A biopsy-based genomic classifier to predict biochemical failure after definitive radiation without hormone therapy in a prospective cohort of intermediate risk prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 68-68
Author(s):  
Melvin Chua ◽  
Jure Murgic ◽  
Ali Hosni ◽  
Adriana Salcedo ◽  
Suzanne Kamel-Reid ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Rna Extraction ◽  
Multivariable Analysis ◽  
High Risk Group ◽  
Intermediate Risk ◽  
Image Guided Radiotherapy ◽  
Significant Difference ◽  
Risk Prostate Cancer ◽  
Tumor Involvement

68 Background: Recently, NCCN adopted the Zumsteg-Spratt subclassification to define NCCN favorable and unfavorable intermediate-risk prostate cancer (IR-PCa). NCCN unfavorable disease is recommended to receive combination androgen deprivation therapy (ADT) and radiotherapy. To determine if genomics could help identify a subset who may safely avoid ADT, we evaluated the Decipher genomic classifier (GC) in IR-PCa treated with dose-escalated image-guided radiotherapy (DE-IGRT) alone. Methods: Our cohort comprised of 121 patients with NCCN favorable (N = 49, 40%) and unfavorable (N = 74, 60%) IR-PCa, who received 78 Gy without ADT. Diagnostic needle biopsies with the highest Gleason score (GS) and %tumor involvement were macrodissected for RNA extraction. GC scores were determined from the Decipher prostate cancer classifier assay (GenomeDx Biosciences, San Diego, CA). Primary clinical endpoint was biochemical relapse ([BCR], PSA nadir + 2ng/ml) post-DE-IGRT. We compared association with BCR against known clinicopathologic prognostic indices and the NCCN risk strata. Results: With a median follow up of 7.5y, 24 (19%) patients experienced BCR. Individual clinical indices did not predict BCR-free survival rate (BFS). NCCN risk strata was however associated with a small but significant difference in BFS (5-y 93%, favorable vs 88%, unfavourable, P = 0.046). GC scores stratified 85 (70%), 19 (16%), and 17 (14%) men into low, intermediate, and high risk of recurrence; 5-y BFS were 95%, 89%, and 59%, respectively (P < 0.001). On multivariable analysis, a hazard ratio of 4.71 (95% CI 1.81-12.28, P = 0.0015) for BCR was observed for the GC high risk group compared to low/intermediate; NCCN risk strata and intraductal variant did not achieve significance. Conclusions: In IR-PCa men treated with DE-IGRT monotherapy, Decipher GC was an independent predictor of BCR. While most men in this our cohort were stratified as NCCN unfavorable IR-PCa, the majority were GC low risk with excellent outcomes from DE-IGRT alone. In contrast, a minority with GC high risk had suboptimal outcomes, and may benefit from ADT intensification.

An impact of pelvic MRI (PMRI) to radiotherapy (RT) target volumes definition in prostate cancer patients (pts).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 78-78
Author(s):  
Keren Rouvinov ◽  
Wilmosh Mermershtain ◽  
Olga Beloshicki ◽  
Shmuel Ariad ◽  
Konstantin Lavrenkov
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Evaluation Procedure ◽  
High Dose ◽  
Intermediate Risk ◽  
Group Affiliation ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

78 Background: PMRI is a standard pre-RT evaluation procedure in pts with intermediate and high-risk prostate cancer. We conducted a retrospective study to evaluate an influence of PMRI to delineation of RT clinical target volume (CTV). Methods: Medical records of prostate cancer pts treated with intensity-modulated RT (IMRT) in single institution retrieved and examined retrospectively. Initial risk group affiliation was defined using D'Amico method. PMRI reports of pts with intermediate and high-risk prostate cancer were reviewed and risk group affiliation was re-defined in regards of T- and N-stage. IMRT treatment plans were re-assessed. In regards to PMRI T-stage, extra-capsular extension (ECE) and seminal vesicles invasion (SVI) were included to high-dose CTV. Pelvic lymph nodes (PLN) were planned to treat in all high-risk pts. PLN considered pathological by PMRI were included to separate CTV to receive RT dose higher than unaffected PLN stations. Results: Between 2008 and 2014, 169 pts with intermediate and high-risk prostate cancer underwent PMRI at around 1 month before commencing IMRT. Initially, 89 pts were affiliated to intermediate-risk and 80 to high-risk group. In general, PTV-changes based on PMRI data required in 77 pts (45.5%). Thirty seven of 89 intermediate-risk pts (41.6%) have been switched to high-risk group, necessitating irradiation of PLN. ECE and SVI were included to high-dose CTV in 64 (37.8%) and 29 pts (17.2%) respectively. PLN were thought pathological in 10 pts (5.9%), which demanded contouring of a separate CTV. Conclusions: In our series PMRI-scans had a significant impact on RT target coverage decision in pts with intermediate and high-risk prostate cancer.

The likelihood of death from prostate cancer in men with favorable or unfavorable intermediate-risk disease.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 42-42
Author(s):  
Florence K. Keane ◽  
Ming-Hui Chen ◽  
Danjie Zhang ◽  
Marian J. Loffredo ◽  
Philip W. Kantoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Risk Group ◽  
Study Cohort ◽  
Intermediate Risk ◽  
Significant Difference ◽  
Risk Prostate Cancer ◽  
Available Information

42 Background: Recently men with intermediate-risk prostate cancer (PC) were classified into favorable and unfavorable categories but whether the risk of PC-specific mortality (PCSM) amongst men with high-risk PC is higher compared to men with unfavorable intermediate-risk PC is unknown. Methods: In a prospective randomized trial conducted between 1995 and 2001, 206 men with intermediate or high-risk PC were randomized to 70 Gy with or without six months of androgen suppression therapy (AST). The subgroup of 197 patients with available information on percent positive biopsies formed the study cohort. Fine and Gray’s regression was used to assess whether men with high-risk PC had a significantly higher risk of PCSM compared to men with unfavorable intermediate-risk PC, adjusting for age, treatment, and comorbidity category. Results: After a median follow-up of 14.3 years there were 127 deaths (64.5%), of which 22 (17.3%) were from PC. There were no PC deaths in the favorable intermediate-risk group. There was no significant increase in the risk of PCSM in men with high-risk compared to unfavorable intermediate-risk PC (Adjusted Hazard Ratio: 1.59; 95% Confidence Interval: 0.66 to 3.83; P= 0.30) after adjusting for age, randomized treatment arm and comorbidity. Conclusions: Given no significant difference in the risk of PCSM in unfavorable intermediate compared with high-risk PC, these patients may merit treatment with RT and long-term AST. The lack of PC deaths in the favorable intermediate-risk group suggests that adding AST may not reduce the risk of PCSM in these patients. [Table: see text]

Gleason score upgrade among 10,282 men who underwent surgery as initial treatment in 2010: A population-based study.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 72-72
Author(s):  
Hong Zhang ◽  
Edward M. Messing ◽  
Hamza Ahmed ◽  
Yuhchyau Chen
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Gleason Score ◽  
Specific Antigen ◽  
Low Risk ◽  
Categorical Variables ◽  
Intermediate Risk ◽  
Time Of Surgery ◽  
Significant Difference ◽  
Risk Prostate Cancer

72 Background: Active surveillance is now accepted initial management for men who have localized prostate cancer with low risk of disease progression. Many criteria have been used for patient identification, including Gleason score (GS) obtained from prostate biopsy. Because of concerns of sampling error, some have recommended repeated biopsy before committing to active surveillance. However, there is limited information about the risk of missing high grade disease using the current standard biopsy approach. This study seeks to compare GS difference from biopsy and surgery to provide an estimated rate of GS upgrade. Methods: The Surveillance, Epidemiology, and End Results (SEER) program was used to identify men with American Joint Committee on Cancer stage T1-2cN0M0 prostate cancer diagnosed between January 2010 and December 2010. Patients who underwent prostatectomy were selected for further analysis. Based on prostate-specific antigen (PSA) levels and GS, cases were divided into low (PSA <=10 and GS <=6) and intermediate (10<PSA<=20 or GS=7) risk groups. The rates of GS upgrade were reported for each group. Chi-square tests were used to assess differences in categorical variables (e.g. age and race) between groups of GS upgrade and no change/downgrade. Results: A total of 10,282 men were evaluated, with 9.2% (n=942) having low-risk disease, and 90.8% (n=9340) having intermediate-risk disease. Among men with low-risk prostate cancer, 22.3% (n=210) had GS upgrade and 0.8% (n=8) had GS 8 disease. Among men with intermediate risk disease, 26.2% (n=2446) had GS upgrade and 2.3% (n=214) had GS 8 disease. There was no statistically significant difference in either age or race distribution among men who had GS upgrade versus no change or downgrade at the time of surgery. Conclusions: A substantial number of low- and intermediate-risk prostate cancer patients had GS upgrade at the time of surgery, but few had upgraded to GS 8 high risk disease. These observations suggest that repeat biopsy prior to active surveillance may not be necessary.

Prognostic value of copy-number alterations of the Cohesin complex in intermediate-risk prostate cancer recurrence.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 49-49
Author(s):  
Jonathan So ◽  
Melvin Chua ◽  
Emilie Lalonde ◽  
Osman Mahamud ◽  
Alejandro Berlin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Intermediate Risk ◽  
Cohesin Complex ◽  
Biochemical Relapse ◽  
Copy Number Alterations ◽  
Image Guided Radiotherapy ◽  
Image Guided ◽  
Risk Prostate Cancer ◽  
Pre Treatment

49 Background: The Cohesin complex plays a critical role in mitotic progression and post-replicative DNA damage repair. It serves to bring together sister chromatids both in metaphase and in homologous recombination repair following ionizing radiation. The complex has also been shown to be phosphorylated in the ATM/BRCA1 pathway. The expression of various proteins in the complex are dysregulated in many cancers: breast, prostate, etc. Interestingly, in breast cancer cell lines, Cohesin is required for MYC activation in response to estrogen. Our study sought to correlate copy number alterations in this pivotal complex with biochemical relapse in prostate cancer patients. Methods: Our cohort consists of 284 patients with D’ Amico-classified intermediate-risk prostate cancer, treated with image-guided radiotherapy (IGRT, N = 143) or radical prostatectomy (RadP, N = 141). Pre-treatment biopsies and prostatectomy samples were analyzed using the Affymetrix Oncoscan array. The Phoenix and AUA criteria was used to define biochemical relapse for RadP and IGRT patients respectively. Results: Copy number alterations of RAD21, SMC1B, and STAG1 were observed in 18% (n = 52), 6.3% (n = 18), and 12% (n = 35) of the cohort respectively. They were predominantly losses in SMC1B, but gains in RAD21 and STAG1. All three genes in the Cohesin complex were associated with increased risk of biochemical relapse: RAD21 on chromosome 8 (HR = 1.93, 95% CI 1.23, 3.02, Wald’s p = 0.004), SMC1B on chromosome 22 (HR = 3.37, 95% CI 1.91, 5.94, Wald’s p < 10-4), and STAG1 on chromosome 3 (HR = 1.74, 95% CI 1.04, 2.89, Wald’s p < 0.05). However, when controlled for percent genome alteration and pre-treatment serum PSA levels, only copy number loss of SMC1B was a significant predictor of biochemical relapse (HR = 2.95, 95% CI 1.62, 5.38, Wald’s p < 10-3). Conclusions: We identified a novel association of copy-number alterations in members of the Cohesin complex with biochemical recurrence following radical prostatectomy or image-guided radiotherapy. This points to the central role of Cohesin in cell-cycle and DNA damage pathways promoting prostate cancer progression.

Duration of androgen deprivation therapy in high risk prostate cancer: Final results of a randomized phase III trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5008-5008 ◽  
Author(s):  
Abdenour Nabid ◽  
Marie-Pierre Garant ◽  
André-Guy Martin ◽  
Jean-Paul Bahary ◽  
Celine Lemaire ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Androgen Deprivation Therapy ◽  
Cox Regression ◽  
Mixed Linear Model ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
High Risk Prostate Cancer ◽  
Significant Difference ◽  
Risk Prostate Cancer

5008 Background: Long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) is a standard treatment for patients with high-risk prostate cancer (HRPC). However, the optimal duration of ADT is not yet defined. The aim of this randomized trial (Clinical Trials.gov, #NCT00223171) was to compare outcomes of RT combined with either 36 or 18 months of ADT. Methods: Patients with HRPC were randomized to pelvic and prostate RT combined with 36 (arm 1) or 18 months (arm 2) of ADT. Overall survival (OS) and quality of life (QoL) were primary end points. OS rates were compared with Cox Regression model and QoL data were analyzed through mixed linear model. Results: 630 patients were randomized, 310 to arm 1 and 320 to arm 2. With a median follow-up of 9.4 years, 290 patients had died (147 arm 1 vs. 143 arm 2). The 10-year OS rate was 62.4% (95% confidence interval [CI] 56.4%, 67.8%) for arm 1 and 62.0% (95% CI 56.1%, 67.3%) for arm 2 (p = 0.8412) with a global hazard ratio (HR) of 1.024 (95% CI 0.813-1.289, p = 0.8411). QoL analysis showed a significant difference (p < 0.001) in 6 scales and 13 items favoring 18 months ADT with two of them presenting a clinically relevant difference in mean scores of ≥10 points. Conclusions: In HRPC, ADT combined with RT can be safely reduced from 36 to 18 months without compromising outcomes or QoL. 18 months of ADT represents a new standard of care in HRPC. Funded by AstraZeneca Pharmaceuticals Clinical trial information: NCT00223171.

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