Validation of a genomic classifier for predicting biochemical failure following postoperative radiation therapy in high-risk prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 10-10
Author(s):  
Robert Benjamin Den ◽  
Felix Yi-Chung Feng ◽  
Timothy Norman Showalter ◽  
Mark Vikas Mishra ◽  
Edouard John Trabulsi ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Background Radiation ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Biochemical Failure ◽  
Receiver Operating Curve ◽  
Gleason Grade ◽  
Tumor Focus

10 Background: Radiation therapy (RT) is commonly offered in the post radical prostatectomy (RP) setting, however response varies. We hypothesized that the genomic classifier ([GC] Decipher) score would predict biochemical failure (BF) and distant metastasis (DM) in men receiving post−RP RT. Methods: Under an institutional review board approved protocol, 223 men who underwent post−RP RT at the Kimmel Cancer Center of Thomas Jefferson University for pT3 or margin positive disease from 1990 to 2009 were identified. RNA was extracted from 143 patients with paraffin−embedded specimens and expression quantified from the highest Gleason grade tumor focus using a high−density oligonucleotide microarray. Excluding men who received neo−adjuvant therapy, 139 patients remained for GC calculation. Area under the receiver operating curve (AUC), decision curves, cumulative incidence accounting for competing risks, and multivariable Cox regression analyses were used to assess GC for predicting BF and DM after RT in comparison to nomograms. Results: The AUC of CAPRA-S was 0.67 (95% CI 0.58−0.77) and 0.65 (95% CI 0.44−0.86) for BF and DM, respectively. Integration of GC improved AUC to 0.75 (95% CI 0.66−0.84) and 0.77 (95% CI 0.64−0.91) for BF and DM, respectively. Cumulative incidence of BF at 8 years post-RT was 21%, 48%, and 81% for low (less than 0.4), intermediate (0.4 to 0.6), and high (more than 0.6) GC, respectively (p<0.00001). In multivariable analysis, patients who received RT early (pre−RT prostate-specific antigen [PSA] less than 1 ng/mL) had a BF benefit with a significantly reduced hazard ratio (HR) of 0.32 (95% CI 0.11−0.96, p<0.042). Patients with high GC had an HR of 14.73 for BF (95% CI 4.90−44.31, p<0.00001). Earlier PSA recurrence was observed in patients with high GC score that received salvage compared to adjuvant RT with median BF survival post-RT of 4.67 versus 8.78 years (p<0.04). This held true after adjusting for CAPRA-S score. Conclusions: This is the first validation of the GC in the post−RP RT setting. GC improved risk stratification above clinical classifiers. Patients with high GC received significant benefit from early RT intervention. For those patients with high pre-RT PSA and high GC, exploration of intensified therapy is warranted.

Positive margin length and Gleason grade of tumor focus at the margin predict for biochemical failure after radical prostatectomy in patients with pT2 prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 103-103 ◽  
Author(s):  
Jenny N. Nguyen ◽  
Brian Francis Chapin ◽  
Ina N. Prokhorova ◽  
Xuemei Wang ◽  
John W. Davis ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Clinical Stage ◽  
Multivariable Analysis ◽  
Positive Margin ◽  
Biochemical Failure ◽  
Cancer Center ◽  
Adjuvant Radiation ◽  
Gleason Grade ◽  
Tumor Focus

103 Background: While three prospective trials have demonstrated benefit from adjuvant radiation (XRT) after radical prostatectomy (RP) in patients with positive surgical margins (PSM), its use varies amongst physicians. Many rely on clinical acumen to determine the optimal strategy for application of XRT post RP. We aim to determine if the length of PSM and highest Gleason grade (GG) of tumor at the PSM (hGGPSM) can be used to identify patients at greatest risk of biochemical failure (BCF) post RP. Methods: A retrospective review of all RP patients at The University of Texas MD Anderson Cancer Center from 2002 to 2010 was performed. After a single pathologist review, patients with organ confined disease (pT2), pathologic N0/Nx and a PSM were included. BCF was defined as 2 sequential PSA values of ≥0.2 or any detectable PSA prompting XRT. Patients receiving adjuvant XRT or with <12 months follow-up were excluded. Results: 205 patients met the inclusion criteria. Median PSA was 5.3 ng/mL (0.5-33) and median follow-up was 64 months (13-130). The majority were low clinical stage (cT1c: 65%), low (11%)/intermediate (82%) grade and had a single site of a PSM (90%). BCF occurred in 47 patients for a 5 yr BCF free survival (BCFFS) of 69%. PSM length was significantly associated with BCFFS (≤1mm vs >1, p=0.02). When accounting for hGGPSM, Gl 3 tumors were less likely to experience BF (5 yr BCFFS-96%) regardless of PSM length, while BCFFS for Gl >3 tumors were significantly lower dependent upon length of PSM ( ≤1mm vs >1mm, p=0.03). On multivariable analysis length of PSM (p=0.05) and hGGPSM (p=0.007) remained independent predictors of BCF (Table). Conclusions: Length of PSM and hGGPSM are independent predictors of BCF. These should be considered when evaluating patients for adjuvant XRT and in risk stratifying patients in prospective clinical trials. [Table: see text]

scholarly journals Genomic Classifier Identifies Men With Adverse Pathology After Radical Prostatectomy Who Benefit From Adjuvant Radiation Therapy

2015 ◽  
Vol 33 (8) ◽  
pp. 944-951 ◽  
Author(s):  
Robert B. Den ◽  
Kasra Yousefi ◽  
Edouard J. Trabulsi ◽  
Firas Abdollah ◽  
Voleak Choeurng ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Optimal Timing ◽  
Adjuvant Radiation ◽  
Cox Regression Analysis ◽  
Pathologic Features

Purpose The optimal timing of postoperative radiotherapy (RT) after radical prostatectomy (RP) is unclear. We hypothesized that a genomic classifier (GC) would provide prognostic and predictive insight into the development of clinical metastases in men receiving post-RP RT and inform decision making. Patients and Methods GC scores were calculated from 188 patients with pT3 or margin-positive prostate cancer, who received post-RP RT at Thomas Jefferson University and Mayo Clinic between 1990 and 2009. The primary end point was clinical metastasis. Prognostic accuracy of the models was tested using the concordance index for censored data and decision curve analysis. Cox regression analysis tested the relationship between GC and metastasis. Results The cumulative incidence of metastasis at 5 years after RT was 0%, 9%, and 29% for low, average, and high GC scores, respectively (P = .002). In multivariable analysis, GC and pre-RP prostate-specific antigen were independent predictors of metastasis (both P < .01). Within the low GC score (< 0.4), there were no differences in the cumulative incidence of metastasis comparing patients who received adjuvant or salvage RT (P = .79). However, for patients with higher GC scores (≥ 0.4), cumulative incidence of metastasis at 5 years was 6% for patients treated with adjuvant RT compared with 23% for patients treated with salvage RT (P < .01). Conclusion In patients treated with post-RP RT, GC is prognostic for the development of clinical metastasis beyond routine clinical and pathologic features. Although preliminary, patients with low GC scores are best treated with salvage RT, whereas those with high GC scores benefit from adjuvant therapy. These findings provide the first rational selection of timing for post-RP RT.

scholarly journals Nadir Testosterone Within First Year of Androgen-Deprivation Therapy (ADT) Predicts for Time to Castration-Resistant Progression: A Secondary Analysis of the PR-7 Trial of Intermittent Versus Continuous ADT

2015 ◽  
Vol 33 (10) ◽  
pp. 1151-1156 ◽  
Author(s):  
Laurence Klotz ◽  
Chris O'Callaghan ◽  
Keyue Ding ◽  
Paul Toren ◽  
David Dearnaley ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Androgen Deprivation Therapy ◽  
Cox Regression ◽  
Secondary Analysis ◽  
Serum Testosterone ◽  
Androgen Deprivation ◽  
Biochemical Failure ◽  
First Year ◽  
Hormone Resistance ◽  
Significant Difference

Purpose Three small retrospective studies have suggested that patients undergoing continuous androgen deprivation (CAD) have superior survival and time to progression if lower castrate levels of testosterone (< 0.7 nmol/L) are achieved. Evidence from prospective large studies has been lacking. Patients and Methods The PR-7 study randomly assigned patients experiencing biochemical failure after radiation therapy or surgery plus radiation therapy to CAD or intermittent androgen deprivation. The relationship between testosterone levels in the first year and cause-specific survival (CSS) and time to androgen-independent progression in men in the CAD arm was evaluated using Cox regression. Results There was a significant difference in CSS (P = .015) and time to hormone resistance (P = .02) among those who had first-year minimum nadir testosterone ≤ 0.7, > 0.7 to ≤ 1.7, and ≥ 1.7 nmol/L. Patients with first-year nadir testosterone consistently > 0.7 nmol/L had significantly higher risks of dying as a result of disease (0.7 to 1.7 nmol/L: hazard ratio [HR], 2.08; 95% CI, 1.28 to 3.38; > 1.7 nmol/L: HR, 2.93; 95% CI, 0.70 to 12.30) and developing hormone resistance (0.7 to 1.7 nmol/L: HR, 1.62; 95% CI, 1.20 to 2.18; ≥ 1.7 nmol/L: HR, 1.90; 95% CI, 0.77 to 4.70). Maximum testosterone ≥ 1.7 nmol/L predicted for a higher risk of dying as a result of disease (P = .02). Conclusion Low nadir serum testosterone (ie, < 0.7 mmol/L) within the first year of androgen-deprivation therapy correlates with improved CSS and duration of response to androgen deprivation in men being treated for biochemical failure undergoing CAD.

Surgical margins and biochemical recurrence risk at 2 years for robotic prostatectomy: Comprehensive evaluation and CUSUM analysis of oncological outcomes.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 80-80
Author(s):  
Arjun Sivaraman ◽  
Rafael Sanchez-Salas ◽  
Dominic Prapotnich ◽  
Kaixin Yu ◽  
Fabien Olivier ◽  
...  
Keyword(s):  
Learning Curve ◽  
Biochemical Recurrence ◽  
Transition Point ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Surgical Margin ◽  
Positive Surgical Margin ◽  
Oncological Outcomes ◽  
Cusum Analysis

80 Background: To evaluate the learning curve of Minimally Invasive Radical Prostatectomy (MIRP) in our institution and apply the cumulative summation (CUSUM) analytical technique to identify salient learning curve transition points in terms of oncological outcomes. Methods: Clinical, pathologic, and oncological outcome data were collected from our prospectively collected MIRP database to estimate Positive Surgical margin (PSM) and Biochemical Recurrence (BCR) trends during a 15 year period from 1998 to 2013. All the RPs (laparoscopic (LRP) / Robotic Assisted [RARP]) were performed by 9 surgeons. PSM was defined as presence of cancer cells at inked margins. BCR was defined as serum Prostate Specific Antigen (PSA) >0.2 ng/ml and rising or start of secondary therapy. Surgical learning curve was assessed with the application of Kaplan-Meier curves, Cox regression model, CUSUM and logistic model in order to define the “transition point” of surgical improvement. Results: We identified 5,547 patients with localized prostate cancer treated with MIRP (3,846 - LRP and 1,701 – RARP). Patient characteristics of LRP and RARP were similar. The overall risk of PSM in LRP was 25%, 20% and 17% for the first 50, 50 to 350 and >350 cases, respectively. For the same population, the 5-year BCR rate decreased from 21.5% to 16.7%. RARP started 3 years after the LRP program (after approximately 250 LRP). The PSM rate for RARP decreased from 21.8% to 20.4% and the corresponding 5-year BCR rate decreased from 17.6% to 7.9%. The CUSUM analysis showed significantly lower PSM and BCR at 2 years occurred at the transition point of 350 cases for LRP and 100 cases for RARP. In multivariable analysis, predictors of BCR were PSA, Gleason score, extra prostatic disease, seminal vesicle invasion and number of operations (p < 0.05). Patients harboring PSM showed higher BCR risk (23% vs. 8%, p < 0.05). Conclusions: Learning curve trends of MIRP in our large, single center experience showed significant reduction in PSM and BCR risk at 2 years are noted after the initial 350 cases and 100 cases of LRP and RARP, respectively.

Benefit on Biochemical Control of Adjuvant Radiation Therapy in Patients with Pathologically Involved Seminal Vesicles after Radical Prostatectomy

2007 ◽  
Vol 93 (5) ◽  
pp. 445-451 ◽  
Author(s):  
Carlo Greco ◽  
Simona Castiglioni ◽  
Andrei Fodor ◽  
Ottavio De Cobelli ◽  
Nadia Longaretti ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Radical Prostatectomy ◽  
Seminal Vesicle ◽  
Biochemical Recurrence ◽  
Specific Antigen ◽  
Biochemical Failure ◽  
Adjuvant Radiation ◽  
Biochemical Control ◽  
Adjuvant Radiation Therapy ◽  
Seminal Vesicle Invasion

Aims and Background To determine whether there is a benefit for biochemical control with adjuvant radiation therapy to the surgical bed following radical prostatectomy in patients with seminal vesicle invasion and pathologically negative pelvic lymph nodes (pT3b-pT4 pN0). Methods We retrospectively reviewed the clinical records of radical prostatectomy patients treated between 1995 and 2002. A total of 66 patients with seminal vesicle invasion were identified: 45 of these patients received adjuvant radiation therapy and 21 were observed. Radiation therapy was initiated within 4 months of prostatectomy. Median dose was 66 Gy (range, 60–70 Gy). Median follow-up from the day of surgery was 40.6 months (mean, 41.5; range, 12–99). Biochemical recurrence was defined as the first value ≥0.2 ng/ml. Results At two years, the proportion of patients free from biochemical recurrence was 80% in patients who received adjuvant radiation therapy versus 54% for those not given radiation therapy (P = 0.036). Actuarial biochemical recurrence at 5 years was 59% vs 41% for the radiation therapy and no radiation therapy groups, respectively. On univariate Cox regression model, the hazard of biochemical failure was also associated with a detectable (≥0.2 ng/ml) postsurgical prostate-specific antigen (P = 0.02) prior to radiation therapy. Pathological T stage (pT3b vs pT4), Gleason score, primary Gleason pattern and positive surgical margins were not significantly associated with biochemical recurrence. The hazard of biochemical failure was around 85% lower in the radiation therapy group than in the observation group (P = 0.002). Conclusions Data from the present series suggest that adjuvant radiation therapy for patients with seminal vesicle invasion and undetectable (≤0.2 ng/ml) postoperative prostate-specific antigen significantly reduces the likelihood of biochemical failure.

Intermediate versus short-course hormone therapy and mortality in men with high-risk prostate cancer treated with radiation therapy.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 83-83
Author(s):  
Akash Nanda ◽  
Ming-Hui Chen ◽  
Brian Joseph Moran ◽  
Michelle H. Braccioforte ◽  
Anthony Victor D'Amico
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
High Risk ◽  
Background Radiation ◽  
Multivariable Analysis ◽  
Study Cohort ◽  
High Risk Prostate Cancer ◽  
Short Course ◽  
Risk Prostate Cancer ◽  
The Impact

83 Background: Radiation therapy (RT) plus 28-36 months of hormonal therapy (HT) is standard-of-care for men with high-risk prostate cancer (HRPC) based on randomized trials comparing these HT durations to 4-6 months. However, it is unknown whether shorter durations of HT may also decrease mortality. We evaluate the impact of intermediate-course HT on the risk of all-cause mortality (ACM) in men with HRPC treated with RT. Methods: The study cohort comprised 554 men with HRPC (PSA > 20; Gleason score 8 or higher; or clinical stage T2c or higher) consecutively treated at the Chicago Prostate Cancer Center between 1997 and 2007. All men received brachytherapy with or without external beam RT and HT of intermediate (> 6 to 24; median 12 months) or short (up to 6; median 4 months) duration. A Cox regression multivariable analysis was performed assessing whether intermediate compared to short-course HT was associated with a decreased risk of ACM, adjusting for age, year and type of RT, treatment propensity score, and known PC prognostic factors. Results: After a median follow up of 4.3 years a total of 64 (11.6%) men died. Intermediate compared to short-course HT was associated with a significantly decreased risk of ACM (adjusted hazard ratio 0.44, 95% confidence interval 0.20 - 0.94, P = 0.03). Other significant covariates are shown in the table. The 5-year estimates of ACM for intermediate versus short-course HT were 7.0% and 15.7%, respectively. Conclusions: In men with HRPC treated with RT, a median HT duration of 12 months was associated with a significantly decreased risk of ACM when compared to a median HT duration of 4 months. This raises the hypothesis that HT durations shorter than 28-36 months may be sufficient to decrease mortality in men with HRPC. The ongoing RADAR trial by the Trans Tasman Radiation Oncology Group comparing 18 to 6 months of HT may provide level I evidence to validate this hypothesis. [Table: see text]

A genomic classifier to identify men with adverse pathology post radical prostatectomy who benefit from adjuvant radiation therapy.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 168-168
Author(s):  
Robert Benjamin Den ◽  
Kasra Yousefi ◽  
Edouard John Trabulsi ◽  
Firas Abdollah ◽  
Voleak Choeurng ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
Multivariable Analysis ◽  
Optimal Timing ◽  
Adjuvant Radiation ◽  
Prognostic Accuracy ◽  
Pathologic Features ◽  
The Relationship

168 Background: The optimal timing of postoperative radiotherapy following radical prostatectomy (post-RP RT) is unclear. We hypothesized that a genomic classifier (GC) would provide prognostic and predictive insight into the development of clinical metastases in men receiving post-RP RT and inform decision-making. Methods: GC scores were calculated from 188 patients with pT3 or margin positive PCa, who received post-RP RT at Thomas Jefferson University and Mayo Clinic, between 1990 and 2009. The primary endpoint was clinical metastasis. Prognostic accuracy of the models were tested using c-index and decision curve analysis. Cox regression tested the relationship between GC and metastasis. Results: The cumulative incidence of metastasis at 5 years post-RT was 0%, 9%, and 29% for low, average, and high GC scores, respectively (p=0.002). In multivariable analysis, GC and pre-RP PSA were independent predictors of metastasis (both p<0.01). Within the low GC score (<0.4), there were no differences in the cumulative incidence of metastasis comparing those who received adjuvant or salvage RT (p=0.79). However, for patients with higher GC scores (≥0.4) cumulative incidence of metastasis at 5-year was 6% vs. 23% for patients treated with adjuvant vs. salvage RT (p<0.01). Conclusions: In patients treated with post-RP RT, GC is prognostic for the development of clinical metastasis beyond routine clinical/pathologic features. Though preliminary, patients with low GC are best treated with salvage radiation, while those with high GC benefit from adjuvant therapy. These findings provide the first rationale selection of timing of post-RP RT.

Utilizing Predictions of Early Prostate-Specific Antigen Failure to Optimize Patient Selection for Adjuvant Systemic Therapy Trials

2000 ◽  
Vol 18 (18) ◽  
pp. 3240-3246 ◽  
Author(s):  
Anthony V. D’Amico ◽  
Richard Whittington ◽  
S. Bruce Malkowicz ◽  
Yue Hui Wu ◽  
Ming-Hui Chen ◽  
...  
Keyword(s):  
Prostate Specific Antigen ◽  
Confidence Intervals ◽  
Systemic Therapy ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Adjuvant Systemic Therapy ◽  
Failure Rates ◽  
Prostate Biopsies ◽  
Psa Failure

PURPOSE: Prostate-specific antigen (PSA) failure within 2 years after radical prostatectomy (RP) has been shown to be a clinically significant predictor of distant failure. This study was performed to estimate 2-year PSA failure rates on the basis of readily available clinical and pathologic factors to identify patients for whom effective adjuvant systemic therapy is needed. PATIENTS AND METHODS: A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies, PSA level, and the pathologic findings at RP in 1,728 men provided clinically relevant information about PSA outcome after RP. A bootstrapping technique with 2,000 replications was used to provide 95% confidence intervals for the predicted 2-year PSA failure rates, which were determined on the basis of the independent clinical and pathologic predictors of PSA outcome. RESULTS: The independent predictors of time to PSA failure included a percentage of positive prostate biopsies of greater than 34% (P ≤ .009), PSA level greater than 10 ng/mL (P ≤ .01), seminal vesicle invasion (P = .02), prostatectomy Gleason score of 8 to 10 (P = .04), and positive surgical margins (P = .0001). Predictions of 2-year PSA failure rates and bootstrap estimates of the 95% confidence intervals were arranged in a tabular format, stratified by independent clinical and pathologic predictors of PSA outcome. CONCLUSION: Patients who are most likely to benefit from effective adjuvant systemic therapy after RP can be identified using readily available clinical and pathologic data.

Six-Month Androgen Suppression Plus Radiation Therapy Compared With Radiation Therapy Alone for Men With Prostate Cancer and a Rapidly Increasing Pretreatment Prostate-Specific Antigen Level

2006 ◽  
Vol 24 (25) ◽  
pp. 4190-4195 ◽  
Author(s):  
Anthony V. D'Amico ◽  
Marian Loffredo ◽  
Andrew A. Renshaw ◽  
Brittany Loffredo ◽  
Ming-Hui Chen
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Prostate Specific Antigen ◽  
Cox Regression ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Study Cohort ◽  
Psa Recurrence ◽  
Psa Velocity ◽  
Androgen Suppression

PurposeWe evaluated whether treatment with 6 months of androgen-suppression therapy (AST) and radiation therapy (RT) compared with RT was associated with the time to prostate-specific antigen (PSA) recurrence, prostate cancer–specific mortality (PCSM), and all-cause mortality (ACM) in men with a pretreatment PSA velocity more than 2 ng/mL/yr.Patients and MethodsThe study cohort comprised 241 men with clinically localized or locally advanced prostate cancer treated with RT and AST or RT from 1989 to 2002. Cox regression and Gray's formulation were used to assess whether treatment was associated significantly with the time to PSA recurrence or ACM and PCSM, respectively, adjusting for known prognostic factors.ResultsDespite the significantly longer median follow-up, younger age at diagnosis, higher proportion of Gleason score 7 to 10, and advanced T-category cancers, significantly lower estimates of PSA recurrence (P < .001), PCSM (P = .007), and ACM (P < .001) were observed in men who were treated using RT and AST compared with RT. Treatment with RT and AST compared with RT was associated with a longer time to PSA recurrence (adjusted hazard ratio [HR], 0.22; 95% CI, 0.14 to 0.35; P < .001), PCSM (HR, 0.23, 95% CI, 0.09 to 0.64; P = .005), and ACM (HR, 0.30; 95% CI, 0.16 to 0.58; P < .001).ConclusionTreatment using 6 months of AST and RT compared with RT in men with a pretreatment PSA velocity greater than 2 ng/mL/yr was associated with a longer time to PSA recurrence, PCSM, and ACM.

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