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.

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.

National trends in the management of patients with positive surgical margins at the time of radical prostatectomy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 111-111 ◽  
Author(s):  
Kamyar Ghabili ◽  
Kevin Nguyen ◽  
Walter Hsiang ◽  
Jamil Syed ◽  
Alfredo Suarez-Sarmiento ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Adjuvant Therapy ◽  
Multivariable Analysis ◽  
Surgical Margins ◽  
Definitive Treatment ◽  
Management Approach ◽  
Adjuvant Radiation ◽  
Gleason Grade ◽  
Positive Surgical Margins ◽  
Pathologic Features

111 Background: The optimal management approach for patients with positive surgical margins (PSM) at radical prostatectomy (RP) has not been definitively assessed. To better understand contemporary patterns of care, we sought to examine time trends and determinants of adjuvant therapy in a large national sample of men with prostate cancer (PCa) treated with RP. Methods: We queried the National Cancer Database (NCDB) to identify men with clinically-localized PCa diagnosed from 2010 to 2014 who had PSM at RP performed as initial primary definitive treatment. We used descriptive statistics to examine subsequent management strategies, assessed as no adjuvant therapy as part of the initial planned course of management, receipt of adjuvant radiation therapy (RT), and receipt of adjuvant RT in combination with androgen deprivation therapy (ADT). Binary logistic regression models were constructed to identify patient, tumor, and facility features associated with receipt of adjuvant therapy. Results: During the study period, we identified 44,523 patients with PSM. Of those, 5,179 (11.6%) men received any adjuvant RT (+/- ADT), while only 1,380 (3%) received adjuvant RT with ADT. Use of adjuvant RT did not change over the study period ( p= 0.61). On multivariable analysis men of uninsured status (p = 0.003), Medicaid insurance (p = 0.001), and patients treated in non-academic facilities (p < 0.001) were more likely to receive adjuvant RT. In addition, use of adjuvant RT was associated with higher pre-treatment PSA (p < 0.001), pathologic stage (p < 0.001) and Gleason grade group (p < 0.001), decreasing distance from the treatment center (p < 0.001), and shorter duration between diagnosis and RP (p < 0.001). Receipt of adjuvant ADT with RT was associated with clinical and pathologic features; however, not with sociodemographic factors. Conclusions: The majority of patients experiencing PSM at RP did not receive adjuvant RT, and rates of adjuvant therapy have remained stable over time. In addition to adverse clinical and pathologic features, sociodemographic and facility factors were significantly associated with receipt of adjuvant RT; however, the addition of ADT appears largely driven by disease characteristics.

Hemorrhagic and Cystic Brain Metastases Are Associated With an Increased Risk of Leptomeningeal Dissemination After Surgical Resection and Adjuvant Stereotactic Radiosurgery

Neurosurgery ◽  
2018 ◽  
Vol 85 (5) ◽  
pp. 632-641 ◽  
Author(s):  
Robert H Press ◽  
Chao Zhang ◽  
Mudit Chowdhary ◽  
Roshan S Prabhu ◽  
Matthew J Ferris ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Surgical Resection ◽  
Cumulative Incidence ◽  
Postoperative Radiotherapy ◽  
Multivariable Analysis ◽  
Treatment Strategies ◽  
Competing Risk ◽  
Leptomeningeal Dissemination ◽  
Increased Risk

Abstract BACKGROUND Brain metastases (BM) treated with surgical resection and focal postoperative radiotherapy have been associated with an increased risk of subsequent leptomeningeal dissemination (LMD). BMs with hemorrhagic and/or cystic features contain less solid components and may therefore be at higher risk for tumor spillage during resection. OBJECTIVE To investigate the association between hemorrhagic and cystic BMs treated with surgical resection and stereotactic radiosurgery and the risk of LMD. METHODS One hundred thirty-four consecutive patients with a single resected BM treated with adjuvant stereotactic radiosurgery from 2008 to 2016 were identified. Intracranial outcomes including LMD were calculated using the cumulative incidence model with death as a competing risk. Univariable analysis and multivariable analysis were assessed using the Fine & Gray model. Overall survival was analyzed using the Kaplan-Meier method. RESULTS Median imaging follow-up was 14.2 mo (range 2.5-132 mo). Hemorrhagic and cystic features were present in 46 (34%) and 32 (24%) patients, respectively. The overall 12- and 24-mo cumulative incidence of LMD with death as a competing risk was 11.0 and 22.4%, respectively. On multivariable analysis, hemorrhagic features (hazard ratio [HR] 2.34, P = .015), cystic features (HR 2.34, P = .013), breast histology (HR 3.23, P = .016), and number of brain metastases >1 (HR 2.09, P = .032) were independently associated with increased risk of LMD. CONCLUSION Hemorrhagic and cystic features were independently associated with increased risk for postoperative LMD. Patients with BMs containing these intralesion features may benefit from alternative treatment strategies to mitigate this risk.

scholarly journals Observation with or without late radiotherapy is equivalent to early radiotherapy in high-risk prostate cancer after radical prostatectomy: A SEER-Medicare analysis on trends, survival outcomes and complications

2019 ◽  
Author(s):  
Young Suk Suk Kwon ◽  
Wei Wang ◽  
Arnav Srivast ◽  
Thomas L Jang ◽  
Singer A Eric ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Cox Regression ◽  
Survival Outcomes ◽  
Study Cohort ◽  
High Risk Prostate Cancer ◽  
Pathologic Features ◽  
Risk Prostate Cancer

Abstract Introduction: While early radiotherapy (eRT) after radical prostatectomy (RP) has shown to improve oncologic outcomes in patients with high-risk prostate cancer (PCa) in a recent clinical trial, controversy remains regarding its benefit. We aimed to illustrate national trends of post-RP radiotherapy and compare outcomes and toxicities in patients receiving eRT vs. observation with or without late radiotherapy (lRT). Methods: Utilizing the Surveillance, Epidemiology and End Results (SEER)-Medicare data from 2001 to 2011, we identified 7557 patients with high-risk pathologic features after RP (≥ pT3N0 and/or positive surgical margins). Our study cohort was consisted of patients receiving RT within 6 months of surgery (eRT), those receiving RT after 6 months (IRT), and those never receiving RT (observation). Another subcohort, delayed RT (dRT), encompassed both IRT and observation. Trends of post-RP radiotherapy were compared using the Cochran-Armitage trend test. Cox regression models identified factors predictive of worse survival outcomes. Kaplan-Meier analyses compared the eRT and the dRT groups. Results: Among those with pathologically confirmed high-risk PCa after RP, 12.7% (n=959), 13.2% (n=1710), and 74.1% (n=4888) underwent eRT, lRT, and observation without RT, respectively. Of these strategies, the proportion of men on observation without RT increased significantly over time (p=0.004). Multivariable Cox regression model demonstrated similar outcomes between the eRT and the dRT groups. At a median follow up of 5.9 years, five-year overall and cancer-specific survival outcomes were more favorable in the dRT group, when compared to the eRT group. Radiation related toxicities, including urinary incontinence, erectile dysfunction, and urethral stricture, were higher in the eRT group when compared to the lRT group. Conclusions: Our results suggest that a blanket adoption of the eRT in high-risk PCa based on clinical trials with limited follow up may result in overtreatment of a significant number of men and expose them to unnecessary radiation toxicity.

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]

Can PSA testing stop 10 years after radical prostatectomy?

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 179-179
Author(s):  
S. Loeb ◽  
Z. Feng ◽  
A. Ross ◽  
B. J. Trock ◽  
E. B. Humphreys ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Cancer Specific Survival ◽  
Psa Testing ◽  
Pathologic Features ◽  
Specific Mortality ◽  
Cancer Specific Mortality ◽  
Multivariable Models ◽  
The Relationship ◽  
Subsequent Risk

179 Background: Biochemical recurrence (BCR) most frequently occurs within the first five years following radical prostatectomy. Prior studies have suggested an association between lower-risk disease features and BCR at 5 years postoperatively. The objective of our study was to determine predictors of BCR ≥10 years after radical prostatectomy, and to examine the relationship between timing of BCR with the subsequent risk of metastases and cancer-specific mortality. Methods: Among 10,609 men from our institutional radical prostatectomy database, we identified 1684 men with BCR (PSA >0.2 ng/ml) without prior hormonal or radiation therapy. These men were classified into by the time of BCR: early (<5 years), intermediate (5-10 years), and late (>10 years). Univariable and multivariable models were used to examine the association of clinico-pathologic variables with the timing of BCR. We also examined metastasis-free and cancer-specific survival based upon the timing of BCR. Results: Of BCR, 77.0%, 16.6%, 4.9%, and 1.5% occurred at <5, 5-10, 10-15, and >15 years postoperatively. Late recurrences were associated with more favorable pathologic features, and were unlikely to develop metastases or prostate cancer-specific mortality. Conclusions: The majority of BCR occurs within 10 years of surgery. Although 6.4% of BCR occurred at ≥10 years, these patients were unlikely to subsequently develop metastases or die from prostate cancer. Patients who remain free from progression at 10 years postoperatively should be counseled that their risk of subsequent cancer-related morbidity and mortality is low. No significant financial relationships to disclose.

The impact of race on adverse pathologic features at the time of radical prostatectomy in men with prostate cancer and implications for adjuvant radiotherapy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 75-75
Author(s):  
Gregory Arthur Jordan ◽  
Richa Bhasin ◽  
Alec Block ◽  
Alex Gorbonos ◽  
Marcus Lee Quek ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Black Men ◽  
Adjuvant Radiotherapy ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Positive Margins ◽  
Advanced Tumor ◽  
Pathologic Features ◽  
The Impact

75 Background: Patients with adverse pathologic features (≥pT3 disease or positive margins) at the time of radical prostatectomy (RP) have higher biochemical recurrence (BR). Adjuvant radiotherapy (ART) reduces BR, but has potential toxicities. Also, studies suggest Black men are more likely to have aggressive prostate cancer. Our objective was to identify whether black men undergoing RP are more likely to have adverse pathologic features (APF) that lead to an indication for ART. Methods: We conducted a retrospective cohort study of men with cT1-4 Nx/0 Mx/0 prostate adenocarcinoma in the National Cancer Database who underwent RP. Race was divided into 3 groups (Caucasian, Black, Other). Chi-square tests and analysis of variance (ANOVA) tests were used to compare clinical and socioeconomic covariates between race groups. Univariate (UVA) and multivariable analysis (MVA) were performed using logistic regression (LR) to identify covariates predicting for APF. LR was performed to identify the impact of race on pT3 disease and positive margins. Results: A total of 313,013 patients diagnosed between 2004-2014 and undergoing RP were included. 256,315 (85%) were Caucasian, 33,725 (11%) were Black, and 12,973 (4%) were Other race. Fewer Black men had Gleason group 1 (33% vs. 41%) but more had Gleason group 2 disease (46% vs. 38%, p < 0.001). Black men more frequently had PSA ≥10 ng/ml (18% vs. 16%, p < 0.001) and ≥cT2b disease (18% vs. 14%, p < 0.001). On UVA, Black men were more likely to have APF (Odds Ratio [OR] 1.18; 95% Confidence Interval [CI] 1.15-1.21; [p < 0.001]). On MVA, black race was independently associated with having APF (OR 1.21; 95% CI 1.18-1.24; p < 0.001). Black men were more likely to have positive margins (OR 1.26; 95% CI 1.22-1.29; p < 0.001) but less likely to have ≥pT3 disease (OR 0.77; 95% CI 0.74-0.79; p < 0.001). Conclusions: Independent of socioeconomic and clinical factors, Black men undergoing RP are more likely to have APF, increasing the risk of BR in this group, and more frequently creating an indication for ART. This appears to be more due to positive margins than locally advanced tumor. The underlying cause of this disparity warrants further exploration.

scholarly journals Outcomes and Prediction Models for Exclusive Prostate Bed Salvage Radiotherapy among Patients with Biochemical Recurrence after Radical Prostatectomy

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2672
Author(s):  
Chi-Shin Tseng ◽  
Yu-Jen Wang ◽  
Chung-Hsin Chen ◽  
Shuo-Meng Wang ◽  
Kuo-How Huang ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Biochemical Recurrence ◽  
Prediction Models ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Salvage Radiotherapy ◽  
Free Survival ◽  
Prostate Bed ◽  
Kaplan Meier ◽  
Observational Cohort

Background: The addition of androgen-deprivation therapy (ADT) or pelvic radiation to prostate bed salvage radiotherapy (SRT) has been debated for prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy. This study aimed to assess the outcomes and propose prediction models for exclusive prostate bed SRT. Methods: This is a prospective observational cohort study with patients who underwent SRT with a pre-SRT PSA < 1.5 ng/mL after radical prostatectomy. Patients were treated with 70-Gy SRT to the prostate bed exclusively. Kaplan–Meier survival analyses and Cox regression analyses were applied for depicting and predicting BCR-free survival, ADT-free survival, and metastasis-free survival (MFS). Regression-based coefficients were used to develop nomograms. Results: A total of 105 patients were included and 91 patients were eligible. The median follow-up period was 39 months. The 5-year BCR-free survival, ADT-free survival, and MFS were 37%, 50%, and 66%, respectively. Multivariable analysis showed that a pre-SRT PSA < 0.45 ng/mL was the only independent factor associated with longer BCR-free survival (p = 0.034), while a PSA-DT > 8 months had better ADT-free survival (p = 0.008). Patients with a PSA-DT > 8 months showed a 100% MFS and a 43% 5-year absolute benefit in MFS than a PSA-DT ≤ 8 months. All patients with a pre-SRT PSA < 0.45 ng/mL and PSA-DT > 8 months were free from subsequent ADT and any metastasis. Conclusions: In patients with a PSA < 0.45 ng/mL and PSA-DT > 8 months for post-prostatectomy BCR, prostate bed SRT provided excellent outcomes without the need for concomitant ADT or pelvic radiotherapy.

scholarly journals Predictive Factors and Oncologic Outcome of Downgrade to Pathologic Gleason Score 6–7 after Radical Prostatectomy in Patients with Biopsy Gleason Score 8–10

2019 ◽  
Vol 8 (4) ◽  
pp. 438 ◽  
Author(s):  
Doo Chung ◽  
Jong Lee ◽  
Hyeok Goh ◽  
Dong Koh ◽  
Min Kim ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Predictive Factors ◽  
Cox Regression ◽  
Specific Antigen ◽  
Surgical Margin ◽  
Positive Surgical Margin ◽  
Cox Regression Analysis ◽  
Pathologic Features

Gleason score (GS) 8–10 is associated with adverse outcomes in prostate cancer (PCa). However, biopsy GS (bGS) may be upgraded or downgraded post-radical prostatectomy (RP). We aimed to investigate predictive factors and oncologic outcomes of downgrade to pathologic GS (pGS) 6–7 after RP in PCa patients with bGSs 8–10. We retrospectively reviewed clinical data of patients with bGS ≥ 8 undergoing RP. pGS downgrade was defined as a pGS ≤ 7 from bGS ≥ 8 post-RP. Univariate and multivariate cox regression analysis, logistic regression analysis, and Kaplan–Meier curves were used to analyze pGS downgrade and biochemical recurrence (BCR). Of 860 patients, 623 and 237 had bGS 8 and bGS ≥ 9, respectively. Post-RP, 332 patients were downgraded to pGS ≤ 7; of these, 284 and 48 had bGS 8 and bGS ≥ 9, respectively. Prostate-specific antigen (PSA) levels; clinical stage; and adverse pathologic features such as extracapsular extension, seminal vesicle invasion and positive surgical margin were significantly different between patients with pGS ≤ 7 and pGS ≥ 8. Furthermore, bGS 8 (odds ratio (OR): 0.349, p < 0.001), PSA level < 10 ng/mL (OR: 0.634, p = 0.004), and ≤cT3a (OR: 0.400, p < 0.001) were identified as significant predictors of pGS downgrade. pGS downgrade was a significant positive predictor of BCR following RP in patients with high bGS (vs. pGS 8, hazard radio (HR): 1.699, p < 0.001; vs. pGS ≥ 9, HR: 1.765, p < 0.001). In addition, the 5-year BCR-free survival rate in patients with pGS downgrade significantly differed from that in patients with bGS 8 and ≥ 9 (52.9% vs. 40.7%, p < 0.001). Among patients with bGS ≥ 8, those with bGS 8, PSA level < 10 ng/mL, and ≤cT3a may achieve pGS downgrade after RP. These patients may have fewer adverse pathologic features and show a favorable prognosis; thus we suggest that active treatment is needed in these patients. In addition, patients with high-grade bGS should be managed aggressively, even if they show pGS downgrade.

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