Association of baseline perineural invasion with shorter time to progression in men with prostate cancer undergoing active surveillance: Results from the REDEEM study.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 23-23
Author(s):  
Daniel M. Moreira ◽  
Neil Eric Fleshner ◽  
Stephen J. Freedland
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Perineural Invasion ◽  
Cox Model ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Expectant Management ◽  
Time To Progression ◽  
Kaplan Meier

23 Background: Perineural invasion (PNI) on prostate cancer (PC) biopsies has been associated with disease upgrading among those undergoing radical prostatectomy. However, the clinical significance of PNI in men on active surveillance (AS) has been evaluated by a limited number of studies. Thus, we sought to evaluate the association of PNI with time to clinical and pathological progression in men with PC on AS. Methods: Retrospective analysis of 289 men 48 to 82 years old on AS for low-risk PC (T1c-T2a), Gleason ≤6, ≤3 positive cores, ≤50% of any core involved, prostate-specific antigen (PSA) ≤11ng/ml, life expectancy >5 years and follow-up data in the REduction by Dutasteride of clinical progression Events in Expectant Management study. Progression was divided in pathological (>3 positive cores, >50% core involvement or Gleason >6 in a repeat biopsy) or therapeutic (any treatment for PC) or both. Time to progression was analyzed with Kaplan-Meier plots, log-rank tests and Cox model adjusting for age, PSA density, percent cores involved, maximum core involvement and treatment. Results: A total of 11 (4%) patients had PNI on baseline biopsy. PNI was associated with higher tumor length and maximum core involvement (all P<0.05). PNI was not associated with patient’s age, race, PSA levels or density, percent or number of positive cores. After a median follow-up of 37 months, 125 (43%) patients developed progression. Of these, 95 (76%) patients had pathological and 30 (24%) had therapeutic progression. In univariable analysis, patients with baseline PNI had a shorter time to overall and pathological progression (HR=2.62, 95%CI=1.31-5.23, P=0.006 and HR=2.42, 95%CI=1.03-5.66, P=0.041, respectively). Similar results were obtained in multivariable analysis for overall and pathological progression (HR=2.26, 95%CI=1.10-4.68, P=0.028 and HR=2.13, 95%CI=0.88-5.13, P=0.092, respectively). Conclusions: Among patients with PC on AS, PNI is independently associated with shorter time to progression. Thus, PNI may be used to help select patients for AS and stratify them according to the risk of disease progression.

Survival in metastatic castration resistant prostate cancer (mCRPC) trial participants.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15136-e15136
Author(s):  
Carmel Jo Pezaro ◽  
Aurelius Gabriel Omlin ◽  
Deborah Mukherji ◽  
Diletta Bianchini ◽  
Shahneen Kaur Sandhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Data ◽  
Cox Model ◽  
Performance Status ◽  
Specific Antigen ◽  
Trial Participation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Base Management

e15136 Background: Median overall survival (mOS) in patients (pts) with metastatic prostate cancer progressing despite castrate levels of testosterone (mCRPC) was 13-16 months (m) in the pre-docetaxel era. These data, obtained from clinical trials, were used to construct currently available prognostic nomograms. We hypothesise that these models no longer reflect survival. Pts and physicians urgently require updated prognostic data on which to base management decisions. Methods: Pts with mCRPC treated on phase I-III trials at our institution were identified and data retrospectively collected. Predicted survival by Halabi and Smaletz nomograms were compared to calculated survival using Kaplan-Meier analysis. Cox model multivariate (MV) analysis used variables at referral, including performance status (PS), Gleason (GS), prostate specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), hemoglobin (Hb), visceral disease and albumin. Results: 423 pts with CRPC treated between 2003 and 2011 were included. At diagnosis median age was 62 years (y; 41.8 – 82.7); 226 (53.4%) had metastatic disease. Median interval from diagnosis to CRPC was 2.7y (0.2 – 21.7). At referral 248 pts (58.6%) were chemotherapy-naïve. Halabi and Smaletz models predicted mOS in chemo-naïve pts of 21m and 18m respectively, however the observed mOS was 32m (95%CI 28 – 38). Survival from CRPC was 43m (CI 37 – 46) and 39m (CI 34 - 44) in pre- and post-chemo pts, respectively. Conclusions: Despite aggressive disease characteristics, our pts lived significantly longer than predicted by current nomograms. MV analysis confirmed the importance of several previously identified prognostic factors. Survival data from this large cohort of CRPC pts should encourage men considering clinical trial participation. Previously developed nomograms no longer accurately predict survival.

Associations between uncertainty, anxiety, and quality of life in men with favorable-risk prostate cancer on active surveillance: Two-and-a-half years' follow-up.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 135-135
Author(s):  
Patricia A. Parker ◽  
John W. Davis ◽  
David Latini ◽  
George Baum ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Active Surveillance ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Study Entry ◽  
Illness Uncertainty ◽  
Disease Specific

135 Background: Active surveillance (AS) has emerged as a viable option for many men with early stage prostate cancer (PC). This approach of careful monitoring with prostate-specific antigen (PSA) level, digital rectal examination, and prostate biopsy may allow men to avoid or delay the potentially debilitating side effects of such aggressive treatments as surgery or radiation; however, AS may create uncertainty and anxiety for men with PC. We examined the associations between illness uncertainty and anxiety and general and PC-specific quality of life (QOL) of 191 men with favorable-risk PC participating in the AS program at MD Anderson Cancer Center. Methods: Men completed measures of uncertainty (Mishel Uncertainty in Illness Scale), anxiety (State-Trait Anxiety Inventory), and general (SF-12, Physical Health [PCS] and Mental Health Component Score [MCS]) and disease-specific (Expanded Prostate Index Composite [EPIC]) QOL questionnaires upon study entry and every 6 months. These results are through a 2.5 year follow-up. Results: Men were primarily (86%) white and an average age of 67.2 (SD=8.9). Average baseline PSA was 3.3 ng/mL (SD=1.6), 98% had a Gleason score of 6, and 85% had cT1c disease. Both general and PC-specific QOL were relatively unchanged across the 2.5 year study period, except for statistically significant declines in the EPIC Sexual score (p<0.05). Controlling for demographic (age, ethnicity) and clinical characteristics (study entry PSA, PSA density, testosterone, BMI, baseline number of biopsies, family history of cancer, whether patients were taking a 5-alpha-reductase inhibitor, and whether the tumor was reclassified during the study), illness uncertainty was a significant predictor of all EPIC summary scores, PCS, and MCS (all, p<0.05). Anxiety was also a significant predictor of all EPIC summary scores and MCS (all, p<0.05), but not PCS (p=0.08). Conclusions: Both increased anxiety and increased illness uncertainty were associated with poorer general and disease specific QOL. Interventions that focus on reducing uncertainty and anxiety may enhance the QOL of men on AS for PC.

scholarly journals Changes in Prostate Cancer Grade on Serial Biopsy in Men Undergoing Active Surveillance

2011 ◽  
Vol 29 (20) ◽  
pp. 2795-2800 ◽  
Author(s):  
Sima P. Porten ◽  
Jared M. Whitson ◽  
Janet E. Cowan ◽  
Matthew R. Cooperberg ◽  
Katsuto Shinohara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Sampling Error ◽  
Survival Rates ◽  
Specific Antigen ◽  
Extended Period ◽  
Low Risk ◽  
Gleason Grade

Purpose Active surveillance is now considered a viable treatment option for men with low-risk prostate cancer. However, little is known regarding changes in Gleason grade on serial biopsies over an extended period of time. Patients and Methods Men diagnosed with prostate cancer between 1998 and 2009 who elected active surveillance as initial treatment, with 6 or more months of follow-up and a minimum of six cores at biopsy, were included in analysis. Upgrading and downgrading were defined as an increase or decrease in primary or secondary Gleason score. Means and frequency tables were used to describe patient characteristics, and treatment-free survival rates were determined by life-table product limit estimates. Results Three hundred seventy-seven men met inclusion criteria. Mean age at diagnosis was 61.9 years. Fifty-three percent of men had prostate-specific antigen of 6 ng/mL or less, and 94% had Gleason score of 6 or less. A majority of men were cT1 (62%), had less than 33% of biopsy cores involved (80%), and were low risk (77%) at diagnosis. Median number of cores taken at diagnostic biopsy was 13, mean time to follow-up was 18.5 months, and 29% of men had three or more repeat biopsies. Overall, 34% (129 men) were found to have an increase in Gleason grade. The majority of men who experienced an upgrade (81%) did so by their second repeat biopsy. Conclusion A proportion of men experience an upgrade in Gleason score while undergoing active surveillance. Men who experience early upgrading likely represent initial sampling error, whereas later upgrading may reflect tumor dedifferentiation.

scholarly journals Tumor-Associated Release of Prostatic Cells into the Blood after Transrectal Ultrasound-Guided Biopsy in Patients with Histologically Confirmed Prostate Cancer

2019 ◽  
Vol 66 (1) ◽  
pp. 161-168 ◽  
Author(s):  
Simon A Joosse ◽  
Burkhard Beyer ◽  
Christin Gasch ◽  
Paulina Nastały ◽  
Andra Kuske ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Prostate Biopsy ◽  
Standard Procedure ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Ultrasound Guided ◽  
Systemic Spread

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.

scholarly journals Seven-Month Prostate-Specific Antigen Is Prognostic in Metastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation With or Without Docetaxel

2018 ◽  
Vol 36 (4) ◽  
pp. 376-382 ◽  
Author(s):  
Lauren C. Harshman ◽  
Yu-Hui Chen ◽  
Glenn Liu ◽  
Michael A. Carducci ◽  
David Jarrard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Prostate Specific Antigen ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Androgen Ablation ◽  
Hormone Sensitive ◽  
Low Volume

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.

Effect of dutasteride on prostate cancer progression and cancer diagnosis on rebiopsy in the REDEEM active surveillance study.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
N. Fleshner ◽  
M. S. Lucia ◽  
K. Melich ◽  
I. M. Nandy ◽  
L. Black ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Cancer Progression ◽  
Primary Endpoint ◽  
Expectant Management ◽  
Time To Progression ◽  
Clinical Progression ◽  
Reduced Time ◽  
Prostate Cancer Study

2 Background: The REDEEM (Reduction by Dutasteride of Clinical Progression Events in Expectant Management of Prostate Cancer) study tested whether dutasteride controlled growth of existing low risk, localized prostate cancer (PCa) and hence reduced the need for aggressive therapy in men followed with active surveillance. Methods: 302 men, aged 48–82, with PSA <11 ng/ml, and Gleason score ≤6 PCa (≤3 cores positive, <50% of any core positive) were randomized to dutasteride or placebo for 3 years. Repeat 12-core biopsies were performed at 18 and 36 months, or for-cause at other times during the study. The primary endpoint was time to progression, defined as the earliest of either pathological progression (Gleason score >6, ≥4 cores positive, or >50% of any core positive) or therapeutic progression (radical prostatectomy, radiation therapy, or hormonal ablation). Results: 96% of subjects reached the primary endpoint or had a post-baseline biopsy. Dutasteride reduced time to PCa progression (relative risk reduction 38.9%, 95% CI: 12.4–57.4%, P=0.007). The table presents incidence of progression and Gleason score on final biopsy. 23% of men (N=31) in the placebo group and 36% of men (N=50) in the dutasteride group had no cancer detected on their final biopsy. PCa-related anxiety was reduced in the dutasteride arm compared to the placebo arm (P=0.036), based on the Memorial Anxiety Scale for PCa (MAX-PC). Drug-related adverse events were similar to those previously reported for dutasteride. Conclusions: In men followed with active surveillance, dutasteride delayed the time to PCa progression, increased the percent of men with no detectable PCa, and improved PCa-related anxiety. There was no evidence of increased Gleason score upgrading with dutasteride. Dutasteride may provide a useful adjunct to active surveillance for management of PCa. [Table: see text] [Table: see text]

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 ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Linear Trend ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Continuous Variable ◽  
Castration Resistant Prostate Cancer ◽  
Increased Risk ◽  
Bone Scans ◽  
Practice Methods

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.

Prostate-Specific Antigen Kinetics During Follow-Up Are an Unreliable Trigger for Intervention in a Prostate Cancer Surveillance Program

2010 ◽  
Vol 28 (17) ◽  
pp. 2810-2816 ◽  
Author(s):  
Ashley E. Ross ◽  
Stacy Loeb ◽  
Patricia Landis ◽  
Alan W. Partin ◽  
Jonathan I. Epstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Sensitivity And Specificity ◽  
Active Surveillance ◽  
Gleason Score ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Cancer Surveillance ◽  
Surveillance Program

Purpose To assess the predictive ability of prostate-specific antigen (PSA) velocity (PSAV) and doubling time (PSADT) for biopsy progression and adverse pathology at prostatectomy among men with low-risk prostate cancer enrolled on an active-surveillance program. Methods We evaluated 290 men who met criteria for active surveillance (ie, PSA density < 0.15 ng/mL/cm3 and Gleason score ≤ 6 with no pattern ≥ 4, involving ≤ 2 cores with cancer, and ≤ 50% involvement of any core by cancer) with two or more serial PSA measurements after diagnosis from 1994 to 2008. Follow-up included twice-yearly digital rectal exam and PSA measurements and yearly surveillance biopsy. Treatment was recommended for biopsy progression (ie, Gleason score ≥ 7, or > 2 positive cores, or > 50% core involvement). Sensitivity and specificity of postdiagnostic PSAV and PSADT were explored by using receiver operating characteristic (ROC) analysis. Results Overall, 188 (65%) men remained on active surveillance, and 102 (35%) developed biopsy progression at a median follow-up of 2.9 years. PSADT was not significantly associated with subsequent adverse biopsy findings (P = .83), and PSAV was marginally significant (P = .06). No PSAV or PSADT cut point had both high sensitivity and specificity (area under the curve, 0.61 and 0.59, respectively) for biopsy progression. In those who eventually underwent radical prostatectomy, PSAV (P = .79) and PSADT (P = .87) were not associated with the presence of unfavorable surgical pathology. Conclusion Postdiagnostic PSA kinetics do not reliably predict adverse pathology and should not be used to replace annual surveillance biopsy for monitoring men on active surveillance.

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