Project description:Purpose: Patients with locally advanced prostate cancer after radical prostatectomy are candidates for secondary therapy. However, this higher risk population is heterogeneous. Many cases do not metastasize even when conservatively managed. Given the limited specificity of pathological features to predict metastasis, newer risk prediction models are needed. We report a validation study of a genomic classifier that predicts metastasis after radical prostatectomy in a high risk population. Method:A case-cohort design was used to sample 1,010 patients after radical prostatectomy at high risk for recurrence who were treated from 2000 to 2006. Patients had preoperative prostate specific antigen greater than 20 ng/ml, Gleason 8 or greater, pT3b or a Mayo Clinic nomogram score of 10 or greater. Patients with metastasis at diagnosis or any prior treatment for prostate cancer were excluded from analysis. A 20% random sampling created a subcohort that included all patients with metastasis. We generated 22-marker genomic classifier scores for 235 patients with available genomic data. ROC and decision curves, competing risk and weighted regression models were used to assess genomic classifier performance. Patients treated with RP between 2000 and 2006 were identified from the Mayo Clinic tumor registry for a case-cohort study design. This involved identification of all patients with metastasis and a representative of the full cohort .Thus, men at high risk of recurrence post-RP (open/robotic) with no prior neoadjuvant/prostate cancer treatment were selected based on any of preoperative PSA >20 ng/mL, pathological Gleason score (GS) â¥8, SVI, or GPSM (GS; preoperative PSA; SVI; margins) score â¥10.The cohort of 1,010 men included 73 cases with metastasis as evidenced by CT or bone scan. A 20% random sample (n=202) was drawn from the cohort. This included 19 of 73 metastatic cases. To increase sampling of metastasis, the remaining 54 metastatic cases were added, resulting in a final study set of 256 patients. 21 samples did not pass QC and were eliminated from this study. Patients not experiencing metastasis regardless of BCR (defined as follow-up PSA â¥0.4 ng/mL >30 days post-RP) were censored at last follow-up. The study was approved by Mayo Clinic Institutional Review Board.

Project description:After therapy for prostate cancer many men develop a rising PSA. Such men may develop a local or metastatic recurrence that warrants further therapy. However many men will have no evidence of disease progression other than the rising PSA and will have a good outcome. A case-control design, incorporating test and validation cohorts, was used to test the association of gene expression results with outcome after PSA recurrence. Since clinical training and validation analysis requires tissue from patients with sufficient follow-up time, for this study we sampled individuals from the Mayo Radical Retropubic Prostatectomy (RRP) Registry. The registry consists of a population of men who received prostatectomy as their first treatment for prostate cancer at the Mayo Clinic (For a current description and use of the registry; see PMID: 17418069). As systemic progression is relatively infrequent, we designed a case-control study nested within a cohort of men with a rising PSA. Between 1987-2001, inclusive, 9,989 previously-untreated men had RRP at Mayo. On follow-up, 2,131 developed a rising PSA (>30 days after RRP) in the absence of concurrent clinical recurrence. PSA rise was defined as a follow-up PSA >= 0.20 ng/ml, with the next PSA at least 0.05 ng/ml higher or the initiation of treatment for PSA recurrence (for patients whose follow-up PSA was high enough to warrant treatment). This group of 2,131 men comprises the underlying cohort from which SYS cases and PSA controls were selected. Within 5 years of PSA rise, 213 men developed systemic progression (SYS cases), defined as a positive bone scan or CT scan. Of these, 100 men succumbed to a prostate cancer-specific death, 37 died from other causes and 76 remain at risk. PSA recurrence controls (213) were selected from those men without systemic progression within 5 years after the PSA rise and were matched (1:1) on birth year, calendar year of PSA rise and initial diagnostic pathologic Gleason score (<=6, 7+). Twenty of these men developed systemic progression greater than 5 years after initial PSA rise and 9 succumbed to a prostate cancer-specific death. A set of 213 No Evidence of Disease (NED) Progression controls were also selected from the Mayo RRP Registry of 9,989 men and used for some comparisons. These controls had RRP from 1987-1998 with no evidence of PSA rise within 7 years of RRP. The median (25th, 75th percentile) follow-up from RRP was 11.3 (9.3, 13.8) years. The NED controls were matched to the systemic progression cases on birth-year, calendar year of RRP and initial diagnostic Gleason Score. Computerized optimal matching was performed to minimize the total distance between cases and controls in terms of the sum of the absolute difference in the matching factors (PMID: 8728456). All paraffin-embedded blocks from eligible men were identified and each block was surveyed for the tissue present (primary and secondary Gleason cancer regions, normal and metastatic lymph nodes, etc.). Of the 639 eligible patients, paraffin blocks were available on 623 (97.5%). Similarly, RNA was successfully isolated and the DASL assays successfully performed on a very high proportion of patients/specimens: Usable RNA was prepared from all 623 blocks, and the Cancer Panel and custom prostate cancer panel DASL arrays were both successful on 596 RNA specimens (95.7% of RNAs; 93.3% of design patients). Keywords: outcome prediction 596 total cases (n=200, 201, 195 for systemic disease progression, PSA recurrence and no evidence of disease groups).

Project description:After therapy for prostate cancer many men develop a rising PSA. Such men may develop a local or metastatic recurrence that warrants further therapy. However many men will have no evidence of disease progression other than the rising PSA and will have a good outcome. A case-control design, incorporating test and validation cohorts, was used to test the association of gene expression results with outcome after PSA recurrence. Since clinical training and validation analysis requires tissue from patients with sufficient follow-up time, for this study we sampled individuals from the Mayo Radical Retropubic Prostatectomy (RRP) Registry. The registry consists of a population of men who received prostatectomy as their first treatment for prostate cancer at the Mayo Clinic (For a current description and use of the registry; see PMID: 17418069). As systemic progression is relatively infrequent, we designed a case-control study nested within a cohort of men with a rising PSA. Between 1987-2001, inclusive, 9,989 previously-untreated men had RRP at Mayo. On follow-up, 2,131 developed a rising PSA (>30 days after RRP) in the absence of concurrent clinical recurrence. PSA rise was defined as a follow-up PSA >= 0.20 ng/ml, with the next PSA at least 0.05 ng/ml higher or the initiation of treatment for PSA recurrence (for patients whose follow-up PSA was high enough to warrant treatment). This group of 2,131 men comprises the underlying cohort from which SYS cases and PSA controls were selected. Within 5 years of PSA rise, 213 men developed systemic progression (SYS cases), defined as a positive bone scan or CT scan. Of these, 100 men succumbed to a prostate cancer-specific death, 37 died from other causes and 76 remain at risk. PSA recurrence controls (213) were selected from those men without systemic progression within 5 years after the PSA rise and were matched (1:1) on birth year, calendar year of PSA rise and initial diagnostic pathologic Gleason score (<=6, 7+). Twenty of these men developed systemic progression greater than 5 years after initial PSA rise and 9 succumbed to a prostate cancer-specific death. A set of 213 No Evidence of Disease (NED) Progression controls were also selected from the Mayo RRP Registry of 9,989 men and used for some comparisons. These controls had RRP from 1987-1998 with no evidence of PSA rise within 7 years of RRP. The median (25th, 75th percentile) follow-up from RRP was 11.3 (9.3, 13.8) years. The NED controls were matched to the systemic progression cases on birth-year, calendar year of RRP and initial diagnostic Gleason Score. Computerized optimal matching was performed to minimize the total distance between cases and controls in terms of the sum of the absolute difference in the matching factors (PMID: 8728456). All paraffin-embedded blocks from eligible men were identified and each block was surveyed for the tissue present (primary and secondary Gleason cancer regions, normal and metastatic lymph nodes, etc.). Of the 639 eligible patients, paraffin blocks were available on 623 (97.5%). Similarly, RNA was successfully isolated and the DASL assays successfully performed on a very high proportion of patients/specimens: Usable RNA was prepared from all 623 blocks, and the Cancer Panel and custom prostate cancer panel DASL arrays were both successful on 596 RNA specimens (95.7% of RNAs; 93.3% of design patients). Keywords: outcome prediction

Project description:Current prostate cancer prognostic models are based on pre-treatment prostate-specific antigen (PSA) levels, biopsy Gleason score, and clinical staging but in practice are inadequate to accurately predict clinical disease progression. Hence, we sought to develop a molecular panel for prostate cancer progression by reasoning that molecular profiles might further improve current clinical models. We analyzed a Swedish Watchful Waiting cohort (1977â1999) with up to 30 years of clinical follow up using a novel method for gene expression profiling. This cDNA-mediated annealing, selection, ligation, and extension (DASL) method enabled the use of formalin-fixed paraffin-embedded transurethral resection of prostate (TURP) samples taken at the time of the initial diagnosis. We determined the expression profiles of 6100 genes for 281 men divided in two extreme groups: men who died of prostate cancer or developed metastases and men who survived more than 10 years without metastases (lethals and indolents, respectively). Several models using clinical and molecular features were evaluated for their ability to distinguish lethal from indolent cases. Surprisingly, none of the predictive models using molecular profiles significantly improved over models using clinical variables only. We reasoned that tumor sampling might preclude the identification of the dominant metastatic nodule. Additional computational analysis confirmed that molecular heterogeneity within both the lethal and indolent classes is widespread in prostate cancer as compared to other types of tumors. Thus the determination of the molecularly dominant tumor nodule may be limited by sampling at time of initial diagnosis, may not be present at time of initial diagnosis, or may occur as the disease progresses preventing the development of molecular biomarkers for prostate cancer progression. 281 cases from the population-based Swedish-Watchful Waiting cohort. The cohort consists of men with localized prostate cancer (clinical stage T1-T2, Mx, N0); Training set: first 186 samples; Validation cohort: remaining 95 cases from the same population.

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	Study_Report.phs000838.ProstateCancer_WestAfricanMen.v1.p1.MULTI.pdf	Pdf
	manifest_phs000838.ProstateCancer_WestAfricanMen.v1.p1.c1.DS-UC-MDS.pdf	Pdf
	datadict_v2.xsl	Other

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Ghana Prostate Study

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