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]

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]

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]

18F-choline PET/CT for the assesment of pelvic lymph node metastases in high-risk prostate cancer patients.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 61-61
Author(s):  
Ivan Federico Pinto ◽  
Camilo Sandoval ◽  
Jorge Gonzalo Diaz ◽  
Alvaro Daniel Vidal ◽  
Jaime Antonio Altamirano ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
High Risk ◽  
Lymph Node Involvement ◽  
Pelvic Lymph Node ◽  
Choline Pet ◽  
High Risk Prostate Cancer ◽  
Pet Ct ◽  
Risk Prostate Cancer ◽  
Pelvic Lymph Node Involvement

61 Background: Assesment of pelvic lymph node involvement is a major dilemma due to poor diagnostic accuracy of conventional imaging such as computed tomography of the pelvis or magnetic resonance of the pelvis. Recently incorporation of new tools such as 18F-choline PET/CT address this issue, although there are few studies in this set of patients. To evaluate the 18-choline PET/CT diagnostic accuracy for staging of pelvic lymph node involvement in patients with high risk prostate cancer. Methods: Patients with diagnosis of high risk prostate cancer according to D’Amico risk assessment criteria where staged with a 18F-choline PET/CT prior to treatment with retropubic radical prostatectomy plus superextended bilateral lymph node dissection at our institution. 18F-choline PET/CT was compared with the results of pathological analisys of lymph nodes. We calculated sensitivity, specificity, positive and negative predictive value for 18F-choline PET/CT. Results: Between January 2012 and August 2014 a total of 36 patients met the following inclusion criteria: diagnosis of high prostate cancer (cT2c or more or PSA above 20 ng/ml or a gleason score 8-10), good performance status (ECOG 0-2) and a 18F-choline PET/CT as a preoperative staging procedure. Sensitivity, specificity, positive and negative predictive value were 64%, 92%, 77% and 85% respectively. Conclusions: 18F-choline PET/CT is a non invasive procedure that provides good information regarding pelvic lymph node involvement status that is better than the results of other techniques in published series, with a higher sensitivity in our group of patients. It is highly specific which means there is a very good chance that a patient with a normal study does not have lymph node metastases when analyzed.

Phase II trial of definitive radiotherapy with leuprolide and enzalutamide in high-risk prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 323-323
Author(s):  
Claire Marie de la Calle ◽  
Albert Chang ◽  
Ghezal Rashid ◽  
Anthony C. Wong ◽  
Alice Choi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymph Node Involvement ◽  
Gleason Grade ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Brachytherapy Boost

323 Background: Adding enzalutamide to standard LHRH agonist and primary radiation therapy may improve the outcomes in patients with high-risk prostate cancer. Methods: All patients met at least 2 of the following criteria: stage cT3a/b, PSA≥20 ng/mL, Gleason Grade 8-10, ≥33% core involvement on biopsy; or had pelvic lymph node involvement ≥1cm on CT or MRI. All patients were started on 24 months of leuprolide and enzalutamide and then underwent 5 weeks of IMRT (whole pelvis, 45Gy total) followed by a brachytherapy boost. PSA, Testosterone (T) and basic labs were followed during and after treatment. Primary outcome was to assess the safety, tolerability, and feasibility of the protocol and PSA complete response (PSA-CR, defined as PSA nadir ≤0.3). Secondary outcomes included: time to biochemical recurrence (BCR) and progression free survival (PFS). Results: 16 patients were enrolled, 2 were not eligible and 3 withdrew before starting treatment. Mean age at enrollment was 68.6 years (SD 9.4). Median follow up time was 28.27 months (IQR 27.3 – 29.1 months). Median time to PSA-CR was 4.20 months (IQR 3.47 – 4.87 months). Currently all patients still have PSA-CR (Table), and none have BCR per ASTRO Phoenix criteria. All-cause, any grade adverse events (AE) were reported in all 11 (100%) patients with 4 (36.4%) experiencing grade 3 AE. One (9.09%) treatment related serious AE (seizure) occurred. There were no grade 5 AE (death related to AE). 4 subjects stopped treatment early due to: seizure, myalgias, hematuria and social reasons. Most patients however were able to complete the 24 months of leuprolide and enzalutamide: median treatment duration was 24.0 months (IQR 12.1 – 24.0 months). Conclusions: Most patients were able to tolerate and complete the entire 24 months of treatment as originally planned. Currently no patients have met criteria for PSA recurrence. Will plan to follow up patients until month 36 to help determine true BCR rates and PFS. Clinical trial information: NCT02508636. [Table: see text]

Utility of index lesion volume assessed by multiparametric MRI combined with Gleason grade for assessment of lymph node involvement in patients with high-risk prostate cancer

2019 ◽  
Vol 50 (3) ◽  
pp. 333-337
Author(s):  
Koji Hatano ◽  
Junichiro Tanaka ◽  
Yasutomo Nakai ◽  
Masashi Nakayama ◽  
Ken-ichi Kakimoto ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Lymph Node Involvement ◽  
Lesion Volume ◽  
Gleason Grade ◽  
Index Lesion ◽  
Grade Group ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Node Involvement

Abstract Purpose We examined the potential predictors of lymph node involvement and evaluated whether index lesion volume assessed using multiparametric magnetic resonance imaging is associated with lymph node involvement among patients with high-risk prostate cancer. Methods Extended pelvic lymph node dissection was used to evaluate patients with lymph node involvement. We retrospectively analyzed consecutive 102 patients with high-risk prostate cancer who underwent extended pelvic lymph node dissection at our institution between 2011 and 2017. To evaluate the index lesion volume at multiparametric magnetic resonance imaging (mrV), lesions were manually contoured on each T2-weighted axial slice in combination with diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging and integrated using image analysis software. Logistic regression analysis was performed to identify predictors of lymph node involvement. Results The median mrV was 1.4 ml (range 0–30.1 ml), and the median number of resected lymph nodes was 14 (range 7–38). Among 102 patients, 28 (28%) had lymph node involvement. Multivariate analysis identified significant predictors of lymph node involvement as follows: biopsy Gleason-grade group 5 (odds ratio = 17.2; 95% confidence interval, 2.1–299.0; P = 0.005), preoperative mrV (odds ratio = 1.14; 95% confidence interval, 1.02–1.30; P = 0.025) and percentage of positive cores with highest Gleason-grade group (odds ratio = 1.05; 95% confidence interval, 1.01–1.10; P = 0.005). Lymph node involvement was prevalent (69%) among tumors with Gleason-grade group 5 and mrV ≥3.4 ml, but was infrequently (10%) present among tumors with Gleason-grade group ≤4 and mrV &lt;3.4 ml. Conclusions The combination of biopsy Gleason-grade and mrV may serve as a useful tool to stratify patients according to their risk of nodal metastases.

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