Prostate Cancer Database Research Articles

Temporal changes in survival in men with de novo metastatic prostate cancer: nationwide population-based study

Background: There have been large changes in the pattern of detection, work-up and treatment of men with prostate cancer during the last two decades. Therefore, we aimed to investigate temporal changes in survival in men with metastatic prostate cancer.Methods: Population-based cohort study in Prostate Cancer data Base Sweden of 13,709 men with de novo metastatic prostate cancer diagnosed between 1998 and 2015. Overall survival in four calendar periods were compared by the use of Kaplan–Meier analyses and Cox regression models including age at diagnosis, T stage and serum levels of prostate-specific antigen (PSA).Results: Between 1998–2001 and 2010–2015, median survival increased with 6 months for all men. The largest increase in survival was 14 months in men age 60–69 at diagnosis and in multivariable analysis risk of death decreased for men diagnosed in 2010–2015 compared to 1998–2001, hazard ratio (HR) 0.77 (95% CI: 0.68–0.86). The median PSA at date of diagnosis decreased with 46% from 181 ng/mL in 1998 to 98 ng/mL in 2015.Conclusions: There was an increase in survival among men with de novo metastatic prostate cancer in Sweden between 1998 and 2015. This increase was due to a decreased cancer extent indicated by lower PSA levels with ensuing longer lead times and speculatively also due to an increased use of chemotherapy in the latest time period. Given the increasing use of systemic treatment for advanced prostate cancer, our results are likely heralding larger increases in survival in men with metastatic prostate cancer in the near future.

Undetectable PSA after radical prostatectomy is more likely in low burden N+ prostate cancer patients when an extended lymph node dissection is performed

ObjectivesTo analyze the likelihood of undetectable PSA (<0.01 ng/mL) after extended (ePLND) versus standard pelvic lymph-nodes dissection (sPLND) in pN+ patients. Materials and MethodsThe institutional prospectively maintained Prostate Cancer Database was queried for patients who underwent radical prostatectomy with PLND and were found with three or less lymph-nodal metastases between 2007 and 2017. The extension of the PLND was defined according to the number of lymph-nodes (LN) removed. Patients in the 75th or higher percentile of lymph-nodes removed were considered as the ePLND group; patients in the 25th or lower percentile in the sPLND group. Groups were compared in clinical and pathological variables. Student t-test was used for comparing continuous variables; chi-square test was used for categorical variables. Multivariable logistic regression assessed the probability of undetectable PSA at 3rd month postoperatively. Kaplan–Meier method estimated the probability of biochemical recurrence. Differences between the groups were compared by Log-rank test. Results1478 patients were treated within the time span considered. 95 with 1–3 lymph-nodal metastases were extracted. After accounting for inclusion criteria, 23 patients with a median of 11 L N removed were included in the sPLND group (25th percentile); 23 patients with >27 L N were included in ePLND group (75th percentile). Surgical time was longer for ePLND. Sixteen patients (69.6%) who underwent ePLND had undetectable PSA postoperatively. At multivariable analysis, the probability of undetectable PSA at 3rd month was higher in patients who received an ePLND (HR = 5.18; IC95% = 1.16–23.11; p = 0.03). ConclusionsePLND is more likely to predict undetectable PSA at third month after radical prostatectomy, irrespective of disease characteristics.

Comparison of various continence definitions in a large group of patients undergoing radical prostatectomy: a multicentre, prospective study

BackgroundDue to the usage of various measurement methods and definitions, comparing continence rates after radical prostatectomy is a challenging task. This study compares continence rates based on different methods and aims to identify the definition for continence which agrees best with the patients’ subjective assessment of continence.Additionally, continence was controlled for multiple influencing factors.MethodsThis prospective multicentre study was carried out in seven hospitals throughout Germany. Before and at 3, 6, and 12 months after surgery self-reporting questionnaires were completed and returned by 329 (84.4%) of 390 eligible patients. The questionnaires were independently evaluated and analysed by a third party. Association of continence with demographic, operative, and tumour factors in an ongoing comprehensive prostate cancer database was evaluated.ResultsThe continence rate drops substantially for patients undergoing radical prostatectomy but increases again with time. Concrete numbers vary considerably depending on definition – 44% at 3 months and 68% at 12 months after surgery (0 pads) vs. 71 and 90% (0–1 pads). Significant confounding variables regarding continence rate are nerve-sparing procedure, categorized Gleason score, rehabilitative cure treatment, and pelvic floor training.The definition of 0 pads for continence coincides greater than 0–1 pads with the patients’ self-assessment of being continent.ConclusionA standardized definition for continence would be desirable, as it is one of the most important preconditions to guarantee sound comparison of continence rates. Since there are enough other factors that make comparison difficult, we suggest using the definition of “0 pads”. It is easily measured objectively, leaves no room for interpretation, and agrees best with the patients’ self-assessment.

Abstract 2772: Recurrent alterations of the TenascinC in highly aggressive neuroendocrine sub-type of prostate cancer

Abstract Introduction: Early detection and prognosis of prostate cancer (CaP) is challenging due to its wide spectrum of biological features. Multi-analytic prognostic marker panels have increased sensitivity than single analytes among the biopsy tests and require advanced bioinformatics platform. We aimed to develop a panel of serum biomarkers using multi-omics approach and further characterized their involvement in prostate cancer progression. In a collaborative study between CPDR, Department of Surgery, USU and Berg Health, serum samples (N=385) were examined by multi-omics (proteomics, lipidomics and metabolomics) and Tenascin C (TNC) was identified as one of the promising markers for disease progression in combination with three other analytes, Apolipoprotein AIV, 1-Methyladenosine and a phosphatidic acid (PA 18:0-22:0). The combination of two clinical features, pathological measurement of T-Stage and Gleason score, along with the four molecular analytes further increased the AUC to 0.89 with a NPV of 0.96 and an odds ratio of 12.4. TNC, an extracellular matrix protein, is poorly studied in prostate cancer, though it is expressed in several cancer tissues such as the breast, lung, colon, and the gastrointestinal tract. Methods: Publically available prostate cancer databases (cBioportal Version 1.17.1, http://www.cbioportal.org/index.do) were queried for TNC, and known driver oncogenes in prostate cancer, ERG, AR and MYC. Results: Publically available prostate cancer databases (cBioPortal) demonstrated alterations (either amplifications or mutations) in TNC in 10 out of 16 datasets. Query of TNC along with the driver oncogenes of prostate tumorigenesis, including ERG, MYC and AR, in the aggressive neuroendocrine prostate cancer (NEPC) tumor whole genome sequencing datasets (N=77) demonstrating significant alterations (predominantly amplifications) in 74% of patient samples. CaP genomic levels TNC (30%) was significantly co-amplified (P &amp;lt; 0.001) with ERG (27%), AR (56%) and MYC (53%). TNC protein expression was detected in all examined prostate cancer cell lines VCaP, LNCaP, PC3 and DU145. Conclusion: Genomic alterations of TNC was thus associated with major oncogenic drivers of CaP, such as ERG, AR and MYC in NEPC genomic datasets. Multi-analyte serum biomarkers offers new opportunities with potential impact on primary treatment and surveillance strategies. Functional involvement of the analytes in disease progression to address their mechanistic link with major CaP oncogenic pathways will be further investigated. Citation Format: Prachi Mishra, Michael Kebish, Jennifer Cullen, Amina Ali, Alagasamy Srinivasan, Inger Rosner, David McLeod, Leonardo Rodrigues, Viatcheslav Akmaev, Rangaprasad Sarangarajan, Shiv Srivastava, Niven Narain, Albert Dobi. Recurrent alterations of the TenascinC in highly aggressive neuroendocrine sub-type of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2772.

Chronic inflammatory diseases, anti-inflammatory medications and risk of prostate cancer: a population-based case-control study

BackgroundWhether chronic inflammation increases prostate cancer risk remains unclear. This study investigated whether chronic inflammatory diseases (CID) or anti-inflammatory medication use (AIM) were associated with prostate cancer risk.MethodsFifty-five thousand nine hundred thirty-seven cases (all prostate cancer, 2007–2012) and 279,618 age-matched controls were selected from the Prostate Cancer Database Sweden. CIDs and AIMs was determined from national patient and drug registers. Associations were investigated using conditional logistic regression, including for disease/drug subtypes and exposure length/dose.ResultsMen with a history of any CID had slightly increased risk of any prostate cancer diagnosis (OR: 1.08; 95%CI: 1.04–1.12) but not ‘unfavourable’ (high-risk or advanced) prostate cancer. Generally, risk of prostate cancer was highest for shorter exposure times. However, a positive association was observed for asthma > 5 years before prostate cancer diagnosis (OR: 1.21; 95%CI: 1.05–1.40). Risk of prostate cancer was increased with prior use of any AIMs (OR: 1.26; 95%CI: 1.24–1.29). A positive trend with increasing cumulative dose was only observed for inhaled glucocorticoids (p < 0.011).ConclusionDetection bias most likely explains the elevated risk of prostate cancer with prior history of CIDs or use of AIMs, given the higher risk immediately after first CID event and lack of dose response. However, findings for length of time with asthma and dose of inhaled glucocorticoids suggest that asthma may increase risk of prostate cancer through other pathways.

Frecuencia de PSA indetectable en pacientes con cáncer de próstata N+ baja carga tras prostatectomía radical y linfadenectomía ampliada

ObjectivesTo analyze the likelihood of undetectable PSA (< 0.01 ng/mL) after extended (ePLND) versus standard pelvic lymph-nodes dissection (sPLND) in pN+ patients. Materials and methodsThe institutional prospectively maintained Prostate Cancer Database was queried for patients who underwent radical prostatectomy with PLND and were found with 3or less lymph-nodal metastases between 2007 and 2017. The extension of the PLND was defined according to the number of lymph-nodes (LN) removed. Patients in the 75th or higher percentile of lymph-nodes removed were considered as the ePLND group; patients in the 25th or lower percentile in the sPLND group. Groups were compared in clinical and pathological variables. Student T-test was used for comparing continuous variables; chi-square test was used for categorical variables. Multivariable logistic regression assessed the probability of undetectable PSA at 3rd month postoperatively. Kaplan-Meier method estimated the probability of biochemical recurrence. Differences between the groups were compared by Log-rank test. Results1478 patients were treated within the time span considered. 95 with 1 to 3 lymph-nodal metastases were extracted. After accounting for inclusion criteria, 23 patients with a median of 11 LN removed were included in the sPLND group (25th percentile); 23 patients with > 27 LN were included in ePLND group (75th percentile). Surgical time was longer for ePLND. Sixteen patients (69.6%) who underwent ePLND had undetectable PSA postoperatively. At multivariable analysis, the probability of undetectable PSA at 3rd month was higher in patients who received an ePLND (HR=5.18; IC 95%=1.16–23.11; P=.03). ConclusionsePLND is more likely to predict undetectable PSA at third month after radical prostatectomy, irrespective of disease characteristics.

How to measure temporal changes in care pathways for chronic diseases using health care registry data

BackgroundDisease trajectories for chronic diseases can span over several decades, with several time-dependent factors affecting treatment decisions. Thus, there is a need for long-term predictions of disease trajectories to inform patients and healthcare professionals on the long-term outcomes and provide information on the need of future health care. Here, we propose a state transition model to describe and predict disease trajectories up to 25 years after diagnosis in men with prostate cancer (PCa), as a proof of principle.MethodsStates, state transitions, and transition probabilities were identified and estimated in Prostate Cancer data Base of Sweden (PCBaSeTraject), using nationwide population-based data from 118,743 men diagnosed with PCa. A state transition model in discrete time steps (i.e., 4 weeks) was developed and applied to capture all possible transitions (PCBaSeSim). Transition probabilities were estimated for changes in both treatment and comorbidity. These models combined yielded parameter estimates to run an individual-level simulation based on the state-transition model to obtain prediction estimates. Predicted estimates were then compared to real world data in PCBaSeTraject.ResultsPCBaSeSim estimates for the cumulative incidence of first and second transitions, death from PCa and death from other causes were compared to observed transitions in PCBaSeTraject. A good agreement was found between simulated and observed estimates.ConclusionsWe developed a reliable and accurate simulation tool, PCBaSeSim that provides information on disease trajectories for subjects with a chronic disease on an individual and population-based level.

164 - External validation of the PREDICT Prostate tool for prognostication in non-metastatic prostate cancer: A study in 69,206 men from prostate cancer data base Sweden

164 - External validation of the PREDICT Prostate tool for prognostication in non-metastatic prostate cancer: A study in 69,206 men from prostate cancer data base Sweden

An overview of publicly available patient-centered prostate cancer datasets.

Prostate cancer (PCa) is the second most common cancer in men, and the second leading cause of death from cancer in men. Many studies on PCa have been carried out, each taking much time before the data is collected and ready to be analyzed. However, on the internet there is already a wide range of PCa datasets available, which could be used for data mining, predictive modelling or other purposes, reducing the need to setup new studies to collect data. In the current scientific climate, moving more and more to the analysis of "big data" and large, international, multi-site projects using a modern IT infrastructure, these datasets could be proven extremely valuable. This review presents an overview of publicly available patient-centered PCa datasets, divided into three categories (clinical, genomics and imaging) and an "overall" section to enable researchers to select a suitable dataset for analysis, without having to go through days of work to find the right data. To acquire a list of human PCa databases, scientific literature databases and academic social network sites were searched. We also used the information from other reviews. All databases in the combined list were then checked for public availability. Only databases that were either directly publicly available or available after signing a research data agreement or retrieving a free login were selected for inclusion in this review. Data should be available to commercial parties as well. This paper focuses on patient-centered data, so the genomics data section does not include gene-centered databases or pathway-centered databases. We identified 42 publicly available, patient-centered PCa datasets. Some of these consist of different smaller datasets. Some of them contain combinations of datasets from the three data domains: clinical data, imaging data and genomics data. Only one dataset contains information from all three domains. This review presents all datasets and their characteristics: number of subjects, clinical fields, imaging modalities, expression data, mutation data, biomarker measurements, etc. Despite all the attention that has been given to making this overview of publicly available databases as extensive as possible, it is very likely not complete, and will also be outdated soon. However, this review might help many PCa researchers to find suitable datasets to answer the research question with, without the need to start a new data collection project. In the coming era of big data analysis, overviews like this are becoming more and more useful.

Biochemical Recurrence Prediction after Radical Prostatectomy Using Korean Prostate Cancer Registry Database

Objectives: As the surgical techniques are developed such as adopting robotic surgery etc. It has been reduced postoperative side effects such as urinary incontinence and sexual dysfunction etc., but also remain constant risk of recurrence after the treatment. It is very important to figure out the predictive factors, whichincreasing the probability of long-term survival, by Analyzing the progression of the disease according to biochemical recurrence (BCR). This study aims to figure out the influential predictive factors on BCR by using Korean Prostate Cancer Registry (KPCR) database, which constructedwith providing data from Korean manifold, because of therecurrence-free survival rates are reported to vary according to geographical location and race. Methods: KPCR database consists 7,394 patients’ data which collected from six medical institutions, and final analysis was conducted with 5,119 patients’ data which collected from December 2003 to December 2014. Statistical analysis was conducted with the multivariable Cox proportional hazard regression models to figure out the correlation of clinical factors which affect BCR. The biochemical recurrence free survival rate (BCR-FS) was calculated using with Kaplan-Meier method. Results: The 5 year BCR occurred in 23.6% (1,209 patients). As a result of the recurrence rate, prostate specific antigen (PSA) value ≥20.1 ng/mL was 49.3%, the clinical T3 stage was 40.4%, Gleason score ≥8 was 54.4%, Gleason score 7 was 21.8%. The mean duration of BCR was 20.7 months and the strongest predictor of BCR was Gleason scoreand PSA value ≥20.1 ng/mL. Conclusions: It has been verified that, Gleason scores and PSA value are the most influential factors for biochemical recurrence after radical prostatectomy. These results will be helpful fordetermining the treatment direction in postoperative follow-up and able to contribute to improving survival outcome in the future. Key words: Prostatic neoplasms, Prostatectomy, Biochemical recurrence, Prostate cancer database

Androgen deprivation therapy for prostate cancer and risk of dementia.

ObjectivesTo study whether androgen deprivation therapy (ADT), the mainstay treatment for advanced and disseminated prostate cancer, is associated with risk of dementia.MethodsRisk of dementia in men with prostate cancer primarily managed with ADT or watchful waiting (WW) in the Prostate Cancer Database Sweden, PCBaSe, was compared with that in prostate cancer‐free men, matched on birth year and county of residency. We used Cox regression to calculate the hazard ratios (HRs) for Alzheimer's and non‐Alzheimer's dementia (vascular dementia, dementia secondary to other diseases or unspecified dementias) for different types and duration of ADT and oral antiandrogens (AAs) as well as for men managed with WW.ResultsA total of 25 967 men with prostate cancer and 121 018 prostate cancer‐free men were followed for a median of 4 years. In both groups 6% of the men were diagnosed with dementia. In men with prostate cancer, gonadotropin‐releasing hormone agonist treatment ( HR 1.15, 95% confidence interval [CI] 1.07–1.23) and orchiectomy (HR 1.60, 95% CI 1.32–1.93) were associated with an increased risk of dementia, as compared to no treatment in prostate cancer‐free men; however, this increase in risk was only observed for non‐Alzheimer's dementia and occurred from year 1–4 after start of ADT. No increase in risk for any type of dementia was observed for men treated with AAs or for men on WW.ConclusionThis population‐based cohort study does not support previous observations of an increased risk of Alzheimer's dementia for men on ADT; however, there was a small increase in risk of non‐Alzheimer's dementia.

BRG1 is a prognostic indicator and a potential therapeutic target for prostate cancer.

Brahma‐related gene 1 (BRG1) is one of two mutually exclusive ATPases that function as the catalytic subunit of human SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling enzymes. BRG1 has been identified as a tumor suppressor in some cancer types but has been shown to be expressed at elevated levels, relative to normal tissue, in other cancers. Using TCGA (The Cancer Genome Atlas) prostate cancer database, we determined that BRG1 mRNA and protein expression is elevated in prostate tumors relative to normal prostate tissue. Only 3 of 491 (0.6%) sequenced tumors showed amplification of the locus or mutation in the protein coding sequence, arguing against the idea that elevated expression due to amplification or expression of a mutant BRG1 protein is associated with prostate cancer. Kaplan‐Meier survival curves showed that BRG1 expression in prostate tumors inversely correlated with survival. However, BRG1 expression did not correlate with Gleason score/International Society of Urological Pathology (ISUP) Grade Group, indicating it is an independent predictor of tumor progression/patient outcome. To experimentally assess BRG1 as a possible therapeutic target, we treated prostate cancer cells with a biologic inhibitor called ADAADi (active DNA‐dependent ATPase A Domain inhibitor) that targets the activity of the SNF2 family of ATPases in biochemical assays but showed specificity for BRG1 in prior tissue culture experiments. The inhibitor decreased prostate cancer cell proliferation and induced apoptosis. When directly injected into xenografts established by injection of prostate cancer cells in mouse flanks, the inhibitor decreased tumor growth and increased survival. These results indicate the efficacy of pursuing BRG1 as both an indicator of patient outcome and as a therapeutic target.

Survival after biochemical failure in prostate cancer treated with radiotherapy: Spanish Registry of Prostate Cancer (RECAP) database outcomes.

The clinical course in patients with prostate cancer (PCa) after biochemical failure (BF) has received limited attention. This study analyzes survival time from recurrence, patterns of progression, and the efficacy of salvage therapies in patients treated with radical or postoperative radiotherapy (RT). This is a multicenter retrospective comparative study of 1135 patients diagnosed with BF and treated with either radical (882) or postoperative (253) RT. Data correspond to the RECAP database. Clinical, tumor, and therapeutic characteristics were collected. Descriptive statistics, survival estimates, and comparisons of survival rates were calculated. Time to BF from initial treatment (RT or surgery) was higher in irradiated patients (51 vs 37months). At a median follow-up of 102months (14-254), the 8-year cause-specific survival (CSS) was 80.5%, without significant differences between the radical (80.1%) and postoperative (83.4%) RT groups. The 8-year metastasis-free survival rate was 57%. 173 patients (15%) died of PCa and 29 (2.5%) of a second cancer. No salvage therapy was given in 15% of pts. Only 5.5% of pts who underwent radical RT had local salvage treatment and 71% received androgen deprivation (AD) ± chemotherapy. The worst outcomes were in patients who developed metastases after BF (302pts; 26.5%) and in cases with a Gleason > 7. In PCa treated with radiotherapy, median survival after BF is relatively long. In this sample, no differences in survival rates at 8-years have been found, regardless of the time of radiotherapy administered. AD was the most common treatment after BF. Metastases and high Gleason score are adverse variables. To our knowledge, this is the first study to compare outcomes after BF among patients treated with primary RT vs. those treated with postoperative RT and to evaluate recurrence patterns, treatments administered, and causes of death. The results allow avoiding overtreatment, improving quality of life, without negatively affecting survival.

MicroRNA-135a induces prostate cancer cell apoptosis via inhibition of STAT6.

Clinical management of metastatic prostate cancer remains a challenge. Activation of apoptosis signaling pathways via signal transducer and activator of transcription 6 (STAT6) has been hypothesized to be a therapeutic strategy for patients with metastatic prostate cancer. The ONCOMINE® prostate cancer database and two Gene Expression Omnibus datasets (Gene Series 40026 and 21032) were re-analyzed to determine the expression levels of STAT6 and microRNA (miR)-135a in prostate cancer. The current study investigated the induced overexpression of miR-135a in prostate cancer cell lines to detect its function in prostate cell apoptosis using Hoechst staining and fluorescence-activated cell sorting and examined the expression levels of STAT6 and its DNA binding ability using western blotting and an electrophoretic mobility shift assay. In analysis of the ONCOMINE® database, STAT6 expression levels in prostate cancer tissue were higher compared with those in normal prostate gland tissue and were associated with the overall survival rate and biochemical relapse rate following radical prostatectomy. Additionally, there was an inverse correlation between miR-135a and STAT6 expression levels in prostate cancer cell lines. miR-135a was able to induce prostate cancer cell apoptosis via targeting STAT6 mRNA and subsequently repressing protein expression and phosphorylation, which also altered the transcriptional factor function of STAT6 through its DNA-binding capabilities. In conclusion, miR-135a may function as a tumor-suppressing miRNA in prostate cancer and its anti-oncogenic activity may involve the direct targeting and inhibition of STAT6.

Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer

BackgroundSome studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias. ObjectiveTo investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study. Design, setting, and participantsMen with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n=2078) or GnRH agonists (n=4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5yr before through to 5yr after starting androgen deprivation therapy (ADT). Outcome measures and statistical methodsMultivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses. Results and limitationsMen on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p<0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20–1.44). ConclusionsImpact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment. Patient summaryHormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.

Anti-androgen monotherapy versus gonadotropin-releasing hormone agonists in men with advanced, non-metastatic prostate cancer: a register-based, observational study

Background: In randomised controlled trials, men with advanced, non-metastatic prostate cancer (PCa) treated with anti-androgen monotherapy (AA) had similar all-cause mortality as men treated with gonadotropin-releasing hormone (GnRH) agonists. Using real-world evidence (i.e., observational data), we aimed to further assess the difference in mortality between these two drug categories.Material and Methods: We emulated a trial using data from Prostate Cancer data Base Sweden 3.0. We specifically focused on men diagnosed in 2006–2012 with high-risk PCa who had no distant metastasis. They either received primary hormonal therapy with AA (n = 2078) or GnRH agonists (n = 4878) who were followed for a median time of 5 years. Risk of death from PCa and other causes was assessed using competing risk analyses and Cox proportional hazards regression analyses, including propensity score matching.Results: The cumulative 5-year PCa mortality was lower for men treated with AA (16% [95% confidence interval, CI, 15–18%]) than men treated with GnRH agonists (22% [95% CI 21–24%]). The 5-year other cause mortality was also lower for men on AA (17% [95% CI 15–19%] compared to men on GnRH agonists (27% [95% CI 25–28%]). In regression analyses, the risk of PCa death was similar, GnRH agonists versus AA (reference), hazard ratio (HR) 1.08 (95% CI 0.95–1.23), but the risk of death from all causes was higher for men on GnRH agonists, HR 1.23 (95% CI 1.13–1.34). Consistent results were seen in the propensity score-matched cohort.Conclusion: Our results indicate that the use of AA as primary hormonal therapy in men with high-risk non-metastatic PCa does not increase PCa-specific mortality compared to GnRH. Using AA instead of GnRH agonists may result in shorter time on/exposure to GnRH-treatment, which may reduce the risk of adverse events associated with this treatment.

Automated Text Mining of Prostate Pathology Reports Extracted from an Electronic Medical System, using a Rule-Based Approach

Retrospective analysis of large-scale, prostate cancer databases to identify trends in cancer care and outcomes require detailed histopathologic characterization. Manual extraction of these characteristics from prostate pathology reports is a time-consuming process that is prone to human error. Our goal was to develop a rule-based software algorithm that was capable of automatically extracting pertinent characteristics (primary and secondary Gleason grade, maximum core involvement, number of positive and total cores) from prostate pathology reports. Prostate pathology reports were manually extracted from our institution’s electronic medical record system for 135 patients. The dataset was split into a training and testing set consisting of 110 and 25 patients, respectively. The training set was examined by hand to identify patterns and linguistic features that could be used to build the rules for extracting the clinical characteristics. During the training phase, it was noted that a different set of rules was required for outside slide reviews as these often presented the results in summary format as opposed to the core-by-core breakdown of those authored at our institution. These rules were then implemented in the statistical software platform, R. The performance of the algorithm was assessed in both training and testing sets by comparing the software predictions of the clinical characteristics to those made by a human observer. Of the 135 pathology reports, 29 were outside slide reviews (23 in training, and 6 in testing). The algorithm was able to correctly identify the primary and secondary Gleason grade, as well as the maximum core involvement percentage in 100% (135/135) of the data set. Due to ambiguity in reporting, four of the reports were excluded for the total core analysis, while two were excluded for the positive core analysis. The algorithm correctly identified the total cores in 95% (124/131) of the data set and the positive cores in 98% (131/133) of the data set. The testing set accuracy for the total and positive cores was 83% (19/23) and 96% (23/24), respectively. Analysis of errors revealed that four of the seven incorrectly identified total cores and both incorrectly identified positive cores were in outside slide reviews. The rule-based software algorithm was able to correctly extract and identify the primary and secondary Gleason grades, maximum core involvement, and number of positive and total cores in the majority of the examined prostate pathology reports. Standardized reporting, including a core-by-core breakdown, may lead to improved accuracy of text-mining algorithms and mitigate the need for human registrars.

Late biochemical recurrence after radical prostatectomy is associated with a slower rate of progression.

To characterise the pattern of late biochemical recurrence (BCR) in the largest contemporary cohort of patients with localised prostate cancer treated with radical prostatectomy (RP) in the active surveillance era. Consecutive patients who underwent RP for localised prostate cancer between 2003 and 2017 were identified from a prospectively recorded, dedicated prostate cancer database. Patients who received neoadjuvant androgen-deprivation therapy were excluded. These patients were categorised into the following groups: no BCR, BCR at <12months (early), BCR at 12-60months (intermediate), and BCR at >60months (late), after RP. Clinicopathological characteristics were analysed using the Student's t-test, Mann-Whitney U-test, or chi-squared test where appropriate. Multivariable binomial logistic regression models were used to assess predictors of BCR at various time-points. In all, 2312 patients were included in the final analysis with up to 12years of follow-up data. The average patient had clinically localised prostate cancer, an elevated PSA level, and International Society of Urological Pathology (ISUP) Grade Group 2 on biopsy. In all, 88.7% of patients had ISUP Grade Group ≥2 at RP. A subgroup of 446 patients had undetectable PSA levels at 5years after RP; 11.7% of them progressed to experience BCR. In this subgroup, late recurrers had significantly higher-grade tumours on ISUP and Gleason sum (P <0.001 and P = 0.001, respectively), higher rates of extraprostatic extension (P = 0.022), and larger tumour volumes (P = 0.032). Logistic regression showed that RP ISUP Grade Group was a significant predictor of BCR (odds ratio 2.14, 95% confidence interval 1.43-3.20; P <0.001). This study characterises the pattern of late BCR in the largest contemporary active surveillance era cohort. We have identified that RP ISUP Grade Group is a strong predictive indicator for late BCR. We also propose that timing of BCR resides on a continuum of risk and that the potential concept of dormant micrometastatic involvement requires further research and evaluation.

Effects of age and comorbidity on survival vary according to risk grouping among patients with prostate cancer treated using radical prostatectomy

A multicenter Korean Prostate Cancer Database (K-CaP) has been established to provide information regarding Korean patients with prostate cancer (PCa). We used the K-CaP registry to investigate the value of age and comorbidity for predicting cancer-specific mortality (CSM) and other-cause mortality (OCM) according to risk grouping.The K-CaP registry includes 2253 patients who underwent radical prostatectomy (RP) between May 2001 and April 2013 at 5 institutions. Preoperative clinicopathologic data were collected and stratified according to the National Comprehensive Cancer Network risk criteria. Survival was evaluated using Gray's modified log-rank test according to risk category, age (<70 years vs ≥70 years), and Charlson comorbidity index (CCI) (0 vs ≥1).The median follow-up was 55.0 months (interquartile range: 42.0–70.0 months). Competing-risk regression analysis revealed that, independent of CCI, ≥70-year-old high-risk patients had significantly greater CSM than <70-year-old high-risk patients (P = .019). However, <70-year-old high-risk patients with a CCI of ≥1 had similar CSM relative to ≥70-year-old patients. Survival was not affected by age or CCI among low-risk or intermediate-risk patients. Multivariate analysis revealed that a CCI of ≥1 was independently associated with a higher risk of CSM (P = .003), while an age of ≥70 years was independently associated with a higher risk of OCM (P = .005).Age and comorbidity were associated with survival after RP among patients with high-risk PCa, although these associations were not observed among low-risk or intermediate-risk patients. Therefore, older patients with high-risk diseases and greater comorbidity may require alternative multidisciplinary treatment.

Heterogeneity in risk of prostate cancer: A Swedish population-based cohort study of competing risks and Type 2 diabetes mellitus.

Most previous studies of prostate cancer have not taken into account that men in the studied populations are also at risk of competing event, and that these men may have different susceptibility to prostate cancer risk. The aim of our study was to investigate heterogeneity in risk of prostate cancer, using a recently developed latent class regression method for competing risks. We further aimed to elucidate the association between Type 2 diabetes mellitus (T2DM) and prostate cancer risk, and to compare the results with conventional methods for survival analysis. We analysed the risk of prostate cancer in 126,482 men from the comparison cohort of the Prostate Cancer Data base Sweden (PCBaSe) 3.0. During a mean follow‐up of 6 years 6,036 men were diagnosed with prostate cancer and 22,393 men died. We detected heterogeneity in risk of prostate cancer with two distinct latent classes in the study population. The smaller class included 9% of the study population in which men had a higher risk of prostate cancer and the risk was stronger associated with class membership than any of the covariates included in the study. Moreover, we found no association between T2DM and risk of prostate cancer after removal of the effect of informative censoring due to competing risks. The recently developed latent class for competing risks method could be used to provide new insights in precision medicine with the target to classify individuals regarding different susceptibility to a particular disease, reaction to a risk factor or response to treatment.