De Novo Metastatic Prostate Cancer Research Articles

Trends in local therapy utilization and survival of patients with de-novo metastatic prostate cancer treated by hormone therapy with or without systemic therapy intensification with chemotherapy.

90 Background: Guideline-recommended treatment for de novo metastatic prostate cancer (mPCa) includes hormone therapy (HT) and androgen receptor axis-targeted (ARAT) therapy with or without chemotherapy. While retrospective data have implicated the potential survival benefit of treating the primary tumor with radical prostatectomy, prospective clinical trials have demonstrated a benefit of definitive local radiotherapy in the context of low-volume mPCa. Given this emerging data, we sought to assess population-based treatment trends in the utilization of local therapy (LT) for mPCa and the association between the receipt of contemporary LT and overall survival in patients with mPCa. Methods: Using the National Cancer Database from 2004 to 2020, we identified men aged 18-90+ who were diagnosed with de-novo mPCa. To mitigate potential confounding, propensity score matching (PSM) was employed to balance patient characteristics between the two groups, including metastatic volume. High-volume mPCa was defined as the presence of any visceral metastases or bone metastases with at least 1 distant invasion. Cox proportional hazard models with clustering were utilized to estimate hazard ratios (HRs) for the risk of all-cause mortality to account for the inherent correlation created by PSM. Results: Among 30,713 patients, 2,569 (8.36%) received both LT and systemic therapy, while 26,038 (84.78%) received systemic therapy alone. Of these, 5,453 (19.06%) had high-volume PCa, and 23,154 (80.94%) had low-volume PCa. No upward trend in LT utilization was observed from 2004 to 2020, with fluctuations in rates observed over time. After PSM, LT was associated with lower all-cause mortality risk (HR=0.87, 95% CI: 0.81-0.93, p<0.001). In patients without chemotherapy intensification, LT was correlated with an 18% lower all-cause mortality risk (HR=0.82, 95% CI: 0.26-0.70, p<0.001), specifically, radical prostatectomy with a 72% lower risk (HR=0.28, 95% CI: 0.20-0.38, p<0.001). For patients receiving chemotherapy intensification, definitive radiotherapy was related to an 18% increased all-cause mortality risk (HR=1.18, 95% CI: 1.01-1.39, p=0.04), while radical prostatectomy showed a 54% decreased risk (HR=0.46, 95% CI: 0.29-0.74, p=0.001). Conclusions: We did not observe an increasing population-based utilization of LT. This contemporary analysis showed that LT was associated with a 13% reduction in the risk of all-cause mortality. Importantly, this observation was also seen in patients receiving systemic therapy intensification with chemotherapy. The retrospective nature of this data, as well as residual confounding despite PSM (including metastatic volume), remain important limitations in this study. Ongoing Phase 3 trials (S1802) will be critical for informing future widespread uptake of LT in mPCa.

Association between Statin Use and Clinical Outcomes in Patients with De Novo Metastatic Prostate Cancer: A Propensity Score-weighted Analysis.

Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer. We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors. The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p<0.001) compared to non-users. The median time to the development of castration-resistant status was similar between statin users and non-users (p=0.069). Multivariable Cox proportional hazards regression analysis, after IPTW adjustment, demonstrated that statin use was associated with improved overall survival. Our study indicates that the use of statins following a de novo metastatic prostate cancer diagnosis enhances survival outcomes. However, statins did not appear to delay the onset of castration-resistant status. Further large-scale and long-term studies are warranted to investigate the biological effects of statins in men with prostate cancer.

De Novo Metastatic Prostate Cancer: Are We Moving toward a Personalized Treatment?

De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5-10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since 2015, the prognosis of mHSPC has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. This review describes the current therapeutic opportunities for de novo mHSPC, focusing on potential molecular biomarkers identified in the main clinical trials that have modified the standard of care, the genomic features of de novo mHSPC, and the principal ongoing trials that are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment in this setting. The road toward personalized treatment for de novo mHSPC is still long, considering that the randomized clinical trials, which have furnished the basis of the current therapeutic options, stratified patients according to clinical criteria that did not necessarily reflect the biological rationale of the chosen therapy. The role of transcriptomic profiling of mHSPC as a predictive biomarker requires further validation, and it remains to be ascertained how the genomic variants detected in mHSPC, which are regarded as predictive in the castration-resistant disease, can be exploited in the mHSPC setting.

Survival Trend in Individuals With De Novo Metastatic Prostate Cancer After the Introduction of Doublet Therapy

Recently, life-prolonging treatments for patients with advanced prostate cancer have been introduced in clinical practice. To investigate if the introduction of doublet therapy is associated with changes in survival on a population-basis. This nationwide population-based cohort study used data from the Prostate Cancer data Base Sweden from 2008 to 2020. Men registered with de novo metastatic castration-sensitive prostate cancer (mCSPC) were included. The proportion of men with mCSPC who received doublet therapy, ie, androgen deprivation therapy plus androgen receptor pathway inhibitor drugs or chemotherapy was assessed. Standardized overall survival, taking age, comorbidity, and cancer characteristics into consideration, was estimated by use of a parametric survival model. A total of 11 382 men were included in this study (median [IQR] age, 74.0 [68-81] years). There was a shift toward less advanced prostate cancer during the study period with a decrease in median (IQR) prostate-specific antigen at diagnosis in men with mCSPC from 145 (39-571) ng/mL to 107 (27-426) ng/mL. Upfront treatment with doublet therapy in these men simultaneously increased from 1% (7 of 991) in 2016 to 44% (402 of 922) in 2020. The adjusted 5-year overall survival increased from 26% (95% CI, 25%-28%) from 2008 to 2012 to 35% (95% CI, 31%-40%) from 2017 to 2020. During the first 5 years after diagnosis, there was an increase in mean survival of 6 months, from 2.7 (95% CI, 2.6-2.8) years from 2008 to 2012 to 3.2 (95% CI, 3.1-3.1) years from 2017 to 2020. In parallel with improvements in treatment of advanced prostate cancer, a clinically meaningful increase in mean survival was observed in men with de novo mCSPC in Sweden between 2008 and 2020 in this study.

Effect of Concomitant Medications on Treatment Response and Survival in De Novo Metastatic Prostate Cancer: Secondary Analysis of the LATITUDE Study

It is unclear whether exposure to commonly prescribed medications influences survival and treatment response in patients with de novo high-risk metastatic prostate cancer (mPCa) treated with androgen receptor pathway inhibitors (ARPIs). We performed a secondary analysis of the LATITUDE trial to determine whether receipt of concomitant medications influenced the effect of abiraterone acetate and prednisone, in addition to androgen deprivation therapy (ADT), on overall survival (OS) and prostate cancer-specific mortality (PCSM) in patients with de novo mPCa. We focused on 7 commonly prescribed classes of medications: metformin, statins, proton pump inhibitors (PPIs), cyclooxygenase 2 (COX-2) inhibitors, aspirin, acetaminophen, and NSAIDs (nonselective COX inhibitors). To account for multiple testing, a two-sided p < 0.0024 was set as the threshold for statistical significance. Overall, 1135 patients were eligible. There was some evidence of a differential treatment effect from abiraterone among patients who received concomitant NSAIDs (hazard ratio [HR] for OS: 0.54; 95% CI: 0.42-0.70) versus those who did not (HR: 0.74; 95% CI: 0.60-0.91), though this did not reach significance (interaction p = 0.05). A similar non-significant finding of heterogeneity of effect from abiraterone was noted among patients who received concomitant aspirin (HR for OS: 0.93 [0.63-1.36]) versus those who did not (HR: 0.61 [0.51-0.73]) (interaction p = 0.04). Receipt of NSAIDs was independently associated with a significantly inferior OS (HR: 1.37 [1.15-1.62]; p < 0.001) and higher relative incidence of PCSM (sHR: 1.47 [1.21-1.78]; p < 0.001). This exploratory analysis did not find statistically significant evidence of differences in treatment effects from ADT plus abiraterone in de novo high-risk mPCa based on the receipt of concurrent medications. The receipt of NSAIDs was independently associated with increased PCSM and inferior OS.

Impact of Asian Race on Prognosis in De Novo Metastatic Prostate Cancer.

Little is known about the impact of Asian race on the long-term survival outcomes of males with de novo metastatic prostate cancer (PCa). Understanding racial disparities in survival is critical for accurate prognostic risk stratification and for informing the design of multiregional clinical trials. This multiple-cohort study included individual patient-level data for males with de novo metastatic PCa from the following 3 cohorts: LATITUDE clinical trial data (n=1,199), the SEER program (n=15,476), and the National Cancer Database (NCDB; n=10,366). Primary outcomes were overall survival (OS) in LATITUDE and NCDB and OS and cancer-specific survival in SEER. Across all 3 cohorts, Asian patients diagnosed with de novo metastatic PCa had better survival than white patients. In LATITUDE, median OS was significantly longer in Asian versus white patients in the androgen deprivation therapy (ADT) + abiraterone + prednisone group (not reached vs 43.8 months; hazard ratio [HR], 0.45; 95% CI, 0.28-0.73; P=.001) as well as in the ADT + placebo group (57.6 vs 32.7 months; HR, 0.51; 95% CI, 0.33-0.78; P=.002). In SEER, among all patients diagnosed with de novo metastatic PCa, median OS was significantly longer in Asian versus white males (49 vs 39 months; HR, 0.76; 95% CI, 0.68-0.84; P<.001). Among those who received chemotherapy, Asian patients again had longer OS (52 vs 42 months; HR, 0.71; 95% CI, 0.52-0.96; P=.025). Using data on cancer-specific survival in SEER resulted in similar conclusions. In NCDB, Asian patients also had longer OS than white patients in aggregate and in subgroups of males treated with ADT or chemotherapy (aggregate: 38 vs 26 months; HR, 0.72; 95% CI, 0.62-0.83; P<.001; ADT subgroup: 41 vs 26 months; HR, 0.71; 95% CI, 0.60-0.84; P<.001; chemotherapy subgroup: 34 vs 25 months; HR, 0.67; 95% CI, 0.57-0.78; P<.001). Asian males have better OS and cancer-specific survival than white males with metastatic PCa across different treatment regimens. This should be considered when assessing prognosis and in designing multinational clinical trials.

Local Therapeutics for the Treatment of Oligo Metastatic Prostate Cancer.

Metastatic prostate cancer remains universally lethal. Although de-novo metastatic prostate cancer was historically managed with systemic therapy alone, local therapies are increasingly utilized in the early treatment of the disease, particularly in patients with oligometastatic prostate cancer (OMPC). OMPC represents an intermediate stage between clinically localized and widespread metastatic disease. Diseases classified within this stage present an opportunity for localized targeting of the disease prior to progression to widespread metastases. The purpose of this review is to discuss the contemporary and emerging local therapies for the treatment of OMPC. To date, there are three utilized forms of local therapy for OMPC: cryoablation, radiation therapy, and cytoreductive prostatectomy. Cryoablation can be utilized for the total ablation of the prostate and has shown promising results in patients with OMPC either in combination with ADT or with ADT and systemic chemotherapy. Radiation therapy along with ADT has demonstrated improvement in progression-free survival. The STAMPEDE Arm G, PEACE-1, and the HORRAD clinical trials have investigated radiation therapy for mPCa compared to standard of care versus systemic therapy with varying results. Cytoreductive radical prostatectomy (CRP) in conjunction with ADT has also been proposed in the management of OPMC with promising results from case-control and retrospective studies. Currently there are larger controlled trials investigating CRP for OPMC including the SIMCAP, LoMP, TRoMbone, SWOG 1802, IP2-ATLANTA, g-RAMPP, and FUSCC-OMPCa trials. Given the novel nature of local treatments for OPMC, treatment selection is still controversial and requires long-term follow-up and randomized clinical trials to aid patient and clinician decision making.

Local Prostate Radiation Therapy and Symptomatic Local Events in De Novo Metastatic Prostate Cancer

PurposeLocal prostate radiation therapy (LPRT) for low-burden metastatic prostate cancer (mPCa) improves overall survival and is the standard of care. The role of LPRT in reducing symptomatic local events (SLE) remains unclear. We aimed to identify SLE risk factors and to evaluate the association between LPRT and SLE in mPCa. Methods and MaterialsWe conducted a retrospective, population-based cohort study of patients initially diagnosed with mPCa between 2005 and 2016 in a cancer registry. Patient, tumor, and treatment characteristics were obtained from chart review and the cancer registry. The coprimary endpoints were genitourinary (GU) and gastrointestinal (GI) SLE, identified by physician billing claims between 2004 and 2017 for diagnostic or therapeutic procedures potentially related to GU and GI SLE. The effect of LPRT on SLE was evaluated using both recurrent event (Andersen-Gill model) and time-to-first-event sequential landmark analyses. Risk factors for SLE were assessed by multivariable Cox regression. LPRT was defined as ≥40 Gy within 1 year of diagnosis. Metastatic burden was defined per the STAMPEDE trial. ResultsOf 1363 patients, 46 (3.4%) received LPRT. Median follow-up was 27.3 and 28.9 months in the control and LPRT groups, respectively. LPRT was associated with less recurrent GU SLE (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.17-0.67; P = .002), upper tract obstruction (HR, 0.20; 95% CI, 0.05-0.84; P = .03), and cystoscopy (HR, 0.38; 95% CI, 0.15-0.96; P = .04). Metastatic burden was not associated with SLE. ConclusionsLPRT in mPCa was associated with less recurrent GU SLE, specifically for upper tract obstruction and cystoscopy.

PD13-09 TRENDS IN SURVIVAL FOR MEN WITH DE NOVO METASTATIC PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022PD13-09 TRENDS IN SURVIVAL FOR MEN WITH DE NOVO METASTATIC PROSTATE CANCER Nina Wyatt, and Christopher Filson Nina WyattNina Wyatt More articles by this author , and Christopher FilsonChristopher Filson More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002545.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The USPSTF recommended against routine prostate cancer screening in 2008 (men >75 years) and 2011 (all men). After 2010, novel therapies were approved for men with metastatic prostate cancer, such as abiraterone. We examined the characteristics and survival of the men presenting with metastatic prostate cancer before and after those time periods. We hypothesized that men diagnosed more recently would have improved survival compared to men diagnosed long ago. METHODS: Using SEER cancer registry data, we identified men newly diagnosed with metastatic prostate cancer diagnosis from 2004–2018. Our outcome of interest was prostate cancer specific survival. Primary exposure was time period of diagnosis (2004–2008; 2009–2012; 2013–2016; 2017–2018). We evaluated factors including age, race/ethnicity, registry, and PSA level. We performed survival analysis to generate Kaplan-Meier curves for men eligible for at least 3 years follow up (diagnosed 2004–2016) (Figure). Multivariable Cox proportional hazard model provided adjusted estimates for cancer specific survival. RESULTS: Among 840,852 prostate cancer patients, 47,343 (5.6%) had metastatic disease. This proportion increased from 4.2% in 2004–2008 to 8.1% in 2017–2018 (p <0.001). Over time, a greater proportion of men with metastatic prostate cancer were Asian/Hispanic (16.0% in 2004–2008 to 17.7% in 2017–2018, p <0.001). Survival after 1 year was most common for men diagnosed in 2017–2018 (81.3% vs 67.9% alive in 2004–2008, p <0.001). Median cancer-specific survival was longest for men diagnosed from 2013–2016 (36 vs 31 months for 2004–2008, p <0.001). After adjusting for other factors, men diagnosed in 2013–2016 had 15% improved survival compared to those diagnosed earlier (vs 2004-2008; adjusted HR 0.85, 95% CI 0.82–0.88). CONCLUSIONS: Men presenting with metastatic prostate cancer in more recent years are living longer. More work will need to evaluate the relative contribution to this finding from therapeutic successes with novel systemic therapies, stage migration with adoption of PET scans, and the impact of earlier cancer detection with screening. Source of Funding: ACS MRSG 18-1-CPHPS © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e254 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nina Wyatt More articles by this author Christopher Filson More articles by this author Expand All Advertisement PDF DownloadLoading ...

Real-World Use of Androgen-Deprivation Therapy: Intensification Among Older Canadian Men With de Novo Metastatic Prostate Cancer.

BackgroundDespite the wealth of evidence demonstrating the efficacy of treatment intensification beyond androgen-deprivation therapy (ADT) among patients with de novo metastatic castration-sensitive prostate cancer (mCSPC), little is known of its real-world use. This study examined the real-world uptake of ADT treatment intensification among older men in a large Canadian province.MethodsWe performed a retrospective population-based cohort study using province-wide linked administrative data in Ontario, Canada. Patients 66 years of age and older with de novo mCSPC were included and their treatment with conventional ADT-based regimens, ADT plus next-generation androgen receptor axis–targeted therapy, and ADT plus docetaxel were identified and stratified by time.ResultsFrom 2014 to 2019, 3556 patients were identified with de novo mCSPC. Most patients (n = 2794 [78.6%]) were treated with a conventional ADT regimen, whereas 399 (11.2%) patients received ADT intensification with docetaxel and 52 (1.5%) patients received abiraterone acetate plus prednisone. In a time-stratified analysis of ADT intensification before and after the pivotal AA+P trial (LATITUDE), AA+P uptake increased from 0.5% to 3.0%, whereas docetaxel use dropped from 12.0% to 10.0%. The median survival of the study population was 18 months (interquartile range = 10-31).ConclusionsThe majority of patients with de novo mCSPC are treated with ADT alone in the Canadian real-world setting, despite randomized clinical trial evidence of benefit with the use of ADT-intensified regimens. As ADT treatment intensification is substantially underused, better understanding of the barriers to treatment and targeted education to address them are needed.

Epidemiological Characteristics and Survival in Patients with De Novo Metastatic Prostate Cancer.

Simple SummaryIn randomized trials, both chemotherapy and androgen-receptor signaling inhibitors provided significant survival benefits in patients with metastatic prostate cancer (mPCa). However, it is largely unknown to what extent these therapeutic advances have impacted the general, real-world survival of patients with de novo mPCa. Here, we analyzed more than 26,000 patients included in the U.S. Surveillance, Epidemiology, and End Results (SEER) database to describe potential recent improvements in overall and cancer-specific survival. We found that patients diagnosed in the latest years showed a modest reduction in the risk of death and cancer-specific death, compared with those diagnosed in 2000–2003 and 2004–2010. Although our analysis was not adjusted for many confounders, the overall population of patients diagnosed in 2011–2014 only showed a survival gain of 4 months. Patients’ ineligibility or refusal of anticancer treatments, insurance issues, intrinsic disease aggressiveness, or prior unavailability of drugs in a hormone-sensitive setting might contribute to these disappointing results.The real-world outcomes of patients with metastatic prostate cancer (mPCa) are largely unexplored. We investigated the trends in overall survival (OS) and cancer-specific survival (CSS) in patients with de novo mPCa according to distinct time periods. The U.S. Surveillance, Epidemiology, and End Results (SEER) Research Data (2000–2017) were analyzed using the SEER*Stat software. The Kaplan–Meier method and Cox regression were used. Patients with de novo mPCa were allocated to three cohorts based on the year of diagnosis: A (2000–2003), B (2004–2010), and C (2011–2014). The maximum follow-up was fixed to 5 years. Overall, 26,434 patients were included. Age, race, and metastatic stage (M1) significantly affected OS and CSS. After adjustment for age and race, patients in Cohort C showed a 9% reduced risk of death (hazard ratio (HR): 0.91 (95% confidence interval [CI] 0.87–0.95), p < 0.001) and an 8% reduced risk of cancer-specific death (HR: 0.92 (95% CI 0.88–0.96), p < 0.001) compared with those in Cohort A. After adjustment for age, race, and metastatic stage, patients in Cohort C showed an improvement in OS and CSS compared with Cohort B (HR: 0.94 (95% CI 0.91–0.97), p = 0.001; HR: 0.89 (95% CI 0.85–0.92), p < 0.001). Patients with M1c disease had a more pronounced improvement in OS and CSS compared with the other stages. No differences were found between Cohorts B and C. In conclusion, the real-world survival of de novo mPCa remains poor, with a median OS and CSS improvement of only 4 months in the latest years.

Implications of the United States Preventive Services Task Force Recommendations on Prostate Cancer Stage Migration.

Prostate-specific antigen screening is controversial. In 2008, the United States Preventive Services Task Force recommended against screening men aged≥ 75 years, and in 2012, expanded this to include all men. The impact of these changes continues to unfold. We hypothesized that these screening changes could delay the diagnosis of advanced prostate cancer. The Surveillance, Epidemiology, and End Results database was used to identify men (age, 55-69 years) diagnosed with prostate cancer in 2004 to 2008 (group 1), 2009 to 2012 (group 2), and 2013 to 2015 (group 3). Groups reflect United States Preventive Services Task Force guideline changes. Descriptive statistics were used to present baseline statistics and the number of patients diagnosed in aforementioned groups. Data was adjusted for population growth. A total of 328,586 men were identified (group 1, 135,625; group 2, 117,979; group 3, 74,982). The average number of men diagnosed annually with N1M0 (group 1, 381; group 2, 477; group 3, 660) and M1 (group 1, 523; group 2, 761; group 3, 1037) disease increased. With group 1 as control, there was a decrease in the incidence of localized disease (group 2, 9.2%; group 3, 33.2%). However, the incidence of N1M0 (group 2, 5.3%; group 3, 30.1%) and M1 disease (group 2, 22.6%; group 3, 49.2%) increased. Separate analyses of patients (age 50-75 years) and African Americans showed similar trends. With each recommendation, there was increased incidence of de novo metastatic prostate cancer. The sequelae of advanced disease include financial, emotional, and physical burden. Future studies are needed to identify screening strategies that reduce the risk of developing metastatic disease without over-diagnosing indolent cancers.

HLA Class I Allele Expression and Clinical Outcome in De Novo Metastatic Prostate Cancer.

The prognostic value of human leukocyte antigen (HLA) class I molecules in prostate cancer (PCa) remains unclear. Herein, we investigated the prognostic relevance of the most frequently expressed HLA-A alleles in Greece (A*02:01 and HLA-A*24:02) in de novo metastatic hormone-sensitive PCa (mPCa), which is a rare and aggressive disease characterized by a rapid progression to castration-resistance (CR) and poor overall survival (OS), contributing to almost 50% of PCa-related deaths. We identified 56 patients who had either progressed to CR (these patients were retrospectively analyzed for the time to the progression of CR and prospectively for OS) or had at least three months’ follow-up postdiagnosis without CR progression and, thus, were prospectively analyzed for both CR and OS. Patients expressing HLA-A*02:01 showed poor clinical outcomes vs. HLA-A*02:01−negative patients. HLA-A*24:02−positive patients progressed slower to CR and had increased OS. Homozygous HLA-A*02:01 patients progressed severely to CR, with very short OS. Multivariate analyses ascribed to both HLA alleles significant prognostic values for the time to progression (TTP) to CR and OS. The presence of HLA-A*02:01 and HLA-A*24:02 alleles in de novo mPCa patients are significantly and independently associated with unfavorable or favorable clinical outcomes, respectively, suggesting their possible prognostic relevance for treatment decision-making in the context of precision medicine.

Serum Prognostic Factors of Androgen-deprivation Therapy Among Japanese Men With De Novo Metastatic Prostate Cancer.

To date, several serum prognostic factors have been reported in metastatic prostate cancer. In this study, we examined the prognostic value of these serum markers in Japanese men. This study included 104 patients with metastatic prostate cancer who were treated with primary androgen-deprivation therapy from 2001 to 2013. Clinicopathological factors including several serum markers were investigated for association with progression-free (PFS) and overall (OS) survival. During a median follow-up of 48.1 months, median PFS and OS were 24.0 months and 67.4 months, respectively. When adjusted by age, prostate-specific antigen at diagnosis, Gleason score, and clinical stage, serum lactate dehydrogenase value was significantly associated with PFS [hazard ratio (HR)=1.42, 95% confidence interval (CI)=1.15-1.74; p=0.0004] and OS (HR=1.46, 95% CI=1.13-1.82; p=0.0014), in addition to alkaline phosphatase value for OS (HR=1.04; 95% CI=1.00-1.07; p=0.015). This study demonstrates the prognostic significance of alkaline phosphatase and lactate dehydrogenase values in Japanese men with de novo metastatic hormone-sensitive prostate cancer.

Impact of the USPSTF recommendations on prostate cancer stage migration and de-novo metastatic prostate cancer.

166 Background: The US Preventive Services Task Force (USPSTF) recommended against prostate specific antigen (PSA) screening for men aged≥75 in 2008 and all men in 2012 in an effort to reduce overdiagnosis and overtreatment of men with prostate cancer (PCa). This recommendation may delay diagnosis of clinically significant PCa. Methods: The Surveillance, Epidemiology and End Results Program (SEER) was used to identify men diagnosed with PCa between 2004-2015. PCa stage was categorized as localized (N0M0), nodal (N1M0) and metastatic (NxM1). Trend analysis was stratified on age group (PSA screening eligible was defined as age 55-69 according to the 2018 updated USPSTF recommendation). Multivariable logistic regression was used to identify predictors for nodal and metastatic disease. Results: Between 2004-2015, there were 603,323 men with PCa identified. Metastatic disease accounted for 2.8% of PCa in 2004-2008, 3.7% in 2009-2012, and 6.1% in 2013-2015. In men eligible for PCa screening, metastatic disease increased from 1.9% in 2004-2008, to 2.6% in 2009-2012, to 4.2% in 2013-2015; nodal disease increased from 1.4% to 1.6% to 2.6%, respectively (both p-value for trend&lt; 0.0001). This stage migration was also observed in non-screening eligible groups (age &gt;70 and &lt;55). Compared with PCa diagnosed in 2009-2012, PCa diagnosed in 2013-2015 had higher odds of metastatic disease (AOR: 1.70, p-value&lt;0.0001) or nodal disease (AOR: 1.71, p-value&lt;0.0001). Conclusions: Men diagnosed with PCa in 2013-2015 were more likely to have metastatic or nodal disease, suggesting PCa stage migration since PSA screening was recommended to be discontinued in 2012. Although the impact of PSA screening on PCa mortality remains debatable, the reduced quality of life with advanced Pca should not be overlooked. Future population studies are warranted to investigate the influence of the updated 2018 USPSTF recommendation. [Table: see text]

Circulating Tumor DNA Abundance and Potential Utility in De Novo Metastatic Prostate Cancer

BackgroundSeveral systemic therapeutic options exist for metastatic castrate-sensitive prostate cancer (mCSPC). Circulating tumor DNA (ctDNA) can molecularly profile metastatic castration-resistant prostate cancer and can influence decision-making, but remains untested in mCSPC. ObjectiveTo determine ctDNA abundance at de novo mCSPC diagnosis and whether ctDNA provides complementary clinically relevant information to a prostate biopsy. Design, setting, and participantsWe collected plasma cell-free DNA (cfDNA) from 53 patients newly diagnosed with mCSPC and, where possible, during treatment. Targeted sequencing was performed on cfDNA and DNA from diagnostic prostate tissue. Results and limitationsThe median ctDNA fraction was 11% (range 0–84%) among untreated patients but was lower (1.0%, range 0-51%) among patients after short-term (median 22d) androgen deprivation therapy (ADT). TP53 mutations and DNA repair defects were identified in 47% and 21% of the cohort, respectively. The concordance for mutation detection in matched samples was 80%. Combined ctDNA and tissue analysis identified potential driver alterations in 94% of patients, whereas ctDNA or prostate biopsy alone was insufficient in 19 cases (36%). Limitations include the use of a narrow gene panel and undersampling of primary disease by prostate biopsy. ConclusionsctDNA provides additional information to a prostate biopsy in men with de novo mCSPC, but ADT rapidly reduces ctDNA availability. Primary tissue and ctDNA share relevant somatic alterations, suggesting that either is suitable for molecular subtyping in de novo mCSPC. The optimal approach for biomarker development should utilize both a tissue and liquid biopsy at diagnosis, as neither captures clinically relevant somatic alterations in all patients. Patient summaryIn men with advanced prostate cancer, tumor DNA shed into the bloodstream can be measured via a blood test. The information from this test provides complementary information to a prostate needle biopsy and could be used to guide management strategies.Sequencing data were deposited in the European Genome-phenome Archive (EGA) under study identifier EGAS00001003351.

Incidence and survival trends of de-novo metastatic prostate cancer - a population-based analysis of two national cohorts from USA and Denmark

Incidence and survival trends of de-novo metastatic prostate cancer - a population-based analysis of two national cohorts from USA and Denmark

Effect on Overall Survival of Locoregional Treatment in a Cohort of De Novo Metastatic Prostate Cancer Patients: A Single Institution Retrospective Analysis From the Royal Marsden Hospital.

The optimal management of the primary tumor in metastatic at diagnosis (M1) prostate cancer (PCa) patients is not yet established. We retrospectively evaluated the effect of locoregional treatment (LRT) on overall survival (OS) hypothesizing that this could improve outcome through better local disease control and the induction of an antitumor immune response (abscopal effect). M1 at diagnosis PCa patients referred to the Prostate Targeted Therapy Group at the Royal Marsden between June 2003 and December 2013 were identified. LRT was defined as either surgery, radiotherapy (RT) or transurethral prostatectomy (TURP) administered to the primary tumor at any time point from diagnosis to death. Kaplan-Meier analyses generated OS data. The association between LRT and OS was evaluated in univariate (UV) and multivariate (MV) Cox regression models. Overall 300 patients were identified; 192 patients (64%) experienced local symptoms at some point during their disease course; 72 patients received LRT (56.9% TURP, 52.7% RT). None of the patients were treated with prostatectomy. LRT was more frequently performed in patients with low volume disease (35.4% vs. 16.2%; P< .001), lower prostate-specific antigen (PSA) level at diagnosis (median PSA: 75 vs. 184 ng/mL; P= .005) and local symptoms (34.2% vs. 4.8%; P< .001). LRT was associated in UV and MV analysis with longer OS (62.1 vs. 55.8 months; hazard ratio [HR], 0.74; P= .044), which remained significant for RT (69.4 vs. 55.1 months; HR, 0.54; P= .002) but not for TURP. RT was associated with better OS independent of disease volume at diagnosis. These data support the conduct of randomized phase III trials to evaluate the benefit of local control in patients with M1 disease at diagnosis.

De novo metastatic prostate cancer: Patterns of PSA testing prediagnosis and disease characteristics.

271 Background: A small proportion of men with prostate cancer (PCa) will present with metastatic disease at first presentation, termed de novo metastatic PCa. PSA screening is not a national policy, yet PSA testing is commonly performed and national guidelines are available to guide subsequent management. We sought to investigate this group of men to determine if prior PSA testing had been previously performed, and if elevated, to determine if appropriate referrals were being made. We also sought to further characterise and analyse associated risk factors. Methods: A retrospective review of pts who presented with de novometastatic PCa over a three year period was performed in three cancer centres in Ireland. Characteristics such as demographics, Gleason score, symptoms at presentation and disease volume (high v low) were obtained. PSA results done in the primary care for a period of 12-24 months and &gt; 24 months prior to diagnosis were recorded. Results: 100 pts with de novo metastatic PCa were identified between 2013 and 2015. Median age at diagnosis was 72 years (49-90), 77 pts (77%) presented with high volume disease, 11 pts (11%) had evidence of visceral metastasis with a median age of 62 years (51-72). Median PSA level at diagnosis was 106, and 91% of pts (n = 74) had a Gleason score of ≥ 8. Symptoms at presentation were evaluable in 88 pts with the majority of pts presenting with pain (n = 49, 55.6%) and lower urinary tract symptoms (n = 33, 37.5%). 22 pts (22%) had a PSA level done within 12-24 months prior to diagnosis which was higher than 4.0 ng/ml in 18 pts (82%). 57 pts (57%) had a PSA level done over 24 months prior to diagnosis which was higher than 4.0 ng/ml in 35 pts (61.4%), PSA measurement was only repeated in 18 pts (51%) out of 35 pts with high PSA levels prior to diagnosis. Having elevated PSA levels over 4.0 ng/ml within 12-24 months and over 24 months prior to diagnosis was not associated high volume metastatic disease (P = 0.88). Conclusions: A sizeable proportion of pts diagnosed with de novo metastatic PCa had PSA measurements performed more than one year prior to diagnosis which was elevated. Optimization and adherence to national guidelines regarding PSA testing is needed to decrease the number of pts diagnosed with de novo disease.

Characterization of patients who present with de novo metastatic prostate cancer: Single-institution database analysis.

33 Background: Less than 5% of men in a PSA screened population present with denovo metastatic prostate cancer. We sought to characterize the clinical characteristics and survival of this unique group of men. Methods: Retrospective analysis of an institutional data-base – Dana Farber Cancer Institute - Prostate Clinical Research Information Systems (CRIS). All men with metastatic disease as their first presentation of prostate cancer were identified. Patient and disease characteristics were summarized descriptively. The distributions of the study endpoints were estimated using the Kaplan-Meier method with median and 95%CI reported. Results: The analytic cohort has 185 patients with a median follow-up of 7.8 years (95% CI:7.5,11.1) and 94% diagnosed after 1998. Median age at diagnosis is 62 years (Range: 42-86); PSA at diagnosis: Median (Q1-Q3) - 100.2 (23.0, 346.0). Metastases: 97% bone, 2% liver, 2% lung, 8% lymph node. The median time from metastasis diagnosis to start of androgen deprivation therapy (ADT) was 26 days, 139 of those who started ADT had subsequently started treatment for castration resistant prostate cancer (CRPC) - 2nd line hormonal therapy and/or chemotherapy. The median time from ADT to subsequent therapy for CRPC is 14 months with 95% (CI:12,16). 128 patients have died and the median overall survival is 48 months (95% CI:40, 51). Conclusions: This unique cohort of patients at a referral institution tend to be younger and have an overall survival comparable to outcomes in modern day randomized hormone sensitive prostate cancer studies. Assessment of similar group in a multivariate analysis of a prospective trial is needed to confirm this observation. If confirmed, the data would suggest the responsiveness to therapy drives outcome rather than development of metastasis with or without a previously treated primary.