Worse Prostate Cancer-specific Survival Research Articles

Ten-year outcomes of whole-pelvic intensity-modulated radiation therapy for prostate cancer with regional lymph node metastasis.

Management of pelvic node-positive prostate cancer has been challenging and controversial. We conducted a study to evaluate the outcomes of whole-pelvic (WP) simultaneous integrated boost (SIB) intensity-modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT). A total of 67 consecutive patients with cT1c-4N1M0 prostate cancer were definitively treated by WP SIB-IMRT. Neoadjuvant ADT (median: 8.3months) was administered in all cases. WP SIB-IMRT was designed to simultaneously deliver 78, 66.3, and 58.5Gy in 39 fractions to the prostate plus seminal vesicles, metastatic lymph nodes (LNs), and the pelvic LN region, respectively. Adjuvant ADT (median: 24.7months) was administered in 66 patients. The median follow-up period was 81.6months (range: 30.5-160.7). Biochemical relapse-free, overall, and prostate cancer-specific survival rates at 10 years were 59.8%, 79.6%, and 86.3%, respectively. Loco-regional recurrence was not observed. Being in International Society of Urological Pathology grade group 5 and having a posttreatment detectable nadir prostate-specific antigen (PSA) level (≥0.010 ng/ml) were significantly associated with worse prostate cancer-specific survival and progression of castration resistance. The 10-year cumulative incidence rates of grade 2 and 3 late toxicities were, respectively, 1.5% and 0% for genitourinary, 0% and 1.5% for gastrointestinal events. No grade 4 acute or late toxicities were observed. WP SIB-IMRT can be safely administered to patients with pelvic node-positive prostate cancer. Since grade group 5 and detectable nadir PSA levels are risks for castration resistance, we may need to increase the intensity of treatment for such cases.

Changes in prostate cancer survival among insured patients in relation to USPSTF screening recommendations

BackgroundTo investigate the effects of the U.S. Preventive Services Task Force’s (USPSTF) 2012 recommendation against prostate-specific antigen (PSA)-based screening for prostate cancer on survival disparities based on insurance status. Prior to the USPSTF’s 2012 screening recommendation, previous studies found that insured patients with prostate cancer had better outcomes than uninsured patients.MethodsUsing the SEER 18 database, we examined prostate cancer-specific survival (PCSS) based on diagnostic time period and insurance status. Patients were designated as belonging to the pre-USPSTF era if diagnosed in 2010–2012 or post-USPSTF era if diagnosed in 2014–2016. PCSS was measured with the Kaplan–Meier method, while disparities were measured with the Cox proportional hazards model.ResultsDuring the pre-USPSTF era, uninsured patients experienced worse PCSS compared to insured patients (adjusted HR 1.256, 95% CI 1.037–1.520, p = 0.020). This survival disparity was no longer observed during the post-USPSTF era as a result of decreased PCSS among insured patients combined with unchanged PCSS among uninsured patients (adjusted HR 0.946, 95% CI 0.642–1.394, p = 0.780).ConclusionsAlthough the underlying reasons are not clear, the USPSTF’s 2012 PSA screening recommendation may have hindered insured patients from being regularly screened for prostate cancer and selectively led to worse outcomes for insured patients without affecting the survival of uninsured patients.

Access and Representation: A Narrative Review of the Disparities in Access to Clinical Trials and Precision Oncology in Black men with Prostate Cancer

To provide commentary on the disparities in access to clinical trials and precision oncology specific to Black men with Prostate Cancer (PCa) in the United States and lend a general framework to aid in closing these gaps. The ideas, commentaries and data presented in this narrative review were synthesized by utilizing qualitative and quantitative studies, reviews, and randomized control trials performed between 2010 and 2021. We searched PubMed using the key words "Medicaid", "Medicare", "clinical trials", "African Americans", "Black", "underrepresentation", "access", "Prostate Cancer", "minority recruitment", "racial disparities", "disparity", "genomics", "biomarkers", "diagnostic" "prognostic", "validation", "precision medicine", and "precision oncology" to identify important themes, trends and data described in the current review. Keywords were used alone and combination with both "AND" and "OR" terms. Black men with prostate cancer (PCa) in the United States have earlier onset of disease, present with more advanced stages, and worse prostate cancer-specific survival than their White counterparts. Potential causative factors vary from disparities in health care access to differences in tumor immunobiology and genomics along with disparate screening rates, management patterns and underrepresentation in clinical and translational research such as clinical trials and precision oncology. To avoid increasing the racial disparity in PCa outcomes for Black men, we must increase inclusion of Black men into precision oncology and clinical trials, using multilevel change. Underrepresentation in clinical and translational research may potentiate poorly validated risk calculators and biomarkers, leading to poor treatment decisions in high-risk populations. Relevant actions include funding to include minority-serving institutions as recruitment sites, and inclusion of evidence based recruitment methods in funded research to increase Black representation in clinical trials and translational research.

Rise in serum folate after androgen deprivation associated with worse prostate cancer-specific survival

IntroductionHigh folate has an association with advanced prostate cancer and levels of testosterone. Herein, we perform a translational study to investigate the inverse response of serum folate in prostate cancer patients initiating androgen deprivation therapy (ADT) and a mirrored animal model. MethodsA retrospective study was performed using the South Texas Veterans Healthcare System to identify patients with prostate cancer on ADT. We documented testosterone and folate levels before and after ADT initiation (defined by a reduction in testosterone by 50 ng/ml) as compared to those already on ADT (maintenance). Our primary outcome was overall mortality with secondary outcome of prostate cancer-specific mortality. In parallel, we tested castration of C57BL/6J mice on folate-defined diet to determine if folate levels change with response to androgen deprivation. Students’ t test on continuous variables and Chi-squared test on dichotomous variables was performed along with Kaplan-Meier for time to event analysis. ResultsWe identified 56 men with prostate cancer undergoing androgen deprivation in which folate levels had been determined. 15 out of 16 (94%) men initiating ADT had increases in their folate, which is substantially more than 67% in maintenance group (P = 0.04). We identified more rapid time to death from prostate cancer if folate levels increased to levels >200 ng/ml above their baseline (P = 0.03). Mice models demonstrated a significant rise in serum red blood cell folate after mice were castrated (P = 0.03) by an average of 1.5x over pre-castrated baseline level. By contrast, sham-castrated mice showed no increase in serum folate levels over baseline. ConclusionOur study suggests that men with substantial rises in folate after initiating ADT may be associated with worse prostate cancer-specific and overall survival. Our translational experiments in mice confirmed correlation between rising in folate levels post-castration. Given this study, further investigation is warranted on the role of dietary folate consumption during initiation of ADT and progression to castrate-resistant prostate cancer.

Comparing Radiotherapy Versus Surgery in Men with High-Risk Prostate Cancer: An Outcomes-based Analysis

We evaluated outcomes of men with clinically localized high-risk prostate cancer (HRPCa) definitively treated with combined external beam radiotherapy and androgen deprivation therapy (EBRT) versus radical prostatectomy (RP). Men diagnosed with HRPCa definitively treated with either EBRT or RP from 2008-2016 were included in this study. All clinical data were queried from our IRB-approved multi-institutional tumor registry confirming diagnosis of HRPCa as classified by initial prostate-specific antigen (iPSA), clinical T-stage (cT), and biopsy Gleason score (cGS). Survival outcomes, which included freedom from biochemical failure (FFBF), biochemical control (BC), prostate cancer-specific survival (PCSS), and overall survival (OS), were calculated from date of surgery or EBRT completion. BC differed from FFBF only for a subset of RP patients who were biochemically controlled with salvage radiotherapy (SRT). ANOVA and Chi-Square testing were used to identify differences in baseline characteristics between treatment cohorts. Log-rank testing was used to identify survival differences. Multivariate cox regression analysis (MVA) was used to identify clinical predictors of study outcomes. 1528 Men with a median age of 66 were included in this analysis. Median follow-up of EBRT (n=665) and RP (n=863) patients were 61 and 59 months, respectively. Rate of ADT use with EBRT was 86%. One third of RP patients received post-operative radiotherapy (PORT), with the majority receiving SRT. Comparison of baseline characteristics showed that EBRT patients presented with higher age, iPSA, cT, cGS, and percentage of positive biopsy cores (PPC) compared to RP patients. At seven years, EBRT patients had superior FFBF (50% v. 40%, p<0.001) and equivalent BC (50%) compared to RP patients. EBRT patients had worse OS (71% v. 88%, p<0.001). EBRT patients had worse PCSS at seven years (91% v. 95%), however this difference was not statistically significant (p=0.07). MVA demonstrated that higher iPSA, PPC, cT, cGS, and treatment with RP were associated with worse FFBF and BC. Higher age, PPC, and cGS were associated with worse PCSS. Higher age, PPC, cT, and treatment with EBRT were associated with worse OS. For EBRT patients, ADT use was associated with better FFBF. Hypofractionation was not associated with outcomes. For RP patients, choice of RP technique was not associated with outcomes. Despite having worse disease characteristics at baseline, men who received EBRT had superior FFBF, equivalent BC, and similar PCSS compared to men who underwent RP. A PORT rate of 33% suggests that additional therapy was necessary to achieve similar long-term oncologic outcomes in men treated with RP compared to EBRT. These findings highlight the utility of EBRT in the management of HRPCa.

Outcomes of Clinically High-Risk Prostate Cancer Patients Undergoing Radical Prostatectomy with or without Post-operative Radiation: A Multi-Institutional Analysis

We evaluated outcomes of men diagnosed with clinically localized high-risk prostate cancer (HRCaP) definitively managed with radical prostatectomy (RP) with or without adjuvant (ART) or salvage (SRT) post-operative radiation (PORT). Men diagnosed with HRCaP, who were definitively treated with RP with or without PORT from 2008-2016, were included in this study. All data were queried from our multi-institutional tumor registry. Freedom from biochemical failure (FFBF), biochemical control following PORT, prostate cancer-specific survival (PCSS), and overall survival (OS) were calculated from date of surgery. Multivariate cox regression analysis (MVA) was used to identify factors significantly (p<0.05) associated with study outcomes. 863 men were included in this study with a median follow-up of 60 months. 284 men were treated with PORT (ART= 55 men and SRT= 229 men). 7-year rates of FFBF, PCSS, and OS for men treated with RP were 40.3%, 95.0%, and 88.1%, respectively. On MVA, higher tumor volume, advanced pathologic tumor stage (T-stage), higher pathologic Gleason score (GS), and positive margins were associated with inferior FFBF in men undergoing RP. Advanced T-stage and positive margins were associated with worse PCSS. Advanced T-stage, higher GS, and persistent PSA, were associated with worse OS. At 7 years, ART was associated with superior biochemical control compared to SRT (43.0% vs 29.5%, p=0.004). No differences were seen between ART and SRT in terms of PCSS and OS. In men undergoing SRT, higher GS, persistent PSA, higher PSA at initiation of SRT, and lack of concurrent ADT were associated with worse biochemical control. Advanced T-stage and positive margins were associated with worse PCSS, and persistent PSA was associated with worse OS. Initiation of SRT with a PSA≤1 was associated with superior biochemical control compared to patients treated with SRT at a PSA>1. In our multi-institutional analysis, we observed that following RP for HRCaP, 1 in 3 men ultimately received PORT. ART, compared to SRT, was associated with superior biochemical control. In men treated with SRT, SRT was more effective when treatment was initiated at a lower post-operative PSA. We await the results of RADICALS and RAVES to better determine optimal timing and use of PORT with or without ADT in HRCaP patients who undergo RP.

Both High and Low Serum Total Testosterone Levels Indicate Poor Prognosis in Patients with Prostate Cancer.

Androgen-androgen receptor (AR) signal is known as a powerful driver of prostate cancer progression. We previously reported the limitation of prostate-specific antigen (PSA) at diagnosis as a prognostic biomarker of prostate cancer. Although serum total testosterone (TT) level has been reported as a prognostic biomarker for prostate cancer, its usability is still controversial. We examined the potential and characteristics of TT as a biomarker. Serum TT levels of patients who underwent prostate biopsy were measured, and prostate cancer-specific survival (PCaSS), overall survival (OS), and the correlation between staging and serum TT level were analyzed. Of 379 biopsied patients, 255 were diagnosed with prostate cancer. The patients were divided into five groups according to their serum TT levels; patients with serum TT levels of <2 or ≥8 ng/ml (ENDs) had worse PCaSS and OS compared with those with middle serum TT levels between 2 and 8 ng/ml (MIDs). Moreover, ENDs showed a tendency of having castration-resistant cancer with advanced stage (T4 or N1 or M1). The TNM stage in ENDs was significantly higher than in MIDs. Although low serum TT level has been reported to indicate worse outcome in patients with prostate cancer, this study showed that both low as well as high serum TT levels indicate poor prognosis.

Polymorphisms inside MicroRNAs and MicroRNA Target Sites Predict Clinical Outcomes in Prostate Cancer Patients Receiving Androgen-Deprivation Therapy

Recent evidence indicates that small noncoding RNA molecules, known as microRNAs (miRNAs), are involved in cancer initiation and progression. We hypothesized that genetic variations in miRNAs and miRNA target sites could be associated with the efficacy of androgen-deprivation therapy (ADT) in men with prostate cancer. We systematically evaluated 61 common single nucleotide polymorphisms (SNPs) inside miRNAs and miRNA target sites in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT were assessed by Kaplan-Meier analysis and Cox regression model. Four, seven, and four SNPs were significantly associated with disease progression, PCSM, and ACM, respectively, after ADT in univariate analysis. KIF3C rs6728684, CDON rs3737336, and IFI30 rs1045747 genotypes remained as significant predictors for disease progression; KIF3C rs6728684, PALLD rs1071738, GABRA1 rs998754, and SYT9 rs4351800 remained as significant predictors for PCSM; and SYT9 rs4351800 remained as a significant predictor for ACM in multivariate models that included clinicopathologic predictors. Moreover, strong combined genotype effects on disease progression and PCSM were also observed. Patients with a greater number of unfavorable genotypes had a shorter time to progression and worse prostate cancer-specific survival during ADT (P for trend < 0.001). SNPs inside miRNAs and miRNA target sites have a potential value to improve outcome prediction in prostate cancer patients receiving ADT.

2060 DOES PSA DOUBLING TIME AFTER RADICAL PROSTATECTOMY CORRELATE WITH OVERALL SURVIVAL? A REPORT FROM THE SEARCH DATABASE GROUP

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 20102060 DOES PSA DOUBLING TIME AFTER RADICAL PROSTATECTOMY CORRELATE WITH OVERALL SURVIVAL? A REPORT FROM THE SEARCH DATABASE GROUP Anna Teeter, William Aronson, Joseph Presti, Martha Terris, Christopher Amling, Christopher Kane, and Stephen Freedland Anna TeeterAnna Teeter Durham, NC More articles by this author , William AronsonWilliam Aronson Los Angeles, CA More articles by this author , Joseph PrestiJoseph Presti Palo Alto, CA More articles by this author , Martha TerrisMartha Terris Augusta, GA More articles by this author , Christopher AmlingChristopher Amling Portland, OR More articles by this author , Christopher KaneChristopher Kane San Diego, CA More articles by this author , and Stephen FreedlandStephen Freedland Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2107AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Others have shown that a short PSA doubling time (PSADT) following recurrence after radical prostatectomy (RP) portends a poor prognosis and poor response to salvage treatment. However, many of these observations have been made in populations of relatively young, racially homogenous men treated at tertiary care centers and only one study has previously examined the correlation between PSADT and overall survival (OS). We sought to examine the correlation between PSADT and OS as well as the correlation between PSADT and prostate cancer-specific survival among men in the SEARCH database, which is an older, racially diverse cohort of men treated with RP at multiple Veterans Affairs medical centers nationwide. METHODS We performed a Cox proportional hazards analysis to examine the correlation between post-recurrence PSADT and time from recurrence to OS as well as the correlation between post-recurrence PSADT and time from recurrence to prostate cancer-specific survival among 345 men in the SEARCH database who underwent RP between 1988 and 2008. RESULTS We examined PSADT as a categorical variable based on the clinically significant cut-points of <3, 3-8.9, 9-14.9, and ≥15 months. When this was done, a PSADT of <3 (HR 5.48, p=0.002) was associated with poorer OS relative to men with a PSADT ≥15 months. Additionally, there was a trend towards men with a PSADT of 3-8.9 months (HR 1.70, p=0.07) having worse OS. A PSADT of 9-14.9 months did not portend a worse OS than a PSADT ≥15 months (HR 0.85, p=0.60). Additionally, a PSADT of <3 months (HR 544.34, 95% CI 26.8-11042.74, p<0.001) and 9-14.9 months (HR 16.31. 95% CI 2.47-113.26, p=0.004) were found to be associated with prostate cancer-specific survival. CONCLUSIONS Among an older, racially diverse cohort of men, those who recur with a PSADT <3 months are at increased risk of overall mortality and those who recur with a PSADT of 3-8.9 months have a borderline increased risk of overall mortality. Additionally, although the number of men who died of prostate cancer was very small in this study, we identified a very strong correlation between a PSADT of <9 months and worse prostate cancer-specific survival. Thus, PSADT is a useful tool for identifying men who are at increased risk of overall and prostate cancer-specific mortality early in the course of their disease. Moreover, these findings validate prior results from tertiary care referral centers regarding the importance of PSADT as a prognostic tool. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e800-e801 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anna Teeter Durham, NC More articles by this author William Aronson Los Angeles, CA More articles by this author Joseph Presti Palo Alto, CA More articles by this author Martha Terris Augusta, GA More articles by this author Christopher Amling Portland, OR More articles by this author Christopher Kane San Diego, CA More articles by this author Stephen Freedland Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...