Predict Prostate Cancer Death Research Articles

Other and All-Cause Mortality among Men Diagnosed with Prostate Cancer in the PLCO Trial

Men with prostate cancer have high cause-specific survival, and most deaths are from other causes. This study aimed to investigate other and all-cause mortality in a large cancer screening cohort. From the PLCO (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial cohort, we selected men diagnosed with prostate cancer from 1994-2014. We examined other and all-cause survival by prostate cancer risk level, defined as the D'Amico categories for localized disease (low, intermediate and high risk) plus nonlocalized disease. We developed 3 Cox proportional hazards models to assess the relationship between risk level and survival. Model I controlled for age, race, study arm and diagnosis year. Model II additionally controlled for other demographic and medical history factors. Model III additionally controlled for initial treatment. Of 76,672 men in PLCO and 10,859 prostate cancer cases, 9,248 (85.2%) had known prostate cancer risk level (mean±SD age 70.4±6.2 years). Median followup time from diagnosis was 10.8 years (IQR 6.8-15.0). Of 3,318 deaths 81% were from other causes. Compared to the low risk group, other-cause mortality HRs were 1.13 (95% CI 1.04-1.23), 1.35 (95% CI 1.21-1.50) and 1.63 (95% CI 1.35-1.97) for intermediate risk, high risk and advanced disease, respectively, in model II. Model III HRs were similar to model II except for advanced disease, where the HR decreased to 1.35. Other-cause survival was greater in lower vs higher risk disease, even after controlling for lifestyle characteristics and comorbidities. Further research is needed to identify factors contributing to this higher other-cause mortality to help mitigate the risk.

Abstract LB-149: Serum thymidine kinase 1 levels predict prostate cancer-specific survival

Abstract Background: Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis. Thymidine kinases phosphorylate thymidine as part of the DNA synthetic pathway. TK1 expression is a marker of active cellular proliferation; intracellular concentrations are low during the G0/G1 phases of the cell cycle, increasing during the S/G2 phases. Previous studies have suggested that serum TK1 levels could be used as marker for presence of prostate cancer (PCa). Here, we evaluated whether serum TK1 levels could predict risk of PCa prognosis. Materials and Methods: The study population included 40 men with clinically defined T1/T2NxM0 PCa and 43 men with de novo metastatic cancer (M1) at diagnosis confirmed by bone scan imaging. All men were diagnosed and treated at the Tampere University Hospital between 2000-2010. All men provided a serum sample at the time of diagnosis. Information on deaths and causes of death were obtained from national causes of death registry. Serum TK1 concentrations were determined using the AroCell TK210 ELISA kit. Cox regression and Kaplan-Meier Curves with adjustment for tumor risk group (Gleason-grade, TNM stage and PSA level) were used to evaluate the risk of PCa death in relation to TK1 levels (median or below vs. above median). ROC analyses were used to evaluate the predictive accuracy of PSA, TK1 and their combination. Results: M1 cases were older than M0 cases; median age 72 vs 62 years, respectively. M1 cases were mainly managed with androgen deprivation therapy, whereas M0 cases were most often managed with radical prostatectomy. Median serum TK1 levels were significantly higher among M1 cases compared to M0 cases (p for difference 0.001). In the combined study population, serum TK1 levels were a significant predictor of PCa-specific (HR 8.33, 95% CI 2.05-33.88) and overall mortality (HR 5.53, 95% CI 1.93-15.85) after adjustment for established prognostic factors including tumor risk group. Kaplan-Meier survival curves defined by TK1 level started to differ within 24 months from PCa diagnosis. In ROC analyses TK1 alone or in combination with PSA was no more accurate than PSA alone in predicting PCa death. Conclusion: The proliferation biomarker TK1 in serum predicted survival after PCa diagnosis, demonstrating independent predictive value over established clinical risk factors. If confirmed in further and larger studies, this biomarker could be incorporated in PCa risk stratification when selecting optimal treatment and surveillance schedule. Citation Format: Teemu J. Murtola, Paavo Raittinen, Teuvo Tammela. Serum thymidine kinase 1 levels predict prostate cancer-specific survival [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-149.

Predicting prostate cancer death among 98,994 veterans: Differences by race/ethnicity.

e17609 Background: Prostate cancer mortality is higher in Blacks than Whites, but existing prognostic indices fail to account for race/ethnicity. Using data from the national U.S. Veterans Affairs Healthcare System (VA), we compared prediction of prostate cancer death by race/ethnicity. Methods: Men with biopsy confirmed prostate cancer from 2002-2016 were included. We excluded those with lymph node or distant metastatic disease at diagnosis and those not classified as Non-Hispanic White (NHW), Non-Hispanic Black (NHB), or Hispanic (HSP). We set aside 20% for future validation. Cox models estimated hazard ratios (HR) for prostate cancer death, stratified by age and race/ethnicity. Each was adjusted for age, Gleason score, tumor (T) stage, PSA at diagnosis, and calendar year. Results: Among 98,994 veterans with localized disease, 64% were NHW, 30% were NHB, and 6% were HSP. At diagnosis, median age differed by race/ethnicity (NHW 66 [IQR 62-71] yrs.; NHB 63 [58-68] yrs.; HSP 66 [61-73] yrs.). During follow-up 23,316 men died, 3484 (15% overall, and by race/ethnicity) by prostate cancer. Among those < 65 yrs at diagnosis, HR for Gleason score were much stronger among NHW than NHB; associations for PSA level were stronger among NHB than NHW. HRs for HSP and NHW were similar. T stage HRs were similar by age and race/ethnicity. Conclusions: Risk associated with Gleason score and PSA varied by age and race/ethnicity. Prognostic models for prostate cancer disease progression must be evaluated in diverse populations and across age strata. [Table: see text]

Predicting Prostate Cancer Death with Different Pretreatment Risk Stratification Tools: A Head-to-head Comparison in a Nationwide Cohort Study

BackgroundNumerous pretreatment risk classification tools are available for prostate cancer. Which tool is best in predicting prostate cancer death is unclear. ObjectiveTo systematically compare the prognostic performance of the most commonly used pretreatment risk stratification tools for prostate cancer. Design, setting, and participantsA nationwide cohort study was conducted, including 154 811 men in Prostate Cancer data Base Sweden (PCBaSe) 4.0 diagnosed with nonmetastatic prostate cancer during 1998–2016 and followed through 2016. Outcome measurements and statistical analysisWe compared the D’Amico, National Institute for Health and Care Excellence (NICE), European Association of Urology (EAU), Genito-Urinary Radiation Oncologists of Canada (GUROC), American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), and Cambridge Prognostic Groups (CPG) risk group systems; the Cancer of the Prostate Risk Assessment (CAPRA) score; and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting prostate cancer death by estimating the concordance index (C-index) and the observed versus predicted cumulative incidences at different follow-up times. Results and limitationsA total of 139 515 men were included in the main analysis, of whom 15 961 died from prostate cancer during follow-up. The C-index at 10 yr of follow-up ranged from 0.73 (95% confidence interval [CI]: 0.72–0.73) to 0.81 (95% CI: 0.80–0.81) across the compared tools. The MSKCC nomogram (C-index: 0.81, 95% CI: 0.80–0.81), CAPRA score (C-index: 0.80, 95% CI: 0.79–0.81), and CPG system (C-index: 0.78, 95% CI: 0.78–0.79) performed the best. The order of performance between the tools remained in analyses stratified by primary treatment and year of diagnosis. The predicted cumulative incidences were close to the observed ones, with some underestimation at 5 yr. It is a limitation that the study was conducted solely in a Swedish setting (ie, case mix). ConclusionsThe MSKCC nomogram, CAPRA score, and CPG risk grouping system performed better in discriminating prostate cancer death than the D’Amico and D’Amico-derived systems (NICE, GUROC, EAU, AUA, and NCCN). Use of these tools may improve clinical decision making. Patient summaryThere are numerous pretreatment risk classification tools that can aid treatment decision for prostate cancer. We systematically compared the prognostic performance of the most commonly used tools in a large cohort of Swedish men with prostate cancer. The Memorial Sloan Kettering Cancer Center nomogram, Cancer of the Prostate Risk Assessment score, and Cambridge Prognostic Groups performed best in predicting prostate cancer death. The use of these tools may improve treatment decisions.

The percentage of high-grade prostatic adenocarcinoma in prostate biopsies significantly improves on Grade Groups in the prediction of prostate cancer death.

AimsIt has been recommended that the percentage of high‐grade (HG) Gleason patterns 4 and 5 should be quantified in prostate cancer. However, this has not been assessed in a cohort using prostate cancer death as an outcome, and there is debate as to whether the biopsy with the ‘worst’ percentage of HG disease or an ‘overall’ percentage of HG disease should be reported. Such data may assist in active surveillance decisions.Methods and resultsMen with clinically localised prostate cancer diagnosed by needle biopsy from 1990 to 2003 were included. The endpoint was prostate cancer death. Clinical variables included Gleason score (GS), prostate‐specific antigen level, age, clinical stage, and disease extent. Deaths were divided into those from prostate cancer and those from other causes, according to World Health Organization criteria. Nine hundred and eighty‐eight biopsy cases were centrally reviewed according to criteria agreed at the Chicago International Society of Urological Pathology conference in 2014. Cores were given individual GSs and Grade Groups (GGs), and a percentage of each grade was given for each core. Both the worst percentage of HG disease seen in a biopsy series and overall percentage of HG disease were calculated. The overall percentage of HG disease was highly significant, with a hazard ratio of 4.45 for the interquartile range (95% confidence interval 3.30–6.01, P < 2.2 × 10−16), and was similar to the percentage of HG disease seen in the worst core. In multivariate analysis, both were highly significant. GG2 cases with ≤5% Gleason pattern 4 showed similar survival to GG1 cases.ConclusionsThese data validate the use of percentage of HG disease to predict prostate cancer death. As both worst and overall percentage of HG disease are powerful predictors of outcome, either could be chosen to provide prognostic information.

The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study

BackgroundThe purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer.MethodsWe applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality.ResultsThe PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n = 20,586), C-index 0.77 vs. 074; radiotherapy (n = 11,872), C-index 0.73 vs. 0.69; and conservative management (n = 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001).ConclusionsThis validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

778P - Combined Analysis of an Rna Cell Cycle Progression (Ccp) Score for Predicting Prostate Cancer Death in Two Conservatively Managed Needle Biopsy Cohorts

ABSTRACT Aim: The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. Methods: We evaluate the predictive value of a cell cycle progression (CCP) score and a pre-specified linear combination of this score with standard clinical variables (CAPRA) as a combined clinical risk (CCR) score, for predicting prostate cancer death in two retrospective cohorts of conservatively managed patients diagnosed by needle biopsy. The first cohort consisted of 180 men diagnosed between 1990-96 and the second consisted of 585 men diagnosed mostly from 1997-2003 giving a combined cohort of 765 men. The primary endpoint was prostate cancer death within 10 years of diagnosis. Clinical variables consisted of centrally reviewed Gleason score, baseline PSA, age, clinical stage, and extent of disease; these were combined into a single predefined risk assessment (CAPRA) score. Results: In univariate analyses, the hazard ratio (HR) for a one unit change in CCP was 2.05 (95% CI(1.76, 2.46), k2 = 78.7, P Conclusions: The CCP score provides substantially more pre-treatment prognostic information than available from clinical variables and is useful for determining which patients can be safely managed by a conservative policy avoiding radical prostatectomy. In particular the combined score would have upgraded 18 patients with CAPRA ≤ 2 to have a higher risk, and downgraded 53 patients with CAPRA > 2 to have a low risk. Disclosure: J. Cuzick: Prof Cuzick has been a member of speaker's buro for Myriad Genetics and his Institution received reserach funding from Myriad Genetics; S. Stone: Employee of Myriad genetics; G. Fisher, B.V. North, D. Berney and L. Beltran: Working for an Institution that has received research funding from Myriad Genetics J.E. Reid and A. Gutin: Employee of Myriad Genetics;; J.S. Lanchbury and M. Brawer: Employed by Myriad genetics. All other authors have declared no conflicts of interest.

Validation of an RNA cell cycle progression (CCP) score for predicting prostate cancer death in a conservatively managed needle biopsy cohort.

5059 Background: The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. To val...

Validating the Interval to Biochemical Failure for the Identification of Potentially Lethal Prostate Cancer

Prostate specific antigen (PSA) is the earliest evidence of recurrent prostate cancer and defines biochemical failure (BF). However, BF alone does not indicate which patients are at risk of death from prostate cancer. The time interval to BF (IBF) has been shown to predict for prostate cancer mortality. We aimed to validate the role of IBF in predicting prostate cancer death in a multicenter dataset.

Reasons for initial PSA (iPSA) and biochemical failure (BF) being poor predictors of prostate cancer (PC) mortality

5153 Background: iPSA and BF are often poor predictors of mortality in men treated for locally advanced PC. We sought to find out why from prospective randomised trial data. Methods: In the TROG 96.01 trial men with T2b,c, 3, 4 N0 PC were randomised to 0, 3 or 6 months maximal androgen deprivation (AD) (goserelin 3.6 mg sc monthly and flutamide 250 mg po tid) prior to 66 Gy to the prostate and seminal vesicles. Failure site was diagnosed prior to salvage hormone therapy (ST) where possible, and type, timing and duration of response to ST recorded. Proportional hazards modeling was used to identify predictors of cause specific and overall survival (CSS, OS) at follow-up landmark points (where p&gt;0.05=NS, &lt;0.01=S, &lt;0.001=H). Results: Between 1996 and 2000, 802 eligible men were randomised. Higher iPSA was found to be a potent predictor of BF (Houston [HF])H but a poor one for of CSSNS and OSNS. Patients having HF and/or clinical failure had unfavourable initial prognostic factors (high iPSAH, stageH, Gleason scoreH or risk groupH) compared to patients who did not fail. However in this cohort poor initial prognostic features did not predict PC death when the relapse characteristics (failure siteH and PSA doubling timeH [PSA DT]) were accounted for. Instead lower iPSA levels were predictive of worse outcome in these modelsS, a finding supported by univariate analyses. PSA DT was found to correlate positively with interval between HF and STH and the likelihoodS and duration of response to STH, and survivalH. Thus lower PSA DTs were associated with earlier intervention but poorer responses and outcomes. Conclusions: Prognosis after BF is related more to tumour biology at relapse than to initial prognostic factors. ST alone is an unsatisfactory treatment for rapid PSA DT relapses. No significant financial relationships to disclose.

How Well Does the Gleason Score Predict Prostate Cancer Death? A 20-Year Followup of a Population Based Cohort in Sweden

Adenocarcinoma of the prostate is the most common cancer among men in Western countries. Although the prognostic heterogeneity of prostate cancer is enormous, clinically insignificant aggressive prostate cancers cannot be reliably distinguished. Therefore, identifying prognostic factors is increasingly important, notably among men diagnosed with localized prostate cancer, because many of them may not require aggressive treatment. We analyzed a population based cohort of 253 men with early stage (T1a-b, Nx, M0) initially untreated prostate cancer diagnosed between 1977 and 1991, before PSA screening was available. Tissue samples were available for 240 patients diagnosed with transurethral resection. During complete followup through September 2003, standardized criteria were used to classify histopathological characteristics, progression and causes of death. Higher Gleason grade, higher nuclear grade and larger tumor volume were independent predictors of death in prostate cancer with monotonous and statistically significant trends (p <0.05). In contrast, the level of Ki-67 - strongly correlated to Gleason score - was not an independent predictor of prostate cancer death. Given a Gleason score of 7 or greater, the probability of dying of prostate cancer was 29%. The corresponding predictive value for Gleason score 8 or greater was 48%. Although a high Gleason score is a determinant of prostate cancer death, its PPV is relatively low. Thus, further efforts in finding other or complementary indicators of prostate cancer outcome are needed.

Percent Gleason Grade 4/5 as Prognostic Factor in Prostate Cancer Diagnosed at Transurethral Resection

We investigated the value of percent Gleason grade 4/5 as a predictor of long-term outcome in men with prostate cancer diagnosed at transurethral resection who received deferred treatment. A series of 305 men with prostate cancer diagnosed at transurethral resection from 1975 to 1990 who had subsequent expectancy was analyzed. Mean patient age at diagnosis was 74 years (range 52 to 95). Slides were reviewed, and the Gleason score, percent Gleason grade 4/5 and modified Gleason score (the sum of the dominant and worst grades) were assessed. At followup 271 men (89%) had died, including 110 (36%) of prostate cancer. Gleason score, percent Gleason grade 4/5 and modified Gleason score were significant predictors of disease specific survival (p <0.001). Of all men 34% had tumors without any grade 4/5 pattern, of whom only 8% died of prostate cancer compared with 52% with any grade 4/5 pattern (p <0.001). Gleason score 6 tumors with focal grade 4 (less than 5%) had a worse prognosis than pure Gleason score 3 + 3 = 6 tumors (p = 0.008). There was nonsignificantly shorter survival for Gleason score 4 + 3 = 7 than for Gleason score 3 + 4 = 7 disease (p = 0.19). In Cox models including all possible pairs of Gleason score, percent Gleason grade 4/5 and modified Gleason score the percent Gleason grade 4/5 and modified Gleason score were stronger than Gleason score, although all 3 were independently significant prognosticators. Percent Gleason grade 4/5, modified Gleason score and Gleason score are predictors of disease specific survival in patients with prostate cancer on deferred treatment. Our study indicates that any grade 4/5 pattern impairs the prognosis significantly.