Accuracy of the Kattan nomogram across prostate cancer risk-groups
ABSTRACT • To investigate the predictive ability of nomograms at the extremes of preoperative clinical parameters by examining the predictive ability across all prostate cancer risk groups.
• The Columbia University Urologic Oncology Database was reviewed: 3663 patients underwent radical prostatectomy from 1988 to 2008. Patients who had received neoadjuvant or adjuvant therapy, or had insufficient clinical parameters for estimation of 5-year progression-free probability using the preoperative Kattan nomogram were excluded. • A total of 1877 patients were included and stratified by D'Amico risk criteria. Mean estimated nomogram progression rates were compared with actuarial Kaplan-Meier survival statistics. • A regression model to predict progression-free survival was fitted with estimated nomogram score and concordance indices were calculated for the entire model and subsequently for each risk group.
• Of 1877 patients, 857 (45.6%) were low risk, 704 (37.5%) were intermediate risk, and 316 (16.8%) were high risk by D'Amico criteria. • Mean estimated nomogram survival and actuarial Kaplan-Meier survival at 5 years were 90.5% and 92.2% (95% CI 89.2-94.3) for low-risk, 76.7% and 77.8% (73.3-81.7) for intermediate-risk, and 65.8% and 60.4% (52.0-67.7) for high-risk groups, respectively. Using nomogram score in the regression model, the c-index for the full model was 0.61. • For low-, intermediate- and high-risk patients independently the c-index was 0.60, 0.59 and 0.57, respectively. When low-, intermediate- and high-risk patients were independently removed from the model the c-index was 0.64, 0.65 and 0.55, respectively. • The c-index for the full model using the categorical nomogram risk scores was 0.67. Similar to the D'Amico model, the c-index improved to 0.69 when intermediate-risk patients were removed from the model.
• The study confirms the ability of preoperative nomograms to accurately predict actuarial survival across all risk groups. • The predictive ability of the nomogram varies by risk group, yet even at the extremes of high-risk and low-risk prostate cancer the nomogram accurately predicts outcome.
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ABSTRACT: Today, the majority of men with newly diagnosed prostate cancer will present with low-risk features of the disease. Because prostate cancer often takes an insidious course, it is debated whether the majority of these men require radical treatment and the accompanying derangement of quality of life domains imposed by surgery, radiation, and hormonal therapy. Investigators have identified various selection criteria for "insignificant disease," or that which can be monitored for disease progression while safely delaying radical treatment. In addition to the ideal definition of low risk, a lack of randomized trials comparing the various options for treatment in this group of men poses a great challenge for urologists. Early outcomes from active surveillance cohorts support its use in carefully selected men with low-risk disease features, but frequent monitoring is required. Patient selection and disease monitoring methods will require refinement that will likely be accomplished through the increased use of biomarkers and specialized imaging techniques.Korean journal of urology 07/2013; 54(7):417-25. DOI:10.4111/kju.2013.54.7.417
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ABSTRACT: What's known on the subject? and What does the study add? L-dopa decarboxylase (DDC) has been documented as a novel co-activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH. In the present study, there was a significant association between the DDC gene expression levels and the pathological stage and Gleason score of patients with prostate cancer (PCa). Moreover, DDC expression was shown to be an unfavourable prognostic marker of biochemical recurrence and disease-free survival in patients with PCa treated by radical prostatectomy. To determine whether L-dopa decarboxylase gene (DDC) expression levels in patients with prostate cancer (PCa) correlate to biochemical recurrence and disease prognosis after radical prostatectomy (RP). The present study consisted of 56 samples with confirmed malignancy from patients with PCa who had undergone RP at a single tertiary academic centre. Total RNA was isolated from tissue specimens and a SYBR Green fluorescence-based quantitative real-time polymerase chain reaction methodology was developed for the determination of DDC mRNA expression levels of the tested tissues. Follow-up time ranged between 1.0 and 62.0 months (mean ± SE, 28.6 ± 2.1 month; median, 31.5 months). Time to biochemical recurrence was defined as the interval between the surgery and the measurement of two consecutive values of prostate-specific antigen (PSA) ≥0.2 ng/mL. DDC expression levels were found to be positively correlated with the tumour-node-metastasis stage (P = 0.021) and Gleason score (P = 0.036) of the patients with PCa. Patients with PCa with raised DDC expression levels run a significantly higher risk of biochemical recurrence after RP, as indicated by Cox proportional regression analysis (P = 0.021). Multivariate Cox proportional regression models revealed the preoperative PSA-, age- and digital rectal examination-independent prognostic value of DDC expression for the prediction of disease-free survival (DFS) among patients with PCa (P = 0.036). Kaplan-Meier survival analysis confirms the significantly shorter DFS after RP of PCa with higher DDC expression levels (P = 0.015). This is the first study indicating the potential of DDC expression as a novel prognostic biomarker in patients with PCa who have undergone RP. For further evaluation and clinical application of the findings of the present study, a direct analysis of mRNA and/or its protein expression level in preoperative biopsy, blood serum and urine should be conducted.BJU International 05/2012; 110(6 Pt B):E267-73. DOI:10.1111/j.1464-410X.2012.11152.x · 3.13 Impact Factor
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ABSTRACT: Androgen deprivation therapy (ADT) and novel agents targeting the androgen synthesis axis (e.g., abiraterone acetate) are adjuvant therapies that are currently, or may in the future be, combined with radiotherapy to reduce the chance of disease relapse. Little is known about allelic loss or gain pertaining to genes associated with the androgen synthesis axis and whether this is prognostic in patients who receive localized radiotherapy. In this hypothesis generating study, we conducted an array comparative genomic hybridization (aCGH) analysis of 33 androgen synthesis genes to identify potential prognostic factors for radiotherapy outcome. aCGH analysis of tumor DNA prospectively derived from frozen needle biopsies of 126 men with intermediate-risk disease who underwent image-guided radiotherapy (IGRT) to a mean dose of 76.4 Gy was conducted. Statistical analyses were conducted for allelic loss or gain in genes as potential prognostic factors relative to prostate specific antigen, Gleason-score, and T-category. We observed that allelic losses of loci containing the genes StAR and HSD17B2 were associated with increased genetic instability (as determined by percentage genome alteration). On multivariate analyses these loci were prognostic for biochemical disease-free relapse (StAR: HR = 2.84, 95% CI: 1.44-5.61, P = 0.00269; HSD17B2: HR = 1.97, 95% CI: 1.06-3.64, P = 0.031). The results were validated in a surgical cohort of 131 intermediate-risk patients. Allelic losses of the loci containing StAR and HSD17B2 have significant prognostic value for intermediate-risk prostate cancer. With this hypothesis generating information future studies should test StAR and HSD17B2 losses as biomarkers of androgen response in combined modality protocols.The Prostate 09/2012; 72(12):1295-305. DOI:10.1002/pros.22478 · 3.57 Impact Factor