Limited options for the treatment of prostate cancer have spurred the search for new therapies. One innovative approach is the use of 1alpha,25-dihydroxyvitamin D3 (calcitriol) analogues to inhibit ...cancer growth. We demonstrate here that the calcitriol analogue, EB1089, extensively inhibits the growth of LNCaP prostate cancer cells in culture and causes the cells to both accumulate in G0-G1 and undergo apoptosis. Importantly, we found that EB1089 inhibits the growth of LNCaP tumor xenografts in nude mice. Because of these antiproliferative properties in vivo, EB1089 is a potential new therapeutic agent for the treatment of prostate cancer.
We determined the frequency of tumor multifocality in patients with renal cortical tumors, characterized clinical and pathological features associated with multifocality and evaluated its effect on ...patient survival.
Between July 1989 and July 2002, 1,071 radical nephrectomies were performed at our institution. Specimens were examined grossly and microscopically for multifocal tumors. Preoperative imaging was reviewed to determine whether multifocality was suspected prior to operation. Multivariate analysis was performed to identify clinical and pathological factors associated with multifocality.
Of 1,071 radical nephrectomy specimens 57 (5.3%) had pathological evidence of tumor multifocality. Bilateral synchronous renal cortical tumors were present in 6 of the 57 multifocal cases (11%). A total of 19 cases (33%) had evidence of multifocality on preoperative imaging and, therefore, occult multifocality undetected on preoperative imaging was present in 3.5% of radical nephrectomies (38 of 1,071). Primary tumors in the multifocal group were most commonly conventional clear cell carcinoma, followed by papillary carcinoma. Of multifocal cases 74% had the same histological subtype in all tumors. Multivariate analysis demonstrated that bilaterality, papillary subtype, advanced tumor stage and lymph node metastasis were associated with multifocality. At a median follow up of 40.5 months overall survival, disease-free survival, and disease-free probability were not significantly different between the multifocal and unifocal groups.
We report a 5.3% frequency of multifocal renal cortical tumors and a 3.5% frequency of clinically unsuspected multifocal tumors. Multifocality had no apparent effect on recurrence or survival in patients who underwent radical nephrectomy.
Objectives. Early detection of prostate cancer traditionally involves both digital rectal examination (DRE) and serum prostate-specific antigen (PSA) determination in an informed patient population. ...Abnormalities in either of these studies typically lead to additional evaluations, including prostate biopsy. In this study, we analyzed the operational characteristics of serum PSA between 0 and 4 ng/mL as an initial test for prostate cancer.
Methods. From January 1990 through May 1997, transrectal biopsies were obtained from 700 men with a serum PSA level less than 4.0 ng/mL but DRE suspicious for cancer. Patient age, race, and serum PSA level were reviewed for this study.
Results. Of the 700 men studied, 445 were white (64%) and 255 were African American (36%). In multivariate analysis of prebiopsy risk factors (age, race, serum PSA), serum PSA was the only independent predictor of a positive prostate biopsy. A nomogram was created that determines the worst-case probability of a positive prostate biopsy in men with PSA between 0 and 4 ng/mL and a DRE suspicious for cancer. The predictions from the nomogram appeared accurate and discriminating, with a bias-corrected area under the receiver operating characteristic curve (ie, comparison of the predicted probability with the actual outcome) of 0.75.
Conclusions. Although early detection of prostate cancer has traditionally used both PSA measurement and DRE, PSA testing alone could be more easily implemented and may encourage some men to seek consultation who might not otherwise have done so. By providing a nomogram which provides a worse-case scenario (assuming a positive DRE) of the probability of a positive biopsy, the patient and clinician can make an informed decision as to whether additional evaluation is warranted.
Although prostate cancer is found in about 30% of patients at the initial biopsy session, there is a need to identify those with a negative result but who are at high risk. Although individual risk ...factors have been found to be associated with cancer, patient counseling requires the integration of multiple risk factors to obtain a prediction for the individual.
We studied 343 patients with at least 1 initial negative biopsy who were tested from August 1999 to September 2001. At each biopsy session we recorded patient age, family history of prostate cancer, serum prostate specific antigen (PSA), PSA slope, digital rectal examination findings, months from the initial biopsy session, cumulative number of negative cores previously obtained, and history of high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. Through Cox regression analysis we determined the association of each variable with time to a positive biopsy. A nomogram was constructed using all variables and discrimination was calculated as the concordance index.
There were 661 biopsy sessions. A mean of 2.9 biopsy sessions were performed per patient and a mean of 9.15 cores were obtained per biopsy session for a mean of 25.2 per patient. Overall 20% of patients had cancer at the second biopsy session. The cumulative number of negative cores obtained, PSA slope, history of high grade prostatic intraepithelial neoplasia and history of atypical small acinar proliferation were associated with repeat biopsy findings (all p <0.05). A nomogram was constructed that had a concordance index of 0.70, which was greater than that of any single risk factor.
We created a nomogram that predicts a positive biopsy after a previous negative biopsy session. It provides a wide range of probabilities for cancer and may improve clinical judgment before the decision to repeat biopsy.
Abstract Objective. Nomograms have been developed for numerous malignancies to predict a specific individual's probability of long-term survival based on known prognostic factors. To date, only one ...prediction model has been reported for patients with epithelial ovarian carcinoma (EOC). The objective of this study was to develop a more accurate survival nomogram for patients with bulky stage IIIC EOC. Patients and methods. Nomogram predictor variables included age, tumor grade, histologic type, preoperative platelet count, ascites, and residual disease after primary cytoreduction. Disease-specific survival was estimated by the Kaplan–Meier method. Cox proportional hazards regression was used for multivariate analysis, which was the basis for the nomogram. The concordance index was used as an accuracy measure with bootstrapping to correct for optimistic bias. Results. A total of 424 evaluable patients with bulky stage IIIC EOC underwent primary surgery at our institution during the study period of 1/89 to 12/03. All patients received postoperative platinum-based systemic chemotherapy. EOC-specific survival at 5 years was 51%. Using the six predictor variables, a nomogram was constructed and internally validated using bootstrapping. It was shown to have excellent calibration with a bootstrap corrected concordance index of 0.67, which was more accurate in predicting survival at this stage than the previously published model (concordance index = 0.53). Conclusion. Utilizing six readily accessible predictor variables, our nomogram more accurately predicted 5-year disease-specific survival for bulky stage IIIC EOC than the previously published model. This tool may be useful for patient counseling, determination of clinical trial eligibility, and postoperative management.
Introduction. The objective of this study was to create a tool that accurately predicts the risk of morbidity and mortality in patients with type 2 diabetes according to an oral hypoglycemic agent. ...Materials and Methods. The model was based on a cohort of 33,067 patients with type 2 diabetes who were prescribed a single oral hypoglycemic agent at the Cleveland Clinic between 1998 and 2006. Competing risk regression models were created for coronary heart disease (CHD), heart failure, and stroke, while a Cox regression model was created for mortality. Propensity scores were used to account for possible treatment bias. A prediction tool was created and internally validated using tenfold cross-validation. The results were compared to a Framingham model and a model based on the United Kingdom Prospective Diabetes Study (UKPDS) for CHD and stroke, respectively. Results and Discussion. Median follow-up for the mortality outcome was 769 days. The numbers of patients experiencing events were as follows: CHD (3062), heart failure (1408), stroke (1451), and mortality (3661). The prediction tools demonstrated the following concordance indices (c-statistics) for the specific outcomes: CHD (0.730), heart failure (0.753), stroke (0.688), and mortality (0.719). The prediction tool was superior to the Framingham model at predicting CHD and was at least as accurate as the UKPDS model at predicting stroke. Conclusions. We created an accurate tool for predicting the risk of stroke, coronary heart disease, heart failure, and death in patients with type 2 diabetes. The calculator is available online at http://rcalc.ccf.org under the heading "Type 2 Diabetes" and entitled, "Predicting 5-Year Morbidity and Mortality." This may be a valuable tool to aid the clinician's choice of an oral hypoglycemic, to better inform patients, and to motivate dialogue between physician and patient.
Objective
Prostate cancer (PCa) incidence has been rising rapidly in Korea with aggressive clinicopathologic features compared to those observed in Western countries. Our aim was to develop a ...predictive nomogram for BCR-free survival based on the characteristics of PCa in Korean men and compared its predictive accuracy to an established Western nomogram.
Methods
A nationwide multicenter study was designed involving 723 Korean men with clinically localised PCa that had undergone radical prostatectomy. The Cox proportional hazards model was applied to 549 cases from four heavy volume institutions to define prognostic factors and develops the Korean nomogram, which was subjected to internal validation, external validation using a separate cohort of 295 cases, and head-to-head comparison with the updated Kattan nomogram.
Results
During the mean follow-up period of 44.8 months, BCR occurred in 251 patients (35.4 %) with aggressive clinicopathologic features. Similar to Western cases, preoperative prostate-specific antigen (PSA), pathologic tumour stage (pT), and Gleason score (GS) were independent prognostic factors and used to develop the Korean nomogram in conjunction with age and surgical margin status. The Korean nomogram performed well for predicting BCR-free 5- and 10-year survival on internal validation. On external validation, the Korean nomogram showed better calibration than the updated Kattan nomogram.
Conclusions
Preoperative PSA, pT, and GS were independent prognostic factor for BCR in clinically localised PCa in Korean men. The superior performance of the Korean nomogram for Korean PCa patients suggests that geographic variation in clinicopathologic factors should be considered in a predictive nomogram.
Objective. A difficulty with applying decision analysis at the bedside is that it generally requires computer software for the calculations, which may render the method impractical. The purpose of ...this study was to illustrate the feasibility of developing a regression model that approximates the results from a published decision-analytic model for prostate cancer and permits bedside generation of personalized decision-analytic recommendations with a paper nomogram. Methods. The authors used the example of radical prostatectomy v. watchful waiting for patients with early-stage prostate cancer. First, they took a published decision analysis and generated recommendations using simulated data where patient baseline factors and preference scores for health states were systematically varied. Multivariable logistic regression was used to identify the parameters with strong associations with the recommendation. A reduced model was fit that excluded other preference scores except for watchful waiting. They compared the recommended management predictive accuracies from the full v. reduced model at the individual patient level for 63 men from another published study. Discrimination was assessed using receiver operating characteristic (ROC) curve analysis. A nomogram was constructed from the covariates in the reduced model. Results. The reduced logistic regression model predicted the recommendations accurately for the 63 patients, with an area under the ROC curve of 0.92. Discrimination was excellent as demonstrated by histograms. Conclusions. The authors demonstrated that logistic regression modeling allows accurate reproduction of decision-analytic recommendations with simplified calculations, which can be accomplished using a graphic nomogram. This approach should facilitate clinical decision analysis at the bedside.
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