National Prostate Cancer Register Research Articles

Natural History of Nonmetastatic Prostate Cancer Managed With Watchful Waiting

It is uncertain to what extent watchful waiting (WW) in men with nonmetastatic prostate cancer (PCa) and a life expectancy of less than 10 years is associated with adverse consequences. To report transitions to androgen deprivation therapy (ADT), castration-resistant prostate cancer (CRPC), death from PCa, or death from other causes in men treated with a WW strategy. This nationwide, population-based cohort study included men with nonmetastatic PCa diagnosed since 2007 and registered in the National Prostate Cancer Register of Sweden with WW as the primary treatment strategy and with life expectancy less than 10 years. Life expectancy was calculated based on age, the Charlson Comorbidity Index (CCI), and a drug comorbidity index. Observed state transition models complemented observed data to extend follow-up to more than 20 years. Analyses were performed between 2022 and 2023. Nonmetastatic PCa. Transitions to ADT, CRPC, death from PCa, and death from other causes were measured using state transition modeling. The sample included 5234 men (median [IQR] age at diagnosis, 81 [79-84] years). After 5 years, 954 men with low-risk PCa (66.2%) and 740 with high-risk PCa (36.1%) were still alive and not receiving ADT. At 10 years, the corresponding proportions were 25.5% (n = 367) and 10.4% (n = 213), respectively. After 10 years, 59 men with low-risk PCa (4.1%) and 221 with high-risk PCa (10.8%) had transitioned to CRPC. Ten years after diagnosis, 1330 deaths in the low-risk group (92.3%) and 1724 in the high-risk group (84.1%) were from causes other than PCa. These findings suggest that the WW management strategy is appropriate for minimizing adverse consequences of PCa in men with a baseline life expectancy of less than 10 years.

Risk of prostate cancer death in men diagnosed with prostate cancer at cystoprostat-ectomy. A nationwide population-based study.

One out of three men who undergo cystoprostatectomy for bladder cancer is diagnosed with incidental prostate cancer (PCa) at histopathological examination. Many of these men are PSA tested as part of their follow-up, but it is unclear if this is needed. The aim of this study was to assess the risk of PCa death in these men and the need of PSA-testing during follow-up. Between 2002 and 2020, 1,554 men were diagnosed with PCa after cystoprostatectomy performed for non-metastatic bladder cancer and registered in the National Prostate Cancer Register (NPCR) of Sweden. We assessed their risk of death from PCa, bladder cancer and other causes up to 15 years after diagnosis by use of data in The Cause of Death Register. The use of androgen deprivation therapy (ADT) as a proxy for PCa progression was assessed by fillings in The Prescribed Drug Register. Fifteen years after diagnosis, cumulative incidence of death from PCa was 2.6% (95% CI 2.3%-2.9%), from bladder cancer 32% (95% CI: 30%-34%) and from other causes 40% (95% CI: 36%-44%). Only 35% of men with PCa recorded as primary cause of death in The Cause of Death Register had started ADT before date of death, indicating sticky-diagnosis bias with inflated risk of PCa death. For a large majority of men diagnosed with incidental PCa at cystoprostatectomy performed for bladder cancer, the risk of PCa death is very small so there is no rationale for PSA testing during follow-up.

Triggers for transition from active surveillance to radical treatment of prostate cancer 2008-2020 - a case-control study.

To examine associations between objective signs of progression (triggers) and transition from active surveillance (AS) to radical treatment for prostate cancer (PC). This case-control study included men with low- or favourable intermediate-risk PC in the region of Halland, with data from The National Prostate Cancer Register (NPCR), Sweden, starting AS between 2008 and 2020. Cases were men who transitioned to radical treatment. For each case, 10 controls who remained in AS were selected without further matching. Triggers for transition to treatment were histopathological progression, magnetic resonance imaging (MRI) progression and increases in prostate-specific antigen (PSA) levels. We compared the probabilities for triggers between cases and controls, in 2008-2014 and 2015-2020, using logistic regression. Amongst 846 men, we identified 98 cases in 2008-2014 and 172 cases in 2015-2020. Histopathological progression was associated with transition, most strongly in the later period (2008-2014: odds ratios [OR] 6.88, 95% confidence interval [CI] 3.69-12.80; and 2015-2020: OR 75.29, 95% CI 39.60-143.17). MRI progression was associated with transition in 2015-2020 (OR 6.38, 95% CI 2.70-15.06), whereas an increase in PSA was weakly associated with transition in the early period. The absence of triggers was associated with no transition (2008-2014: OR 0.24, 95% CI 0.15-0.40, and 2015-2020: OR 0.09, 95% CI 0.06-0.14). The probability of no trigger was 27% in cases 2015-2020. The increase in association between histopathological trigger and transition to treatment indicates increased quality of AS. Still, amongst men treated from 2015 to 2020, 27% transitioned without any trigger.

Uptake of doublet therapy for de novo metastatic castration sensitive prostate cancer: a population-based drug utilisation study in Sweden.

Randomised controlled trials have demonstrated prolonged survival with new upfront treatments in addition to standard androgen deprivation therapy (ADT) in men with de novo metastatic castration-sensitive prostate cancer. We describe patient characteristics, time trends and regional differences in uptake of these new treatment strategies in clinical practice. This descriptive study consisted of men registered in the National Prostate Cancer Register of Sweden from 1 January 2018 to 31 March 2022 with de novo metastatic castration-sensitive prostate cancer defined by the presence of metastases on imaging at the time of diagnosis. Life expectancy was calculated based on age, Charlson Comorbidity Index and a Drug Comorbidity Index. Within 6 months from diagnosis, 57% (1,677/2,959) of men with de novo metastatic castration-sensitive prostate cancer and more than 3 years of life expectancy had received docetaxel, abiraterone, enzalutamide, apalutamide and/or radiotherapy. Over time, there was a 2-fold increase in uptake of any added treatment, mainly driven by a 6-fold increase in use of abiraterone, enzalutamide or apalutamide, with little change in use of other treatments. Slightly more than half of men diagnosed with de novo metastatic castration-sensitive prostate cancer and a life expectancy of at least 3 years received additions to standard ADT as recommended bynational guidelines in 2019-2022 in Sweden. There was a 2-fold increase in use of these treatments during the study period; however, efforts to further increase adherence to guidelines are warranted.

Variations in the Uptake of Active Surveillance for Prostate Cancer and Its Impact on Outcomes

BackgroundRegional differences in active surveillance (AS) uptake for prostate cancer (PC) illustrate an inequality in treatment strategies. ObjectiveTo examine the association between regional differences in AS uptake and transition to radical treatment, start of androgen deprivation therapy (ADT), watchful waiting, or death. Design, setting, and participantsA Swedish population-based cohort study was conducted including men in the National Prostate Cancer Register in Sweden with low-risk or favorable intermediate-risk PC, starting AS from January 1, 2007 and continuing till December 31, 2019. InterventionRegional tradition of low, intermediate, or high proportions of immediate radical treatment. Outcomes measurements and statistical analysisProbabilities of transition from AS to radical treatment, start of ADT, watchful waiting, or death from other causes were assessed. Results and limitationsWe included 13 679 men. The median age was 66 yr, median PSA 5.1 ng/ml, and median follow-up 5.7 yr. Men from regions with a high AS uptake had a lower probability of transition to radical treatment (36%) than men from regions with a low AS uptake (40%; absolute difference 4.1%; 95% confidence interval [CI] 1.0–7.2), but not a higher probability of AS failure defined as the start of ADT (absolute difference 0.4%; 95% CI –0.7 to 1.4). There were no statistically significant differences in the probability of transition to watchful waiting or death from other causes. Limitations include uncertainty in the estimation of remaining lifetime and transition to watchful waiting. ConclusionsA regional tradition of a high AS uptake is associated with a lower probability of transition to radical treatment, but not with AS failure. A low AS uptake suggests overtreatment. Patient summaryThere are considerable regional differences in active surveillance (AS) uptake for prostate cancer. This study compared the outcomes of AS in different regions and found no association between AS uptake and failure of AS; it suggests that a low AS uptake indicates overtreatment.

PD27-09 PATIENT REPORTED OUTCOMES AFTER RADICAL PROSTATECTOMY OR RADIOTHERAPY FOR PROSTATE CANCER, A REGISTER-BASED NATIONWIDE STUDY

You have accessJournal of UrologyCME1 Apr 2023PD27-09 PATIENT REPORTED OUTCOMES AFTER RADICAL PROSTATECTOMY OR RADIOTHERAPY FOR PROSTATE CANCER, A REGISTER-BASED NATIONWIDE STUDY Oskar Bergengren, Christian Corsini, Stefan Carlsson, Ingela Franck-Lissbrant, Hans Garmo, Marie Hjelm-Eriksson, Per Fransson, Jon Kindblom, David Robinson, Marcus Westerberg, Pär Stattin, and Sigrid Carlsson Oskar BergengrenOskar Bergengren More articles by this author , Christian CorsiniChristian Corsini More articles by this author , Stefan CarlssonStefan Carlsson More articles by this author , Ingela Franck-LissbrantIngela Franck-Lissbrant More articles by this author , Hans GarmoHans Garmo More articles by this author , Marie Hjelm-ErikssonMarie Hjelm-Eriksson More articles by this author , Per FranssonPer Fransson More articles by this author , Jon KindblomJon Kindblom More articles by this author , David RobinsonDavid Robinson More articles by this author , Marcus WesterbergMarcus Westerberg More articles by this author , Pär StattinPär Stattin More articles by this author , and Sigrid CarlssonSigrid Carlsson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003305.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The two main alternatives for curative treatment of prostate cancer (PCa) are robot assisted radical prostatectomy (RARP) and radiotherapy (RT). We assessed outcomes after RARP and RT by use of Patient Reported Outcomes Measures (PROM) in a large, contemporary population. METHODS: The National Prostate Cancer Register of Sweden (NPCR) includes information on almost all Swedish men with PCa. The PCa Data Base Sweden (PCBaSe) links data to multiple national population-based registries. PROM are distributed to all men scheduled for curative treatment. 12 month PROM were used to evaluate the outcomes erectile dysfunction, urinary symptoms, bowel dysfunction, and quality of life (QoL). Data for all men who completed 12 month PROM in PCBaSe 5.0 aged <75 years, with clinical T1c-T3 or Tx, any Gleason score, preoperative PSA levels <l00 ng/mL, no metastases (N0, Nx. M0 or Mx) who underwent RARP or RT between 1 January 2018 and 31 December 2020 were analyzed (n=4298). Comorbidities were assessed by Charlson Comorbidity Index and a Drug Comorbidity Index. Adjusted odds ratios (OR) for each outcome comparing RT vs RARP (reference) were obtained using logistic regression, adjusting for confounders at date of treatment (age, comorbidities, educational level, civil status, PSA, prostate volume, biopsies with cancer, cT-stage and Gleason score). RESULTS: 2557 men underwent RARP and 1741 men received RT. On average, men who had undergone RT were 4 years older and had more comorbidities. The prevalence of erectile dysfunction was 80% among men who underwent RARP and 82% among RT. 13% of the men were incontinent one year after RARP while only 5% reported incontinence after RT. 17% of men treated with RT and 18% with RARP reported high urinary bother. 34% of men who underwent RT reported urgency to defecate compared to 14% of men treated with RARP. High QoL was reported by 85% of men who underwent RARP and 79% who underwent RT. RT was associated with lower risk of erectile dysfunction (OR 0.57, 95% CI 0.48-0.67), lower risk of urine incontinence (OR 0.24, 95% CI 0.19-0.32), lower urinary bother (OR 0.74, 95% CI 0.61-0.89) but higher risk of bowel related symptoms (OR 2.84 95%, CI: 2.40-3.37). RARP was associated with higher QoL (OR 1.33, 95% CI: 1.11-1.60). CONCLUSIONS: Results from this large, contemporary, and unselected population confirms previous reports on common side-effects after curative treatment for PCa. However, QoL is high regardless of treatment suggesting that factors other than side-effects are the main drivers of QoL. Source of Funding: National Institutes of Health/National Cancer Institute (K22 CA234400) to Dr. Carlsson and Hillevi Fries Research Foudation, Johanna Hagstrand and Sigfrid Linnérs Research Foundation, Nyströms America Scholarship, and the Swedish Society of Medicine to Dr. Bergengren © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e745 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Oskar Bergengren More articles by this author Christian Corsini More articles by this author Stefan Carlsson More articles by this author Ingela Franck-Lissbrant More articles by this author Hans Garmo More articles by this author Marie Hjelm-Eriksson More articles by this author Per Fransson More articles by this author Jon Kindblom More articles by this author David Robinson More articles by this author Marcus Westerberg More articles by this author Pär Stattin More articles by this author Sigrid Carlsson More articles by this author Expand All Advertisement PDF downloadLoading ...

Hyaluronic acid spacer in prostate cancer radiotherapy: dosimetric effects, spacer stability and long-term toxicity and PRO in a phase II study

BackgroundPerirectal spacers may be beneficial to reduce rectal side effects from radiotherapy (RT). Here, we present the impact of a hyaluronic acid (HA) perirectal spacer on rectal dose as well as spacer stability, long-term gastrointestinal (GI) and genitourinary (GU) toxicity and patient-reported outcome (PRO).MethodsIn this phase II study 81 patients with low- and intermediate-risk prostate cancer received transrectal injections with HA before external beam RT (78 Gy in 39 fractions). The HA spacer was evaluated with MRI four times; before (MR0) and after HA-injection (MR1), at the middle (MR2) and at the end (MR3) of RT. GI and GU toxicity was assessed by physician for up to five years according to the RTOG scale. PROs were collected using the Swedish National Prostate Cancer Registry and Prostate cancer symptom scale questionnaires.ResultsThere was a significant reduction in rectal V70% (54.6 Gy) and V90% (70.2 Gy) between MR0 and MR1, as well as between MR0 to MR2 and MR3. From MR1 to MR2/MR3, HA thickness decreased with 28%/32% and CTV-rectum space with 19%/17% in the middle level. The cumulative late grade ≥ 2 GI toxicity at 5 years was 5% and the proportion of PRO moderate or severe overall bowel problems at 5 years follow-up was 12%. Cumulative late grade ≥ 2 GU toxicity at 5 years was 12% and moderate or severe overall urinary problems at 5 years were 10%.ConclusionWe show that the HA spacer reduced rectal dose and long-term toxicity.

Hyaluronic Acid Spacer in Prostate Cancer Radiotherapy: Dosimetric Effects, Spacer Stability and Long-Term GI Toxicity and PRO in a Phase II-Study

<h3>Purpose/Objective(s)</h3> Rectal side effects are common after radiotherapy (RT) to the prostate. To reduce side effects, perirectal spacers to separate the prostate from the rectum, thereby reducing the rectal dose, may be beneficial. This study presents the impact of a hyaluronic acid (HA) perirectal spacer on the rectal dose, MRI evaluation of spacer thickness during RT and a five-year follow-up of patient-reported outcome (PRO) and gastrointestinal (GI) toxicity. <h3>Materials/Methods</h3> 81 patients (<75 years) with low- (T1c-T2 and Gleason ≤ 6 and PSA < 10) and intermediate-risk prostate cancer (PC) (T1c-T3a with 1 or 2 of the risk factors T2c-T3a or Gleason ≥ 7 or PSA ≥ 10) received transrectal injections with HA (Macrolane VRF 30, Q-Med/Galderma, Uppsala, Sweden) as a perirectal spacer in this phase II-study between 2010-2016. External beam RT, 78 Gy in 39 fractions, were given with 3DCRT or IMRT using fiducial markers as image guidance. MRI was performed before (MR0) and after HA injection (MR1), at the middle (MR2) and at the end of RT (MR3). GI toxicity was assessed up to five years according to the RTOG scale. PRO GI side effects were collected using The Swedish national prostate cancer registry (NPCR) and PCSS questionnaires. <h3>Results</h3> HA thickness was measured at the prostate base, middle and apex for 52 of 81 patients. Exclusion due to failed HA-injections (6), missing MRT or RT data (17), larger PTV margins (5) and other treatment (1). HA thickness and CTV-Rectum spaces in apex- and middle- position was decreasing from MR1 to MR2/MR3. No significant differences were found between MR2 and MR3. Overall, HA thickness in the middle position had the strongest significant correlation (Spearman's rho ρ= 0.70) to CTV-Rectum spacing. There was a significant decrease in the relative rectum volume that received 70.2 Gy (V90%) from MR0 (8.6 ±5.7 %) to MR1 (2.7± 4.1 %). There was a significant increase from MR1 to MR2 (6.0±9.0%) and no significant difference between MR2 and MR3 (5.7±7.9 %) in rectum V90%. All with significance p<0.05. At the end of RT 17 patients (25.8%) experienced grade 1 GI toxicity, and four patients (6.1%) grade 2. At six months the proportion of grade 2 and 3 GI toxicity was 3.2%, and 1.6%. After 18 months no grade ≥ 2 GI toxicity was observed. The estimated cumulative late grade ≥ 2 GI toxicity rate at 5 years was 4.8 %. PRO moderate or severe overall bowel problems at start RT, end of RT and 5 years were 0%, 17.6% and 12.2% with a mean score of 14.6 (scale 0–100; higher value refers to more symptoms/worse function) at 5 years. <h3>Conclusion</h3> After HA-spacer, the relative rectum volumes receiving 70.2 Gy (V90%) were significantly lower. V90% increased significantly from MR1 to MR2/MR3, but still a significant reduction from MR0. The 5-year cumulative risk of late GI toxicity grade >1 was low whereas 12 % reported moderate/severe GI-bothers in the PRO at 5 years.

Surgeon volume and patient-reported urinary incontinence after radical prostatectomy. Population-based register study in Sweden

Objective To investigate the association between surgeon volume and urinary incontinence after radical prostatectomy. Methods A total of 8326 men in The National Prostate Cancer Register of Sweden (NPCR) underwent robot-assisted radical prostatectomy (RARP) between 2017 and 2019 of whom 56% (4668/8 326) had responded to a questionnaire one year after RARP. The questionnaire included the question: ‘How much urine leakage do you experience?’ with the response alternatives ‘Not at all’, ‘A little’, defined as continence and ‘Moderately’, ‘Much/Very much’ as incontinence. Association between incontinence and mean number of RARPs/year/surgeon was analysed with multivariable logistic regression including age, Charlson Comorbidity Index (CCI), PSA, prostate volume, number of biopsy cores with cancer, cT stage, Gleason score, lymph node dissection, nerve sparing intent and response rate to the questionnaire. Results 14% (659/4 668) of the men were incontinent one year after RARP. There was no statistically significant association between surgeon volume and incontinence. Older age (>75 years vs. < 65 years, OR 2.29 [95% CI 1.48–3.53]), higher CCI (CCI 2+ vs. CCI 0, OR 1.37 [95% CI 1.04–1.80]) and no nerve sparing intent (no vs. yes OR 1.53 [95% CI 1.26–1.85]) increased risk of incontinence. There were large differences in the proportion of incontinent men between surgeons with similar annual volumes, which remained after adjustment. Conclusions The lack of association between surgeon volume and incontinence and the wide range in outcome between surgeons with similar volumes underline the importance of individual feedback to surgeons on functional results.

Changes in Characteristics of Men with Lethal Prostate Cancer During the Past 25 Years: Description of Population-based Deaths

BackgroundAttempts to reduce prostate cancer (PC) mortality require an understanding of temporal changes in the characteristics of men with lethal PC. ObjectiveTo describe the diagnostic characteristics of and time trends for a nationwide population-based cohort of Swedish men who died from PC between 1992 and 2016. Design, setting, and participantsMen with PC as the underlying cause of death from 1992 to 2016 according to the Swedish Cause of Death Register were included in the study. Characteristics at diagnosis were collected via links to other nationwide registries using personal identity numbers. Outcome measurements and statistical analysisData on disease duration, age at death, and risk category were analyzed. Missing data for risk categories for men with an early date of PC diagnosis were imputed according to the method of chained equations. Results and limitationsBetween 1992 and 2016, age-standardized PC mortality decreased by 25%. Median PC disease duration increased from 3.3 yr (interquartile range [IQR] 1.6–6.3) to 5.9 yr (IQR 2.5–10.3) and the median age at death from PC increased from 78.9 yr (IQR 73.3–84.2) to 82.2 yr (IQR 75.2–87.5). The proportion of men with localized disease at diagnosis who died from PC increased from 34% to 48%, while the rate of distant metastases at diagnosis decreased from 56% to 42%. The rate of distant metastases at diagnosis was highest among the youngest men. Treatment trajectories could not be described owing to the large proportion of missing data before the start of registration in the National Prostate Cancer Registry. ConclusionAge-standardized PC mortality has decreased substantially since 1992. However, there is still a high proportion of men who die from PC who had localized disease at diagnosis, which indicates that more attention is needed to identify the underlying causes to prevent disease progression. Since the proportion of men with distant metastases at diagnosis remains high, early detection of lethal tumors is essential to further reduce PC mortality. Patient summaryWe investigated the characteristics of men who died from prostate cancer in Sweden between 1992 and 2016. We found that men with lethal prostate cancer live longer and are older when they die today in comparison to men who died at the beginning of the study period. However, the proportion of men with distant metastases at diagnosis remains high, which is why early detection of lethal tumors is essential to reduce mortality.

Time to castration-resistant prostate cancer and prostate cancer death according to PSA response in men with non-metastatic prostate cancer treated with gonadotropin releasing hormone agonists

Objectives: To predict castration-resistant prostate cancer (CRPC) and prostate cancer (Pca) death by use of clinical variables at Pca diagnosis and PSA levels after start of gonadotropin-releasing hormone agonists (GnRH) in men with non-metastatic castration sensitive prostate cancer (nmCSPC). Materials and Methods: PSA values for 1603 men with nmCSPC in the National Prostate Cancer Register of Sweden who received GnRH as primary treatment were retrieved from Uppsala-Örebro PSA Cohort and Stockholm PSA and Biopsy Register. All men had measured PSA before (pre-GnRH PSA) and 3–6 months after (post-GnRH PSA) date of start of GnRH. Unadjusted and adjusted Cox models were used to predict CRPC by PSA levels. PSA levels and ISUP grade were used to construct a risk score to stratify men by tertiles according to risk of CRPC and Pca death. Results: 788 (49%) men reached CRPC and 456 (28%) died of Pca during follow-up. Post-GnRH PSA predicted CRPC regardless of pre-GnRH PSA. CRPC risk increased with higher post-GnRH PSA, HR 4.7 (95% CI: 3.4–6.7) for PSA > 16 ng/mL vs 0–0.25 ng/mL and with ISUP grade, HR 3.7 (95%: 2.5–5.4) for ISUP 5 vs ISUP 1. Risk of Pca death in men above top vs bellow bottom tertile of post-GnRH PSA and ISUP grade was HR 4.1 (95% CI: 3.0–5.5). Conclusion: A risk score based on post-GnRH PSA and ISUP grade could be used for early identification of a target group for future clinical trials on additional therapy to GnRH.

PD03-01 MRI AS FIRST INVESTIGATION IN MEN WITH ELEVATED PSA. POPULATION-BASED COHORT STUDY

You have accessJournal of UrologyCME1 May 2022PD03-01 MRI AS FIRST INVESTIGATION IN MEN WITH ELEVATED PSA. POPULATION-BASED COHORT STUDY David Robinsson, Hans Garmo, Delshad Nasrollah, Tiago Bonde Miranda, and Pär Stattin David RobinssonDavid Robinsson More articles by this author , Hans GarmoHans Garmo More articles by this author , Delshad NasrollahDelshad Nasrollah More articles by this author , Tiago Bonde MirandaTiago Bonde Miranda More articles by this author , and Pär StattinPär Stattin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002518.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In randomized controlled trials of men with elevated PSA, MRI before prostate biopsy resulted in fewer insignificant cancers defined as Gleason Score ≤6 while the detection of significant cancers defined as Gleason Score ≥7 increased. The aim of this study was assessed if these results from RCT’s can be reproduced in clinical practice including all men with elevated PSA in a region. METHODS: Data on all PSA values between 2010-2020 and all prostate biopsies performed in 2005-2020 and use of MRI were collected for all men in the region of Jönköping. These data were linked to The National Prostate Cancer Register. Before 1 January 2020 only select cases underwent MRI whereas after that, there was unlimited access to MRI in this region. Results for all men who underwent biopsy 2016-2019 when prior use of MRI was low was compared to all men who underwent biopsy in 2020 when usage of MRI was high. Outcome was number of men who underwent prostate biopsy, benign or malignant pathology report, and distribution of Gleason score. RESULTS: First investigation in men with elevated PSA was 66 MRIs in 2016 and 681 MRIs in 2020. Out of these 681 MRIs, 317 were performed on men who had undergone at least one previous biopsy set with negative result before MRI, their risk of cancer was 9 % on biopsy after MRI. In contrast, 51 % of biopsy naive men who underwent an MRI had cancer on subsequent biopsy. The number of men who performed a biopsy as first investigation was 630 in 2016 and 190 in 2020. The median PSA was 8.5 ng/mL in 2016-2019 vs 8.0 in 2020. In 2020, 499 biopsies were performed vs an average of 598 in 2016-2019. The number of biopsies without cancer was 167 for 2020 vs an average of 216 in 2016-2019. There was no difference in the number of significant tumors between 2020 and 2016-2019, 267 in 2020 vs an average of 256 in 2016-2019. In contrast, there was a decrease from an average of 126 insignificant cancers per year in 2016-2019 vs. 65 in 2020, (figure). CONCLUSIONS: When MRI became available without any limitations in our region, the number of prostate biopsy sessions decreased by 20%, the numbers of significant tumors remained the same, and the number of insignificant cancers decreased by 48%. Source of Funding: Stiftelsen fonden klinisk cancerforskning i Jönköping © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e41 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Robinsson More articles by this author Hans Garmo More articles by this author Delshad Nasrollah More articles by this author Tiago Bonde Miranda More articles by this author Pär Stattin More articles by this author Expand All Advertisement PDF DownloadLoading ...

MP27-01 TIME ON TREATMENT WITH ABIRATERONE IN MEN WITH DE NOVO METASTATIC CASTRATION SENSITIVE PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022MP27-01 TIME ON TREATMENT WITH ABIRATERONE IN MEN WITH DE NOVO METASTATIC CASTRATION SENSITIVE PROSTATE CANCER Pär Stattin, Hans Garmo, Camilla Thellenberg-Karlsson, Giuseppe Fallara, Johan Styrke, Ingela Franck Lissbrant, and Rolf Gedeborg Pär StattinPär Stattin More articles by this author , Hans GarmoHans Garmo More articles by this author , Camilla Thellenberg-KarlssonCamilla Thellenberg-Karlsson More articles by this author , Giuseppe FallaraGiuseppe Fallara More articles by this author , Johan StyrkeJohan Styrke More articles by this author , Ingela Franck LissbrantIngela Franck Lissbrant More articles by this author , and Rolf GedeborgRolf Gedeborg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002570.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patient selection and time on treatment with abiraterone for de novo metastatic castration sensitive prostate cancer (mCSPC) may be different in clinical practice compared to randomised clinical trials, since men in RCTs are generally younger and fitter than men treated in clinical practise. However, to date there are no data on time on treatment with abiraterone in men with de novo mCSPC from clinical practise. METHODS: In this nation-wide population-based study, The National Prostate Cancer Register of Sweden was linked to the Patient Register and the Prescribed Drug Register. We estimated time on treatment with abiraterone in men with de novo mCSPC who had been diagnosed between 1 June 2018 and 31 December 2019. The cumulative incidence of treatment discontinuation was calculated considering death as competing risk. RESULTS: Out of 1511 men with de novo mCSPC diagnosed during the study period, 12% initiated treatment with abiraterone within 6 months from prostate cancer diagnosis. These men were younger, had higher Gleason score, higher prostate-specific antigen, but less comorbidity, compared to men with de novo mCSPC not treated with abiraterone. After a median follow-up of 14 months, the median time on treatment with abiraterone was 14 months, which is substantially shorter compared to median time on treatment of 26-33 months reported in RCTs. The shorter time on treatment did not appear to be due to high mortality. CONCLUSIONS: During the early post marketing period, the time on treatment with abiraterone for de novo metastatic castration sensitive prostate cancer was almost two-fold shorter compared to what was reported from RCTs. Further studies are warranted to investigate the reasons for discontinuation of abiraterone and to investigate the consequences of the shorter treatment time on outcome. Source of Funding: Swedish Cancer Society © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e449 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pär Stattin More articles by this author Hans Garmo More articles by this author Camilla Thellenberg-Karlsson More articles by this author Giuseppe Fallara More articles by this author Johan Styrke More articles by this author Ingela Franck Lissbrant More articles by this author Rolf Gedeborg More articles by this author Expand All Advertisement PDF DownloadLoading ...

Different fractionation schedules of radiotherapy to the primary tumor in metastatic hormone sensitive prostate cancer (Hypo-M1).

TPS192 Background: Radiotherapy of the primary tumor in metastatic prostate cancer is life-prolonging in patients with limited disease spread. Several different fractionation schedules have been used, most widely used is a four-week schedule of 2.75-3 Gy in 19-20 fractions. More data is emerging around hypo-fractionated radiotherapy in the curative setting. We hypothesize that a modified version of the Scandinavian Hypo-trial fractionation 6.1Gy per fraction x 6 fractions over a span of 2½ week will be non-inferior in side-effects as a 4-week schedule but more convenient for patients and caregivers. Methods: The Hypo-M1 trial is a randomized, stratified, multi-center, phase 3 clinical trial recruiting 420 patients in 9 Swedish centers. Key eligibility criteria include histological confirmed prostate cancer, indication for radiotherapy of low burden metastatic prostate cancer, defined as a max of 4 skeletal metastases at any site or lymph node metastases outside the pelvis and no other diseases or treatments interfering with radiotherapy or a score &gt; 20 on the International prostate symptom score (IPSS) scale. Patients will be randomized to either 3 Gy x 19 or 6.1Gy x 6. Stratification factors are T1-T3 vs T4 and randomizing centre. Type of staging procedures performed, CT and whole-body bone scan is recommended, PSMA-PET allowed and further treatment beyond ADT is recorded but not stratification variables. Standard treatment may include docetaxel, apalutamide, abiraterone and enzalutamide at the treating physician’s discretion. Toxicity will be measured before, at the end of radiotherapy and at 1, 3, 6, 12 months and at 3 years. Measures used are the CTCAE v 5.0 and RTOG scales and QoL life will be measured at the same time points with the Prostate Cancer Symptom Scale (PCSS), a validated QoL instrument focusing on prostate cancer radiotherapy. The primary endpoint is QoL at 3 months and key secondary is acute toxicity at 3 months, late toxicity and QoL at 12 months, failure free survival and cause specific survival. The sample size is calculated for a continuous outcome non-inferiority trial with a one-sided alpha-value of 2.5 % and a beta-value of 80 %. The non-inferiority limit is set to 7.5 % This will require 175 patients with complete follow up in each treatment arm. Expecting a response rate of 80 % for the PCSS at the main time end point the total number of patients in each arm will be 210. The National Prostate Cancer Registry, covering 98% of all prostate cancer cases in Sweden, will be used as CRF including also a randomization module, making this a truly population based clinical trial. As of October 12, 2021, accrual is set to begin in December. The Hypo-M1 trial is an investigator-led, academic trial sponsored by the Swedish Society of Urological Oncology with study coordination provided by Cancer Center of Umeå University Hospital, Umeå, Sweden. Clinical trial information: NCT04612907.

Prognostic Utility of the Gleason Grading System Revisions and Histopathological Factors Beyond Gleason Grade.

BackgroundThe International Society of Urological Pathology (ISUP) revised the Gleason system in 2005 and 2014. The impact of these changes on prostate cancer (PCa) prognostication remains unclear.ObjectiveTo evaluate if the ISUP 2014 Gleason score (GS) predicts PCa death better than the pre-2005 GS, and if additional histopathological information can further improve PCa death prediction.Patients and MethodsWe conducted a case–control study nested among men in the National Prostate Cancer Register of Sweden diagnosed with non-metastatic PCa 1998–2015. We included 369 men who died from PCa (cases) and 369 men who did not (controls). Two uro-pathologists centrally re-reviewed biopsy ISUP 2014 Gleason grading, poorly formed glands, cribriform pattern, comedonecrosis, perineural invasion, intraductal, ductal and mucinous carcinoma, percentage Gleason 4, inflammation, high-grade prostatic intraepithelial neoplasia (HGPIN) and post-atrophic hyperplasia. Pre-2005 GS was back-transformed using i) information on cribriform pattern and/or poorly formed glands and ii) the diagnostic GS from the registry. Models were developed using Firth logistic regression and compared in terms of discrimination (AUC).ResultsThe ISUP 2014 GS (AUC = 0.808) performed better than the pre-2005 GS when back-transformed using only cribriform pattern (AUC = 0.785) or both cribriform and poorly formed glands (AUC = 0.792), but not when back-transformed using only poorly formed glands (AUC = 0.800). Similarly, the ISUP 2014 GS performed better than the diagnostic GS (AUC = 0.808 vs 0.781). Comedonecrosis (AUC = 0.811), HGPIN (AUC = 0.810) and number of cores with ≥50% cancer (AUC = 0.810) predicted PCa death independently of the ISUP 2014 GS.ConclusionThe Gleason Grading revisions have improved PCa death prediction, likely due to classifying cribriform patterns, rather than poorly formed glands, as Gleason 4. Comedonecrosis, HGPIN and number of cores with ≥50% cancer further improve PCa death discrimination slightly.

Mortality in men with castration-resistant prostate cancer-A long-term follow-up of a population-based real-world cohort.

ObjectivesThe objective of this study is to find clinical variables that predict the prognosis for men with castration‐resistant prostate cancer (CRPC) in a Swedish real‐life CRPC cohort, including a risk group classification to clarify the risk of succumbing to prostate cancer. This is a natural history cohort representing the premodern drug era before the introduction of novel hormonal drug therapies.MethodsPSA tests from the clinical chemistry laboratories serving health care in six regions of Sweden were retrieved and cross‐linked to the National Prostate Cancer Registry (NPCR) to identify men with a prostate cancer diagnosis. Through further cross‐linking with data sources at the Swedish Board of Health and Welfare, we retrieved other relevant information such as prescribed drugs, hospitalizations, and cause of death. Men entered the CRPC cohort at the first date of doubling of their PSA nadir value with the last value being >2 ng/ml, or an absolute increase of >5 ng/ml or more, whilst on 3 months of medical castration or if they had been surgically castrated (n = 4098). By combining the two variables with the largest C‐statistics, “PSA at time of CRPC” and “PSA doubling time,” a risk group classification was created.ResultsPSA‐DT and PSA at date of CRPC are the strongest variables associated with PC specific survival. At the end of follow‐up, the proportion of men who died due to PC was 57%, 71%, 81%, 86%, and 89% for risk categories one through five, respectively. The median overall survival in our cohort of men with CRPC was 1.86 years (95% CI: 1.79–1.97).ConclusionFor a man with castration‐resistant prostate cancer, there is a high probability that this will be the main cause contributing to his death. However, there is a significant difference in mortality that varies in relation to tumor burden assessed as PSA doubling time and PSA at time of CRCP. This information could be used in a clinical setting when deciding when to treat more or less aggressively once entering the CRPC phase of the disease.

Time on treatment with abiraterone and enzalutamide in the Patient-overview Prostate Cancer in The National Prostate Cancer Register of Sweden

Background There are little and inconsistent data from clinical practice on time on treatment with the androgen receptor-targeted drugs (ART) abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). We assessed time on treatment with ART and investigated predictors of time on treatment. Material and methods Time on treatment with ART in men with mCRPC in the patient-overview prostate cancer (PPC), a subregister of the National Prostate Cancer Register (NPCR) of Sweden, was assessed by use of Kaplan–Meier plots and Cox regression. To assess the representativity of PPC for time on treatment, a comparison was made with all men in NPCR who had a filling for ART in the Prescribed Drug Registry. Results 2038 men in PPC received ART between 2015 and 2019. Median time on treatment in chemo-naïve men was 10.8 (95% confidence interval 9.1–13.1) months for abiraterone and 14.1 (13.5–15.5) for enzalutamide. After the use of docetaxel, time on treatment was 8.2 (6.5–12.4) months for abiraterone and 11.1 (9.8–12.6) for enzalutamide. Predictors of a long time on treatment with ART were long duration of ADT prior to ART, low serum levels of PSA at start of ART, absence of visceral metastasis, good performance status, and no prior use of docetaxel. PPC captured 2522/6337 (40%) of all men in NPCR who had filled a prescription for ART. Based on fillings in the Prescribed Drug Registry, men in PPC had a slightly longer median time on treatment with ART compared to all men in NPCR, 9.6 (9.1–10.3) vs. 8.6 (6.3–9.1) months. Conclusions Time on treatment in clinical practice was similar or shorter than that in published RCTs, due to older age, poorer performance status and more comorbidities.

The 90‐day cause‐specific mortality after radical prostatectomy: a nationwide population‐based study

To investigate the cause-specific mortality in the postoperative period after radical prostatectomy (RP) for prostate cancer (PCa). In the National Prostate Cancer Register of Sweden (NPCR), we identified all men who died within 90 days after RP performed 1998-2018 and we assessed cause of death in a chart review. We compared the adjudications of death from our medical record review with those in in the Swedish Cause of Death Registry (CDR). Out of 44 635, 58 (0.13%) men who had undergone RP from 1998 through 2018 died within 90 days after RP. Per medical record review the most common causes of death were cardiac disease (30%) and venous thromboembolic events (VTE; 21%). No men died of metastatic PCa as was first indicated in the CDR. After robot-assisted RP (RARP) or open retropubic RP (RRP), the postoperative mortality was 0.09% (19/21 520) and 0.19% (37/19 635), respectively. The effect off modality was confounded mainly by year of surgery, age at surgery, Charlson Comorbidity Index score and the concomitant pelvic lymph node dissection. The validated absolute 90-day mortality after RP was 1.3/1000 during the 21-year study period. Cardiovascular diseases were the most common causes of death after RP. Our validation of the CDR refuted the occurrence of postoperative deaths from metastatic PCa. There were differences in rates and type of mortality between RRP and RARP, but the RARP cohort was more recent than the RRP cohort, which likely explain the differences.

Association of surgeon and hospital volume with short-term outcomes after robot-assisted radical prostatectomy: Nationwide, population-based study.

Background and objectiveFew studies have investigated the association between surgical volume and outcome of robot-assisted radical prostatectomy (RARP) in an unselected cohort. We sought to investigate the association between surgical volume with peri-operative and short-term outcomes in a nation-wide, population-based study group.Methods9,810 RARP’s registered in the National Prostate Cancer Register of Sweden (2015–2018) were included. Associations between outcome and volume were analyzed with multivariable logistic regression including age, PSA-density, number of positive biopsy cores, cT stage, Gleason score, and extent of lymph node dissection.ResultsSurgeons and hospitals in the highest volume group compared to lowest group had shorter operative time; surgeon (OR 9.20, 95% CI 7.11–11.91), hospital (OR 2.16, 95% CI 1.53–3.06), less blood loss; surgeon (OR 2.58. 95% CI 2.07–3.21) hospital (no difference), more often nerve sparing intention; surgeon (OR 2.89, 95% CI 2.34–3.57), hospital (OR 2.02, 95% CI 1.66–2.44), negative margins; surgeon (OR 1.90, 95% CI 1.54–2.35), hospital (OR 1.28, 95% CI 1.07–1.53). There was wide range in outcome between hospitals and surgeons with similar volume that remained after adjustment.ConclusionsHigh surgeon and hospital volume were associated with better outcomes. The range in outcome was wide in all volume groups, which indicates that factors besides volume are of importance. Registration of surgical performance is essential for quality control and improvement.

P0863 - Time on treatment with abiraterone and enzalutamide in the patient-overview prostate cancer in the national prostate cancer register of Sweden

Background There are little and inconsistent data from clinical practice on time on treatment with the androgen receptor-targeted drugs (ART) abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). We assessed time on treatment with ART and investigated predictors of time on treatment. Material and methods Time on treatment with ART in men with mCRPC in the patient-overview prostate cancer (PPC), a subregister of the National Prostate Cancer Register (NPCR) of Sweden, was assessed by use of Kaplan-Meier plots and Cox regression. To assess the representativity of PPC for time on treatment, a comparison was made with all men in NPCR who had a filling for ART in the Prescribed Drug Registry. Results 2038 men in PPC received ART between 2015 and 2019. Median time on treatment in chemo-naive men was 10.8 (95% confidence interval 9.1-13.1) months for abiraterone and 14.1 (13.5-15.5) for enzalutamide. After the use of docetaxel, time on treatment was 8.2 (6.5-12.4) months for abiraterone and 11.1 (9.8-12.6) for enzalutamide. Predictors of a long time on treatment with ART were long duration of ADT prior to ART, low serum levels of PSA at start of ART, absence of visceral metastasis, good performance status, and no prior use of docetaxel. PPC captured 2522/6337 (40%) of all men in NPCR who had filled a prescription for ART. Based on fillings in the Prescribed Drug Registry, men in PPC had a slightly longer median time on treatment with ART compared to all men in NPCR, 9.6 (9.1-10.3) vs. 8.6 (6.3-9.1) months. Conclusions Time on treatment in clinical practice was similar or shorter than that in published RCTs, due to older age, poorer performance status and more comorbidities.