Association of prostate specific-antigen doubling time (PSADT) with metastasis-free survival (MFS) and overall survival (OS) in non-metastatic castration-resistant prostate cancer (nmCRPC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16525-e16525 ◽  
Author(s):  
Jennifer H Lin ◽  
Brian Macomson ◽  
Ozgur Tunceli ◽  
Chris Pericone ◽  
Ajay S. Behl ◽  
...  

e16525 Background: For optimal nmCRPC management, it is important to assess the rate of disease progression and its predictors. MFS and OS endpoints are likely to be important determinants in evaluating the relative impact of treatments in nmCRPC patients. This study assessed the association of PSADT with MFS and OS in real world practice. Methods: A retrospective cohort study of men ≥18 years old was conducted using the Optum electronic health record (EHR) database (2007-2016). nmCRPC was defined as a prostate cancer diagnosis, no ICD-9/10 code or therapy indicating metastatic disease, a testosterone (T) level < 50 ng/dL (castrate level) and 2 rising PSAs (relative rise ≥25%; absolute rise ≥2 ng/mL above nadir) ≥1 week apart. Baseline PSADT, calculated from the PSA nadir until 2nd rise of PSA, was grouped into < 6, 6-18 or > 18 months. A Cox proportional hazard model was used to assess the association of baseline PSADT with MFS and OS, comparing PSADT < 6 and 6-18 months against PSADT > 18 months. Multivariable analysis was adjusted for age, race, comorbidity index score, T levels, therapy and bone scans before nmCRPC. A linear trend was tested by taking PSADT as a continuous variable (median value in each group) in the model. Results: A total of 901 patients were identified. Mean nmCRPC onset age was 76 years and mean follow-up time was 2 years. The median PSADT was 7 months, ranging from 0.5 to 267 months. During follow-up, 477 patients developed metastasis and 384 died. MFS was 89%, 60%, and 47% at year 1, 3 and 5, respectively. Men with PSADT < 6 and 6-18 months had ≥50% increased risk of shorter MFS than men with PSADT > 18 months; hazard ratios (HR) were 1.87 (95% confidence interval [CI]: 1.39-2.54) and 1.50 (95%CI: 1.11-2.04), respectively. OS was 87%, 64% and 57% at year 1, 3 and 5, respectively. Shorter PSADT was associated with shorter OS (p for trend < 0.001). Men with a PSADT < 6 months had a 2-fold increased risk for decreased OS (HR = 2.04, 95% CI: 1.44-2.90). Conclusions: Patients with nmCPRC with shorter PSADT had significantly shorter MFS and OS compared to those with longer PSADT. Baseline PSADT may serve as a predictor for nmCRPC progression.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 203-203
Author(s):  
Edoardo Francini ◽  
Kathryn P. Gray ◽  
Grace Shaw ◽  
Carolyn Evan ◽  
Anis Hamid ◽  
...  

203 Background: From 2004 to 2009, mCRPC treatment options were limited to docetaxel (D), mitoxantrone, first generation anti-androgens (AA), estrogens, steroids, and ketoconazole, with only D showing OS benefit. Since 2010, five new therapies prolonged OS and were approved for mCRPC: sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide, and radium 223. We sought to assess the aggregate impact of new therapies on OS. Methods: We used the DFCI CRIS database to identify cohorts of pts who developed mCRPC between 2004-2007 (cohort A) and 2010-2013 (cohort B). Therapies for mCRPC in each cohort were annotated. Given the median follow-up (FU) was 10.6 years (yrs) in cohort A and 4.6 yrs in cohort B, we evaluated OS, defined as time from mCRPC per PCWG3 criteria to death from all causes or last follow-up visit within 5 yrs (truncated OS). Kaplan-Meier method estimated the time to events distribution with median (95% CI). Cox proportional hazards model evaluated effects of treatment groups on disease outcomes with estimates of hazard ratio (95% CI). Results: Of the 583 pts identified, 317 (54%) were in cohort A and 266 (46%) in cohort B. Pts in cohort B had a significantly longer median OS (p<0.001), a 5-yr OS of 26% vs. 10%, and a 31% reduced risk of death compared to cohort A (HR=0.69; 95% CI, 0.57-0.83) (see Table). On multivariable analysis, adjusting for prior local Rx, ECOG PS, and the number of agents received, longer OS is confirmed associated with cohort B vs. A and also with ECOG PS status 0 vs. 1, number of agents received 5-12 vs. ≤3. Conclusions: Using the DFCI prostate cancer database, therapies approved for mCRPC since 2010 showed a modest impact on OS, with a median improvement of 6 months. There was a more substantial effect on long term survivors with 2.6 fold increase of 5-yr OS. [Table: see text]


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 126-126 ◽  
Author(s):  
Mark N. Stein ◽  
Lawrence Fong ◽  
Anthony E. Mega ◽  
Elaine Tat Lam ◽  
John W. Heyburn ◽  
...  

126 Background: ADXS-PSA, an attenuated Listeria monocytogenes-based immunotherapy targeting prostate-specific antigen (PSA), is currently being evaluated in combination with pembrolizumab as a treatment for progressive metastatic castration-resistant prostate cancer (mCRPC) in the phase 1/2 KEYNOTE-046 trial (Part B). Methods: A total of 37 patients received 1x109 CFU + 200 mg pembro IV every 3 wks, for up to 2 yrs or until progression/toxicity. Results: At entry, patients were ~70 yrs with median a Gleason score of 9, and bone predominant disease (70%). MSI-High was negative in 36 pts who were able to be tested. Eighteen (48.6%) patients had received prior docetaxel, 15 pts of whom (83.3%) had also received 1-2 next generation hormonal agents (NGHAs). Nineteen (51.3%) had not received prior docetaxel and 16 of these pts (84.2%) had received 1-2 NGHAs. Overall, 16 out of 37 pts (43%) had a decreased PSA post-BL with 6/37 (16%) pts achieving a confirmed PSA reduction ≥50% from baseline. The median OS (months) for the whole group (37 pts) was 33.6 m (95% CI, range 15.4-33.6 months). The mOS for pts with and without prior exposure to docetaxel was 16 m (5.9 -33.6) and NR at 30 months of follow-up (15.4-NR), respectively. Prolonged survival was observed in pts regardless of prior therapies, microsatellite stable (MSS) status or PSA delta <50% or ≥50%. Conclusions: Results with ADXS-PSA in combination with pembrolizumab in mCRPC, with or without prior docetaxel, show promising clinical activity to be further assessed in randomized studies. Clinical trial information: NCT02325557.


2014 ◽  
Vol 32 (27) ◽  
pp. 3033-3038 ◽  
Author(s):  
Mohummad Minhaj Siddiqui ◽  
Kathryn M. Wilson ◽  
Mara M. Epstein ◽  
Jennifer R. Rider ◽  
Neil E. Martin ◽  
...  

Purpose Conflicting reports remain regarding the association between vasectomy, a common form of male contraception in the United States, and prostate cancer risk. We examined prospectively this association with extended follow-up and an emphasis on advanced and lethal disease. Patients and Methods Among 49,405 US men in the Health Professionals Follow-Up Study, age 40 to 75 years at baseline in 1986, 6,023 patients with prostate cancer were diagnosed during the follow-up to 2010, including 811 lethal cases. In total, 12,321 men (25%) had vasectomies. We used Cox proportional hazards models to estimate the relative risk (RR) and 95% CIs of total, advanced, high-grade, and lethal disease, with adjustment for a variety of possible confounders. Results Vasectomy was associated with a small increased risk of prostate cancer overall (RR, 1.10; 95% CI, 1.04 to 1.17). Risk was elevated for high-grade (Gleason score 8 to 10; RR, 1.22; 95% CI, 1.03 to 1.45) and lethal disease (death or distant metastasis; RR, 1.19; 95% CI, 1.00 to 1.43). Among a subcohort of men receiving regular prostate-specific antigen screening, the association with lethal cancer was stronger (RR, 1.56; 95% CI, 1.03 to 2.36). Vasectomy was not associated with the risk of low-grade or localized disease. Additional analyses suggested that the associations were not driven by differences in sex hormone levels, sexually transmitted infections, or cancer treatment. Conclusion Our data support the hypothesis that vasectomy is associated with a modest increased incidence of lethal prostate cancer. The results do not appear to be due to detection bias, and confounding by infections or cancer treatment is unlikely.


2019 ◽  
Vol 66 (1) ◽  
pp. 161-168 ◽  
Author(s):  
Simon A Joosse ◽  
Burkhard Beyer ◽  
Christin Gasch ◽  
Paulina Nastały ◽  
Andra Kuske ◽  
...  

Abstract BACKGROUND Transrectal ultrasound-guided prostate biopsy (TRUS) is a standard procedure for prostate cancer diagnosis. Because prostate cancer is a multifocal disease in many patients, multiple sampling (n ≥ 10) is required, which may bear the risk of systemic spread of cancer cells. DESIGN Using the standardized CellSearch® system that allows for the detection of single epithelial cell adhesion molecule-positive circulating tumor cells (CTCs) in blood, we investigated whether prostate biopsy is associated with release of prostatic tumor cells into the circulation. Peripheral blood was obtained before and within 30 min after performing prostate biopsy from 115 men with increased serum prostate-specific antigen. RESULTS The number of CTCs significantly increased after biopsy in men with histologically confirmed prostate cancer (odds ratio, 7.8; 95% CI, 4.8–12.8), whereas no biopsy-related changes could be detected in men without confirmed prostate cancer. Multivariable analysis showed that biopsy-related increase of CTCs was significantly correlated with a worse progression-free survival (hazard ratio, 12.4; 95% CI, 3.2–48.6) within the median follow-up of 41 months. CONCLUSIONS Prostate biopsies may lead to a tumor-associated release of CTCs into the blood circulation. Larger confirmatory trials with longer follow-up periods are required before any change in clinical practice can be recommended.


2018 ◽  
Vol 36 (4) ◽  
pp. 376-382 ◽  
Author(s):  
Lauren C. Harshman ◽  
Yu-Hui Chen ◽  
Glenn Liu ◽  
Michael A. Carducci ◽  
David Jarrard ◽  
...  

Purpose We evaluated the relationship between prostate-specific antigen (PSA) and overall survival in the context of a prospectively randomized clinical trial comparing androgen-deprivation therapy (ADT) plus docetaxel with ADT alone for initial metastatic hormone-sensitive prostate cancer. Methods We performed a landmark survival analysis at 7 months using the E3805 Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) database ( ClinicalTrials.gov identifier: NCT00309985). Inclusion required at least 7 months of follow-up and PSA levels at 7 months from ADT initiation. We used the prognostic classifiers identified in a previously reported trial (Southwest Oncology Group 9346) of PSA ≤ 0.2, > 0.2 to 4, and > 4 ng/mL. Results Seven hundred nineteen of 790 patients were eligible for this subanalysis; 358 were treated with ADT plus docetaxel, and 361 were treated with ADT alone. Median follow-up time was 23.1 months. On multivariable analysis, achieving a 7-month PSA ≤ 0.2 ng/mL was more likely with docetaxel, low-volume disease, prior local therapy, and lower baseline PSAs (all P ≤ .01). Across all patients, median overall survival was significantly longer if 7-month PSA reached ≤ 0.2 ng/mL compared with > 4 ng/mL (median survival, 60.4 v 22.2 months, respectively; P < .001). On multivariable analysis, 7-month PSA ≤ 0.2 and low volume disease were prognostic of longer overall survival (all P < 0.01). The addition of docetaxel increased the likelihood of achieving a PSA ≤ 0.2 ng/mL at 7 months (45.3% v 28.8% of patients on ADT alone). Patients on ADT alone who achieved a 7-month PSA ≤ 0.2 ng/mL had the best survival and were more likely to have low-volume disease (56.7%). Conclusion PSA ≤ 0.2 ng/mL at 7 months is prognostic for longer overall survival with ADT for metastatic hormone-sensitive prostate cancer irrespective of docetaxel administration. Adding docetaxel increased the likelihood of a lower PSA and improved survival.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1581-1581
Author(s):  
Melissa Pirolli ◽  
Rohini Khorana Hernandez ◽  
Karynsa Cetin ◽  
Jane Quigley ◽  
Yanina Grant-Huerta ◽  
...  

1581 Background: Prostate-specific antigen (PSA) is a well-known PC biomarker. In the M0 setting, rising PSAs despite ADT is an indication of the development of castration-resistant prostate cancer (CRPC). In this disease state, men are at risk for developing bone metastasis (BM), which is associated with significant morbidity and may negatively affect survival. Using real-world data, we explored PSA-based criteria to identify patients who develop CRPC while on ADT and the subsets that may be at increased risk of BM. Methods: We used the Oncology Services Comprehensive Electronic Records (OSCER) database, which includes electronic medical record (EMR) data on cancer patients from 328 urology and oncology clinics in the US. Eligible patients were adult men with M0 PC with ≥1 PSA recorded between 3/1/2010 and 2/28/2011 and currently receiving ADT (gonadotropin-releasing hormone agonists or bilateral orchiectomy) for ≥6 months (mos). We defined CRPC as two sequential PSA rises while on ADT and high risk for BM as any PSA ≥8 ng/mL or PSA doubling time (DT) ≤10 mos, as described by Smith MR et al, Lancet 2012. We explored subsets of CRPC patients who may be at even higher risk of BM using PSA thresholds (≥8 ng/mL and ≥20 ng/mL) and DT (≤4, 6, 8, and 10 mos). Results: Of 1,818 men with M0 PC receiving ADT ≥6 mos, 36% (N=646) met the CRPC definition, of whom 80% (N=517) had PSA ≥8 ng/mL and/or PSA DT ≤10 mos (high risk). PSA DT alone explained 63% (44% / 70%) to 93% (65% / 70%) of subgroup eligibility (Table), and emerged as a main driver in defining increased risk of BM for CRPC subsets. Conclusions: In this analysis of EMR data, over one-third of men with M0 PC on ADT met criteria for CRPC, and most CRPC patients (80%) may be considered at high risk for BM. Requiring ≥3 PSAs to define CRPC may be a limitation; however, because PSAs are closely monitored in patients on ADT, these definitions of CRPC and high risk may be useful in practice. These data suggest that PSA DT may be a more clinically meaningful measure of defining CRPC subsets than absolute PSA thresholds. [Table: see text] .


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 161-161
Author(s):  
Johann S. De Bono ◽  
Klaus Pantel ◽  
Eleni Efstathiou ◽  
Cora N. Sternberg ◽  
Daniel Castellano ◽  
...  

161 Background: In the prospective CARD trial (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer who had received docetaxel and progressed within 12 months with the alternative androgen-signaling-targeted inhibitor. Here we analyzed circulating tumor cell (CTC) counts as a biomarker of prognosis and response to therapy. Methods: Blood samples collected at screening (SC), Cycle 2 (C2) Day 1, and end of therapy were sent to Epic Sciences for CTC analysis. The association between CTC counts, defined as any cytokeratin-positive, CD45-negative cell, and clinical outcomes were pre-specified and analyzed using a multivariate Cox model for time-to-events (rPFS, OS) or a Χ2 test for categorical outcomes (objective tumor response). Results: Of the 255 patients randomized, 237 (92.9%) had evaluable samples at SC and 213 (83.5%) at C2. CTCs ≥ 1 were detected in 204 samples at SC (86%) and 178 samples at C2 (84%), with a median (interquartile range) count per mL of blood of 4.1 (1.3–14.2) and 5.2 (1.5–17.3), respectively. At baseline, higher CTC counts were associated with higher values of lactate dehydrogenase (P = 0.014), alkaline phosphatase (P < 0.001), and prostate-specific antigen (P < 0.001). High CTC counts, measured as a continuous variable at SC (all arms combined) were associated with a shorter OS (P = 0.03), but not rPFS (P = 0.7). However, favorable changes in absolute CTC count from SC to C2, all arms combined, were associated with longer rPFS (P = 0.03). Conversion from high (≥ 3) to low (< 3) CTC count at C2 or maintenance of a low CTC count at C2 was associated with objective tumor response (P = 0.007). Analysis of the associations of CTC androgen receptor variant 7, chromosomal instability, heterogeneity status (Shannon Index), single-cell genotypes (e.g. retinoblastoma/phosphatase and tensin homolog copy-loss), and the presence of CTCs with small-cell/neuroendocrine morphology is ongoing. Conclusions: This preplanned analysis of the CARD trial confirms that baseline CTC counts, measured by Epic Sciences platform, are prognostic. Moreover, early favorable changes in CTC counts from baseline to C2 are associated with response to therapy. Funding: Sanofi. Clinical trial information: NCT02485691.


2014 ◽  
Vol 8 (9-10) ◽  
pp. 583 ◽  
Author(s):  
Ravinder Clayton ◽  
Jackson Wu ◽  
Daniel Y Heng ◽  
Scott A North ◽  
Urban Emmenegger ◽  
...  

Introducton: The COU-AA-301 trial showed that abiraterone acetate (abiraterone), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel. To better understand the non-clinical trial experience with abiraterone, we undertook a multicentre retrospective analysis of Canadian mCRPC patients treated with abiraterone.Methods: Consecutive patients with mCRPC who received abiraterone post-docetaxel were identified using centralized pharmacy records. These patients came from 5 Canadian tertiary cancer centres. Patients who received abiraterone for approved indications were included. Demographics, prognostic factors, treatment outcomes and adverse events were abstracted.Results: We included 187 patients who initiated abiraterone between January 2011 and June 2012. The median age at diagnosis and abiraterone start was 65 and 73 years, respectively. Seventy-three (39%) patients had metastatic disease at diagnosis. The Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 and 3 was noted in 17, 96, 39 and 8 patients, respectively. The median prostate-specific antigen (PSA) at abiraterone start was 132, with a median PSA doubling time of 2.8 months. The median follow-up of patients still on active follow-up was 13 months. The proportion of patients achieving a ≥50% PSA reduction was 64/177 (36%). PSA progression-free survival was 3.5 months (95% confidence interval [CI], 3.0, 4.0). Median overall survival from start of abiraterone was 11 months (95% CI, 8.0, 13) and 38 months (95% CI, 31, 41) from date of mCRPC. Anemia and fatigue were the most commonly reported adverse events.Conclusions: This study carries the inherent limitations of a retrospective chart review. The outcomes in this series of men treated with abiraterone in a non-trial setting were expected, considering previous clinical trials. Our results, therefore, support the generalizability of the COU-AA-301 study results.


2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Patranuch Noppakulsatit

Purpose: To evaluate the influence of nadir prostate-specific antigen (PSA) level and time to PSA nadir following androgen deprivation therapy (ADT)on disease progression of castration-resistant prostate cancer (CRPC) in patients with metastatic, hormone-sensitive prostate cancer (mHSPC). Patients and methods: A total of 90 patients with metastatic, hormone-sensitive prostate cancer treated with androgen deprivation therapy in our hospital were included in our retrospective study. Patients’ characteristics, PSA at PADT initiation (initial PSA), PSA nadir, TTN, follow up time, CRPC event were analyzed using Kaplan-Meier analysis and Cox regression model. Results: At a median follow-up of 12 months, 57 patients (63.3%) showed disease progression of CRPC Both PSA nadir and time to PSA nadir (TTN) was independent and significant predictors of CRPC event. Patients with higher PSA nadir (≥0.2ng/dL) and shorter time to PSA nadir (TTN <6 months) had significant shorter time to CRPC. Meanwhile, the Gleason score, age and initial PSA werenot significant predictors of disease progression. In the combined analyses showed patients with higher of PSA nadir and shorter TTN had significantly higher risk for CRPC event compared to lower PSA nadir and longer TTN (HR 69.243, p-value< 0.001) Conclusion: We concluded that both higher PSA nadir and shorter time to PSA nadir are significant predictors of CRPC in patients with metastatic, hormone-sensitive prostate cancer receiving ADT.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 257-257
Author(s):  
Rimaz M. Khadir ◽  
Rashid K. Sayyid ◽  
Martha K. Terris

257 Background: Sedentary behavior has been associated with increased serum prostate-specific antigen (PSA) levels. It is currently unknown whether this correlates with an increased risk of underlying prostate cancer (PCa). Our objective was to determine whether patients with sedentary occupations presenting for a prostate biopsy were at increased risk of PCa diagnosis. Methods: A prospectively collected registry of patients undergoing a prostate biopsy between July 1995 and June 2016 at the Veterans Affairs Medical Center in Augusta, GA was utilized. The occupation was classified as sedentary if it was associated with prolonged periods of sitting (i.e. >50% work hours). This was determined via patient reported history at time of biopsy. The associations between a sedentary lifestyle and risk of a positive prostate biopsy, high grade cancer (i.e. Gleason score 8 or higher), and high volume cancer (i.e. at least 50% of total cores were positive) were evaluated using multivariable logistic regression analyses, controlling for age, race, body mass index, PSA level, free PSA ratio, clinical stage, prostate volume, and family history of prostate cancer. Statistical significance was set at p<0.05. All statistical analyses were performed using R version 3.6.1. Results: Our cohort included 1,914 patients. 271 (14.2%) patients had sedentary jobs. Median patient age was 61.0 years (Interquartile range [IQR] 57.0 – 66.0). Median PSA at time of biopsy was 5.7 ng/ml (IQR 4.4 – 8.2). Of the 1,914 initial biopsies performed, 974 (50.9%) were positive for malignancy. Of patients diagnosed with PCa, 229 (23.5%) had high-grade disease and 316 (32.4%) had high volume disease. On multivariable analysis, patients with a sedentary job had a significantly decreased risk of PCa diagnosis (Odds ratio [OR] 0.43, 95% confidence interval [CI] 0.18-1.03, p= 0.058), but no difference in odds of high grade (OR 0.63, 95% CI 0.089-2.99, p= 0.60) or high volume disease (OR 1.07, 95% CI 0.93-1.21, p= 0.89). Conclusions: Patients with sedentary occupations presenting for a prostate biopsy are at a lower apparent risk for a positive prostate biopsy. These results suggest that the serum PSA levels in such patients may be artificially elevated secondary to increased recumbence with no corresponding increase in risk of malignancy. [Table: see text]


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