Cell cycle progression score and PTEN as prognostic factors for metastasis in intermediate and high-risk prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16575-e16575
Author(s):  
Bruce J. Trock ◽  
Saradha Rajamani ◽  
Igor Vidal ◽  
Stephanie Glavaris ◽  
Tracy Jones ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
High Risk ◽  
Cell Cycle Progression ◽  
Multivariable Analysis ◽  
Cycle Progression ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Myriad Genetics ◽  
Univariate Analyses

e16575 Background: To evaluate the cell cycle progression (CCP) score and PTEN as prognostic markers for risk of metastasis in a radical prostatectomy (RP) cohort of NCCN intermediate and high risk prostate cancer. Methods: This IRB-approved case-cohort study included men treated with RP at Johns Hopkins from 2007-2015. Paraffin-embedded RP tissue was analyzed blind to study outcome at Myriad Genetics, for CCP score using qRT-PCR, and PTEN by immunohistochemistry. Metastasis-free survival (MFS) was analyzed with the Cox proportional hazards model, weighted for case-cohort design. CCP and PTEN were analyzed independently, and adjusted for CAPRA-S. The CCR score, which combines CCP and CAPRA-S, was also analyzed. Data were analyzed independently by Johns Hopkins and Myriad Genetics. Results: There were 209 patients, of whom 42 were cases (metastasis). Median age was 59 years, 47% had Gleason 4+3 or higher, 48% had non-organ confined tumor, and 18% had seminal vesicle or lymph node involvement. NCCN risk was intermediate in 77% and high in 23%. Median follow-up was 4 years. Both CCP and PTEN, as well as CCR score, were statistically significant in univariate analyses, but only CCP retained statistical significance in a multivariable model of CCP, PTEN, and CAPRA-S (Table). Conclusions: This is the first comparison of the CCP score and PTEN as risk factors for metastasis in a recent RP cohort of patients at NCCN intermediate or high risk. Both CCP score and PTEN were strongly associated with MFS in univariate analyses, but only CCP score retained significance in a multivariable analysis with both biomarkers adjusted for CAPRA-S. [Table: see text]

Cell cycle progression score and PTEN as prognostic factors for metastasis in intermediate- and high-risk prostate cancer overall, and in those who also received salvage radiotherapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 247-247
Author(s):  
Bruce J. Trock ◽  
Saradha Rajamani ◽  
Igor Vidal ◽  
Stephanie Glavaris ◽  
Tracy Jones ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
High Risk ◽  
Cell Cycle Progression ◽  
Lymph Node Involvement ◽  
Cycle Progression ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Myriad Genetics ◽  
Node Involvement

247 Background: The cell cycle progression (CCP) score and PTEN have never been evaluated together as prognostic markers for risk of metastasis in a radical prostatectomy (RP) cohort of men with National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa), nor in such patients who also received salvage radiation (SRT) alone or with androgen deprivation (SRT+ADT). This study evaluated CCP score and PTEN in both settings. Methods: Participants were treated with RP at Johns Hopkins from 2007-2015. Paraffin-embedded RP tissue was analyzed blind to clinical outcome at Myriad Genetics, for CCP score using qRT-PCR, and PTEN by immunohistochemistry. For overall evaluation of CCP and PTEN in intermediate- and high-risk men a case-cohort sample was selected. Intermediate- and high-risk men with biochemical recurrence who received SRT or SRT+ADT were also sampled to provide a population at particularly high risk. Metastasis-free survival (MFS) was analyzed with the proportional hazards model, weighted for case-cohort design for the overall analysis, and adjusted for CAPRA-S. The clinical cell-cycle risk (CCR) score, a fixed algorithm combining CCP and CAPRA-S was also analyzed in both contexts. Data were analyzed independently by Johns Hopkins and Myriad Genetics. Results: The case-cohort consisted of 209 men, including 47% with Gleason score >4+3, 48% extra-prostatic extension, and 18% with seminal vesicle or lymph node involvement; 42 (20%) developed metastasis. In univariate analyses CCP, CAPRA-S, and PTEN were all highly significant. In multivariable analysis, only CCP and CAPRA-S retained significance (Table section A). CCR was also strongly prognostic, HR=7.9 (95% CI 4.4, 14.5) per unit change, p<0.00001. SRT (56%) or SRT+ADT (44%) were received by 172 men, of whom 78% had Gleason >4+3, 48% extra-prostatic extension, and 34% seminal vesicle or lymph node involvement; 19 (11%) developed metastases. Again, CCP and CAPRA-S, but not PTEN, were statistically significant (Table section B). CCR was also statistically significant, HR=1.7 (95% CI 1.2, 2.4), p=0.002. Conclusions: This is the first comparison, in a recent cohort of intermediate- and high-risk men, of CCP score and PTEN as risk factors for metastasis, and first evaluation in such men receiving SRT. In both multivariable settings, CCP score, but not PTEN, was significantly associated with MFS, adjusted for CAPRA-S. CCR, a fixed algorithm that combines CCP and CAPRA-S was also significant in both settings. [Table: see text]

Ability of the combined clinical cell-cycle risk score to identify patients that benefit from multi versus single modality therapy in NCCN intermediate and high-risk prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 346-346
Author(s):  
Jonathan David Tward ◽  
Thorsten Schlomm ◽  
Stephen Bardot ◽  
Stephen J. Freedland ◽  
Lauren Lenz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
High Risk ◽  
Risk Score ◽  
Cell Cycle Progression ◽  
Full Cohort ◽  
Treatment Benefit ◽  
High Risk Prostate Cancer ◽  
Kaplan Meier ◽  
Risk Prostate Cancer ◽  
The Difference

346 Background: Prolaris combines RNA expression analysis of cell cycle progression genes with clinicopathologic information to create a combined clinical cell-cycle risk score (CCR). We evaluated the ability of CCR to predict metastasis (mets) in men for whom guidelines indicate that multimodality therapy (MTx) should be considered. Methods: A commercial cohort (N=15669) of National Comprehensive Cancer Network unfavorable intermediate-risk (UFI) and high-risk (HR) men revealed a distribution of 70.5% and 29.5% respectively. A CCR threshold of 2.112 was selected so that 29.5% of these men were above the threshold. MTx was defined as combined use of androgen deprivation therapy with radiation (RT) or surgery, or with adjuvant RT. Associations were evaluated in a 718-person retrospective, multi-institutional database of Prolaris-tested UFI and HR men. Kaplan-Meier (KM) analyses and Cox regressions were used to estimate the effects of prognostic covariates. Results: Median follow-up was 5.13 years. CCR predicted mets in the full cohort (HR =3.8 [2.7,5.2], p<10−15) and after accounting for CAPRA (HR=4.3 [2.7,7.0], p< 10−7). CCR also was a significant predictor of mets in patients who received STx, as a continuous predictor (HR=4.0 [2.6,6.1], p<10−9) and when dichotomized at the threshold (HR=15.9 [5.4,46.5], p< 10−9). The KM probability of mets by 10 years for those below and above the threshold was 4.3% and 20.4% respectively. MTx reduced patients’ risk of mets (HR=0.46 [0.22,0.97], p=0.04), and treatment benefit can be evaluated as a function of CCR score (Table). Conclusions: The CCR score prognosticates a clinically meaningful different risk of metastasis for those receiving MTx versus STx. Approximately 27% and 73% of people with HR or UFI risk cancer have CCR scores below the risk threshold and may consider STx after considering the difference in risk of mets.[Table: see text]

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]

Receipt of guideline-concordant treatment in elderly African American and Caucasian patients with prostate cancer.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 222-222 ◽  
Author(s):  
Ronald C. Chen ◽  
William Ruffin Carpenter ◽  
Laura H. Hendrix ◽  
Zhuang Andrew Wang ◽  
Matthew Edward Nielsen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
High Risk ◽  
Elderly Patients ◽  
Cancer Patients ◽  
Multivariable Analysis ◽  
Sociodemographic Factors ◽  
Aggressive Prostate Cancer ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

222 Background: Clinical management of cancer patients according to published guidelines is an important quality indicator. Prior studies have demonstrated less aggressive treatments of elderly patients with breast and colorectal cancers, raising concern about potential undertreatment of elderly patients overall. The rate of guideline concordant management in elderly prostate cancer patients is unknown, and we examined this using the Surveillance, Epidemiologic and End Results (SEER)-Medicare linked database. Given that prostate cancer is often slow growing, we were especially interested in guideline concordance in patients with "high risk" (aggressive) prostate cancer. Methods: 15,154 Caucasian (CA) and 2,924 African American (AA) men diagnosed in 2004 to 2007 with localized prostate cancer, age 66 to 79, were included. We characterized the proportions of men who received management concordant with the National Comprehensive Cancer Network guidelines within 12 months of diagnosis. Logistic regression was used to examine the odds of receiving guideline-concordant management while accounting for race, comorbidity (NCI combined index), SEER region, and sociodemographic factors. Results: Guideline concordance was more than 80% for both CA and AA patients with low- or intermediate-risk disease. Among high-risk patients, only 63% of CA and 48% AA patients received guideline-concordant management, mostly due to no treatment or hormonal therapy alone, which offer no curative potential. Findings were almost identical in the subgroup of patients with little or no comorbidity, who have more than 10 year life expectancy on average. On multivariable analysis, AA race (OR .62, p<.001) and increasing age were associated with lower likelihood of guideline concordance for high-risk prostate cancer, but comorbidity was not. Conclusions: There is undertreatment of elderly but healthy patients with high-risk prostate cancer, the most aggressive form of this disease. Our results suggest a bias toward less aggressive treatment in elderly patients with less consideration for comorbidities or aggressiveness of cancer. Guideline concordance in elderly patients with aggressive prostate cancer is low.

Charlson score to predict overall survival and cancer-related death in elderly patients featuring high-risk prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 84-84
Author(s):  
Guzman Ordaz ◽  
Rafael Sanchez-Salas ◽  
Arjun Sivaraman ◽  
Steven Joniau ◽  
Marco Giorgio Bianchi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Elderly Patients ◽  
Multivariable Analysis ◽  
Treatment Strategies ◽  
Binary Logistic Regression ◽  
High Volume ◽  
Charlson Score ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

84 Background: In elderly patients, Charlson score among other features, might allow clinicians to limit the use of aggressive adjuvant treatment strategies or even primary surgical treatment to those who might not achieve benefit during their lifetime. Methods: Retrospective analysis, 7,650 case multicenter high-risk prostate cancer (Pca) radical prostatectomy database selecting >= 70 years old cases. We predicted death from all causes (DAC) and cancer related death (CRD) including all clinical and pathological data. Multivariable analysis were performed to identify independent predictors of DAC and CRD with binary logistic regression, using STATA® software, version 13.1. Results: 2,106 patients from 14 high-volume centers were included. Mean age was 72.8 years (SD 2.46). 206 (9.78%) patients were classified as ASA 3-4 and 497 (23.6%) as CS >=1. Mean PSA was 21.7 ng/ml (SD 50.5). At final histopathology, 800 (38%) had pT3b-T4 disease, GS was 8-10 in 589 (28%), LNI was found in 518 (24.6%) and 822 (39%) PSM. Adjuvant RT, ADT and RT+ADT were administered in 359 (17%), 391 (18.6%) and 437 (20.7%), respectively. Mean follow up was 5.18 years (DS 4.47). BCR occur in 649 (30.8%) and CF in 150 (7.1%) of which distant in 59 (2.8%). Total deaths accounted 341 (16.2%) and CRD for 100 (4.7%) cases. Conclusions: Multicenter data confirms that elderly patients survival harboring high risk prostate cancer will benefit from radical treatment if they are Charlson score 1 or less. [Table: see text] [Table: see text]

Comparisons of outcomes for patients with high-risk prostate cancer treated with brachytherapy, external beam radiation, or radical prostatectomy.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 63-63
Author(s):  
Jay P. Ciezki ◽  
Harguneet Singh ◽  
Chandana A. Reddy ◽  
Steven C. Campbell ◽  
James Ulchaker ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Multivariable Analysis ◽  
External Beam Radiation ◽  
External Beam ◽  
Beam Radiation ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

63 Background: There is no consensus on how to best treat patients (pts) with high-risk prostate cancer. Methods: The outcomes for 2,736 high-risk prostate cancer pts treated with radical prostatectomy (RP), external beam radiotherapy (RT), and I-125 brachytherapy (BT) at a single institution from 1996 to 2012 were reviewed. The majority of RT pts were treated prior to 2002 because of our preference for RP and BT over time. High-risk was defined per the NCCN criteria. The outcomes assessed were biochemical failure (bF), clinical failure (cF), and prostate cancer mortality (PCM). Results: The distribution by treatment was RP 54%, RT 27%, and BT 19%. The median follow up for all pts was 4.6 years (y) (range 0.1-19.5): 3.8 y (0.1-18.7) for RP, 7.7 y (0.1-19.4) for RT, and 4.1 y (0.1-16.8) for BT pts. No patient received RT+BT, and 44% received androgen deprivation therapy (ADT). On multivariable analysis (see table) RP pts were at higher risk for bF vs. RT; BT pts and RT pts were at higher risk for cF vs. RP; and RT pts were at higher risk for PCM vs. RP. All multivariable analyses were adjusted for clinical stage, biopsy Gleason score, pre-treatment PSA, and duration of ADT. Conclusions: RP is associated with worse bF but better cF and PCM. There is no difference between BT and RT for bF, cF, or PCM while BT and RP had similar PCM. These outcomes may be a result of selection bias or differences in follow up time among the three treatment arms so no demonstration of modality superiority is possible. [Table: see text]

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