care in patients with hormone-naïve, non-metastatic PCa. Kaplan–Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). Findings A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised to receive bicalutamide in addition to their standard care and 611 to receive placebo. Median follow-up was 14.6 years. Overall, 866 (71.1%) patients died, 428 (70.5%) in the bicalutamide arm and 438 (71.7%) in the placebo arm, p = 0.87. Bicalutamide significantly improved OS in patient with locally advanced disease (hazard ratios (HR) = 0.77 (95% confidence interval (CI): 0.63–0.94, p = 0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised disease (HR = 1.19 (95% CI: 1.00–1.43), p = 0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28 ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting as their standard of care (n = 991) OS depended on age, World Health Organisation (WHO) grade, baseline PSA, clinical stage and randomised treatment., BACKGROUND: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate.METHODS: A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non-metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death).FINDINGS: A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised to receive bicalutamide in addition to their standard care and 611 to receive placebo. Median follow-up was 14.6years. Overall, 866 (71.1%) patients died, 428 (70.5%) in the bicalutamide arm and 438 (71.7%) in the placebo arm, p=0.87. Bicalutamide significantly improved OS in patient with locally advanced disease (hazard ratios (HR)=0.77 (95% confidence interval (CI): 0.63-0.94, p=0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised disease (HR=1.19 (95% CI: 1.00-1.43), p=0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting as their standard of care (n=991) OS depended on age, World Health Organisation (WHO) grade, baseline PSA, clinical stage and randomised treatment.INTERPRETATION: Throughout the 14.6year follow-up period the addition of early bicalutamide to standard of care resulted in a significant OS benefit in patients with locally advanced PCa. In contrast, patients with localised PCa and low PSA derived no survival benefit from early bicalutamide. The optimal ti

BACKGROUND: Biomarkers predicting response to primary androgen deprivation therapy (ADT) and risk of castration-resistant prostate cancer (CRPC) is lacking. We aimed to analyse the predictive value of ERG expression for development of CRPC.METHODS: In total, 194 patients with advanced and/or metastatic prostate cancer (PCa) treated with first-line castration-based ADT were included. ERG protein expression was analysed in diagnostic specimens using immunohistochemistry (anti-ERG, EPR3864). Time to CRPC was compared between ERG subgroups using multiple cause-specific Cox regression stratified on ERG-status. Risk reclassification and time-dependent area under the ROC curves were used to assess the discriminative ability of ERG-status. Time to PSA-nadir, proportion achieving PSA-nadir ≤0.2 ng/ml, and risk of PCa-specific death were secondary endpoints.RESULTS: Median follow-up was 6.8 years (IQR: 4.9-7.3). In total, 105 patients (54.1%) were ERG-positive and 89 (45.9%) were ERG-negative. No difference in risk of CRPC was observed between ERG subgroups (P = 0.51). Median time to CRPC was 3.9 years (95%CI: 3.2-5.1) and 4.5 years (95%CI: 2.3-not reached) in the ERG-positive and ERG-negative group, respectively. Compared to a model omitting ERG-status, the ERG-stratified model showed comparable AUC values 1 year (77.6% vs. 78.0%, P = 0.82), 2 years (71.7% vs. 71.8%, P = 0.85), 5 years (68.5% vs. 69.9%, P = 0.32), and 8 years (67.9% vs. 71.4%, P = 0.21) from ADT initiation. No differences in secondary endpoints were observed.CONCLUSIONS: ERG expression was not associated with risk of CRPC suggesting that ERG is not a candidate biomarker for predicting response to primary ADT in patients diagnosed with advanced and/or metastatic PCa.

BACKGROUND: Germ-cell cancer (GCC) patients aged ≥40 years have a two-fold higher GCC-specific mortality. It has been hypothesized that reduced treatment intensity combined with increased treatment related toxicity could be the explanation. The objective was to analyze chemotherapy intensity, treatment related toxicity and survival in patients aged ≥40 years treated with standard chemotherapy for GCC compared with a younger control group that received similar treatment during the same period.METHODS: From 1984 to 2011, 135 patients aged ≥40 years with disseminated GCC treated with bleomycin, etoposide and cisplatin (BEP). A control-group of 135 patients aged 18-35 years was randomly selected matched on year of BEP treatment. Cumulated doses of BEP as well as bone marrow toxicity, renal- and lung functions were recorded before, during and after termination of treatment. All patients were followed until death or October 1, 2011.RESULTS: The cumulated doses of BEP were comparable between the two groups, however, more patients aged ≥40 years were reduced in bleomycin doses based on a decrease in carbon monoxide diffusion capacity corrected for haemoglobin (P = 0.03). No differences between the two groups were found regarding bone marrow toxicity or mean percentage changes in lung- or renal function. Patients aged ≥40 year had increased cancer specific mortality, HR = 4.8 (P = 0.005). In particular patients with disease progression after first line chemotherapy had increased mortality (P = 0.015). Moreover, the 5-year overall survival for patients aged ≥40 years was 82.5% compared to the expected 5-year survival of the background population of 96.3% (P <0.001).CONCLUSIONS: Treatment related toxicity could not explain the increased cancer specific mortality in patients aged ≥40 years compared to a younger control-group, and while there were no differences in the administrated doses of cisplatin/etoposide, a decreased number of bleomycin doses we

Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection for the AS strategy and how they should be managed within the program. However, uncertainties persists concerning optimal patient selection and reliable progression criteria, as well as the long-term safety of AS.