PE25: Paradoxical lower positive margin rates seen in patients with D’Amico high risk prostate cancer compared to low/intermediate risk patients in robotic prostatectomy series

14641 Objective: To evaluate the value of neoadjuvant (NHT) and concomitant hormonal therapy (CHT) for high risk prostate cancer patients treated with conformal radiotherapy (3DCRT). Methods: From October 1997 to January 2002, 116 patients with high risk prostate cancer were submitted to 3DCRT and were analyzed retrospectively. High risk patients were defined as patients with PSA >20 ng/ml, and/or T3 clinical stage and/or Gleason score >7, or two factors of intermediate risk (PSA ≥10 and <20 ng/ml, T2b-T2c and Gleason score >7). The NHT and CHT were performed on 69 (59.5%) and 79 (68.1%) patients, respectively. The prostate and seminal vesicles median doses were 81 Gy (72–82.8) and 61.2 Gy (45–77.4) respectively. The median time from diagnosis to 3DCRT was 2,9 months (0.9–134.9). Results: On median follow-up of 54.5 months (13.5–93.9), the 5-year actuarial overall (OS) and 5-year biochemical progression-free survival (BPFS) were 84.3% and 64.7% respectively. The OS for patients submitted to NHT was 89.8% versus 76.4% for patients that were not submitted to (p = 0.0139). Patients that received CHT had an OS of 89.6% versus 73.4% for patients that did not receive CHT (p = 0.0201). Gleason score, clinical stage and seminal vesicles irradiation were significant to BPFS (p = 0.0372, p = 0.0412 and p = 0.0321 respectively). Conclusions: NHT and CHT increased OS of high risk prostate cancer of patients. Gleason score and clinical stage were important prognostic factors to BPFS. Seminal vesicles irradiation is recommended for high risk patients. No significant financial relationships to disclose.

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A matched-pair analysis of dose-escalated adaptive image-guided radiotherapy (IGRT) versus pelvic irradiation with brachytherapy boost for intermediate- and high-risk prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.71 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 71-71

Author(s):

C. Shah ◽

L. L. Kestin ◽

M. Ghilezan ◽

F. A. Vicini ◽

G. S. Gustafson ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Clinical Outcomes ◽

Matched Pair ◽

High Dose ◽

High Risk Prostate Cancer ◽

Matched Pair Analysis ◽

Risk Prostate Cancer ◽

Brachytherapy Boost ◽

Risk Patients

71 Background: The purpose of this study was to compare clinical outcomes in a cohort of intermediate- and high-risk prostate cancer patients treated with either dose-escalated adaptive IGRT or pelvic external beam RT with high-dose rate brachytherapy boost (EBRT+HDR). Methods: 1,520 patients with clinical stage T1-T3 N0 M0 prostate cancer were treated with either CT-based offline adaptive IGRT (n=1,037) or EBRT+HDR, n=438) at William Beaumont Hospital. For IGRT, the CTV included the prostate and proximal seminal vesicles only. Median dose (minimum to cl-PTV) delivered via 3D conformal RT or intensity-modulated RT was 75.6 Gy (range: 73.8-79.2 Gy). For EBRT+HDR, the whole pelvis was treated to 46 Gy + 2 HDR implants with a median of 10.5 Gy (8.75-11.5 Gy) per implant. 208 patients from each group were matched based on criteria of pretreatment PSA ± 4 ng/mL, same Gleason score, T stage ± 2 sublevels, and use of neoadjuvant androgen deprivation therapy (ADT). Results: Mean follow-up was 5.1 years for IGRT vs 7.0 years for EBRT+HDR. Mean pretreatment PSA was 9 for both groups. Mean Gleason was 7 for both groups. EBRT+HDR patients were younger (67 vs 71 years, p<0.01) with a higher percentage of positive biopsy cores (51% vs 39%, p<0.01). Intermediate risk patients comprised 78% and 76% for IGRT and EBRT+HDR, respectively (p=0.56). 42% in each treatment group received neoadjuvant or concurrent ADT. 5-year biochemical control (BC) based on the Phoenix definition was 91% for IGRT vs 87% for EBRT+HDR (p=0.60). For intermediate-risk, 5-year BC was 94% vs 87% (p=0.71) and was 86% vs 86% (p=0.83) for high-risk patients. No significant differences were noted between the 2 groups for local recurrence, distant metastasis, clinical failure, overall survival, and cause-specific survival. Conclusions: In this matched-pair analysis of 416 patients, treatment of intermediate and high-risk prostate cancer with either offline adaptive IGRT or EBRT+HDR yielded excellent clinical outcomes without significant differences. The omission of pelvic radiotherapy in the IGRT patients did not appear to be associated with poorer clinical outcomes with modern high-dose RT. No significant financial relationships to disclose.

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Impact of different definitions of high-risk prostate cancer on survival after radical prostatectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.113 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 113-113

Author(s):

Kenneth Gerard Nepple ◽

Gurdarshan S Sandhu ◽

Dorina Kallogjeri ◽

Seth A. Strope ◽

Robert L. Grubb ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Radical Prostatectomy ◽

Cancer Survival ◽

Clinical Stage ◽

High Risk Patients ◽

High Risk Prostate Cancer ◽

Increased Risk ◽

Risk Prostate Cancer ◽

Risk Patients

113 Background: Multiple definitions of high risk prostate cancer exist. Studies have primarily correlated these definitions with biochemical recurrence and not with survival. We applied six previously described high risk definitions to men treated with radical prostatectomy and evaluated their ability to predict survival outcomes in a multi-institutional cohort. Methods: The study population included 6477 men treated with radical prostatectomy between 1995 and 2005 and followed for a median of 67 months. The six high risk definitions were 1) preoperative PSA≥20ng/ml, 2) biopsy Gleason score 8-10, 3) clinical stage≥T2c, 4) clinical stage T3, 5) D’Amico definition, or 6) National Comprehensive Cancer Network definition. Survival was evaluated with the Kaplan-Meier method to generate unadjusted prostate cancer survival estimates. To control for the competing risks of age and comorbidity, multivariable Cox proportional hazard regression models were used to estimate the hazard ratio for prostate cancer specific mortality (PCSM) and overall mortality (OM) in high risk patients compared to low/intermediate risk. Results: High risk patients comprised between 0.7% (cT3) and 8.2% (D’Amico) of the study population. The 10-year Kaplan Meier prostate cancer survival estimates varied from 89.7% for PSA≥20 to 69.7% for cT3. On multivariable analysis controlling for age and comorbidity, high risk prostate cancer (of all definitions) had an increased risk of PCSM compared to low/intermediate risk with a hazard ratio (HR) ranging from 4.38 for PSA≥20 to 19.97 for cT3 (all p<0.0001). For OM, again controlling for age and comorbidity, high risk patients of all definitions except preoperative PSA≥20 (HR=0.98, p=0.99) were associated with increased risk of OM (HR range: 1.72 for D’Amico, 1.73 for stage≥T2c, 1.88 for NCCN, 2.63 for Gleason 8-10, 3.31 for cT3; all p<0.01). Conclusions: In a contemporary cohort of men with high risk prostate cancer treated with radical prostatectomy, the majority of men experienced long term prostate cancer survival. However, heterogeneity in survival outcomes existed based on the definition of high risk used. Clinical stage T3 and high Gleason score were most strongly associated with PCSM and OM.

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Does race affect the quality of treatment for intermediate-risk and high-risk prostate cancer?

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.e17678 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. e17678-e17678

Author(s):

Nina A. Bickell ◽

Simon J Hall ◽

Richard Stock ◽

Kezhen Fei ◽

Rajwanth Veluswamy ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Intermediate Risk ◽

Quality Of Treatment ◽

High Risk Prostate Cancer ◽

Risk Prostate Cancer

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Comorbidity and androgen deprivation therapy use in men undergoing high-dose radiation for unfavorable intermediate- and high-risk prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.41 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 41-41

Author(s):

Michael A Dyer ◽

Ming-Hui Chen ◽

Michelle H. Braccioforte ◽

Brian Joseph Moran ◽

Anthony V. D'Amico

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

External Beam Radiation ◽

Intermediate Risk ◽

High Risk Prostate Cancer ◽

Risk Prostate Cancer ◽

History Of ◽

Over Time

41 Background: Despite evidence of prolonged survival when adding androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) in men with unfavorable intermediate- and high-risk prostate cancer (PC), some of these men are not receiving ADT. We explored whether comorbidity can explain this discrepancy given the observation that survival may be shortened in men with moderate to severe comorbidity who receive ADT. Methods: Between 10/1997 and 5/2013, 3,348 men with unfavorable intermediate- (2,380 patients; 70.7%) or high-risk (986 patients; 29.3%) PC were treated at the Prostate Cancer Foundation of Chicago using brachytherapy with or without neoadjuvant EBRT and/or ADT, and formed the study cohort. A multivariable logistic regression analysis was used to evaluate whether comorbidity (history of congestive heart failure [CHF] and/or myocardial infarction [MI]) was associated with decreased odds of ADT use in men with unfavorable intermediate- or high-risk PC, adjusting for age, PC prognostic factors, year of brachytherapy, and EBRT use. Results: Among patients with unfavorable-intermediate-risk PC, 31.2% received ADT, and in the high-risk cohort, 38.3%, 12.3%, and 4.8% received up to 6, >6-18, or >18 months of ADT respectively. In men with high-risk PC, a history of CHF/MI was not significantly associated with decreased odds of ADT use of any duration (all p values >0.71), but the odds of ADT use decreased over time (adjusted odds ratio (AOR) 0.87, 95% confidence interval (CI) [0.83,0.91], p<0.0001; AOR 0.93, 95% CI [0.87,0.99], p=0.023; AOR 0.92, 95% CI [0.83,1.01], p=0.089, for up to 6, >6-18, and >18 months respectively, with no ADT as the reference). Similarly, in men with unfavorable intermediate-risk PC, a history of CHF/MI was not significantly associated with decreased odds of ADT use (p=0.49), whereas the odds of ADT use decreased significantly over time (AOR 0.96, 95% CI [0.94,0.98], p=0.0009). Conclusions: While ADT use has decreased over time in men with unfavorable intermediate- and high-risk PC undergoing brachytherapy with or without supplemental EBRT, this decrease does not appear to be occurring in men with a history of CHF or MI.

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Clinical-genomic sub-classification of high-risk prostate cancer: Implications for tailoring therapy and clinical trial design.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.337 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 337-337

Author(s):

Vinayak Muralidhar ◽

Mohammed Alshalalfa ◽

Daniel Eidelberg Spratt ◽

Yang Liu ◽

R. Jeffrey Karnes ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Risk Stratification ◽

High Risk Prostate Cancer ◽

High Risk Disease ◽

Risk Prostate Cancer ◽

Risk Patients ◽

Genomic Risk ◽

Clinical Genomic ◽

Very High

337 Background: Current risk stratification schema have limited prognostic performance in predicting outcome within National Comprehensive Cancer Network (NCCN) high-risk to very high-risk prostate cancer. Methods: Two multicenter high-risk cohorts were used for training (n = 214) and validation (n = 151) of a novel RNA microarray-based integrated clinical-genomic Classifier Optimized for Outcome in High-risk Prostate cancer (COOHP) to classify patients as COOHP favorable high-risk, standard high-risk, or very high-risk. Cox analysis was used to model metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Model performance was compared to prior sub-classification systems using time-dependent c-indices. Results: Among NCCN high/very high-risk patients in the training cohort, 11% were classified as COOHP favorable high-risk, 70% as COOHP standard high-risk, and 18% as COOHP very high-risk. Patients with COOHP favorable high-risk disease had better rates of 5-year MFS compared to those with COOHP standard high-risk disease (94% vs 76%, hazard ratio [HR] 0.10, p = 0.02), and patients with COOHP very high-risk disease had worse 5-year MFS compared to those with COOHP standard high-risk disease (34% vs 76%, HR 3.5, p < 0.0001). Similarly, patients with COOHP very high-risk disease had worse 10-year PCSS compared to those with COOHP standard high-risk disease (36% vs 82%, HR 4.4, p < 0.0001). The c-indices for 5-year MFS and 10-year PCSS in the training cohort were 0.80 and 0.74, significantly improved compared to prior clinical and clinical-genomic risk stratification systems (0.62-0.69 for 5-year MFS and 0.56-0.63 for 10-year PCSS). These results were consistent in the validation cohort, where 5-year MFS significantly varied among the three COOHP subgroups (100% vs 89% vs 79%, p = 0.020), as did 10-year OS (100% vs 71% vs 53%, p = .040). Conclusions: A clinical-genomic risk stratification system specifically designed to discriminate prognosis in high-risk prostate cancer better identified favorable high-risk and very high-risk subsets of disease compared to prior clinical and clinical-genomic stratification systems.

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