Implants of noninvasive papillary urothelial carcinoma in peritoneum and ileocolonic neobladder: support for "seed and soil" hypothesis of bladder recurrence.

OBJECTIVES: To explore the underlying mechanism of tumor regrowth in cases of noninvasive urothelial carcinoma that recur in unusual anatomic locations. METHODS: The pathology files of our institution and the consult service of one of us were searched for cases of noninvasive nonmetastatic urothelial carcinoma with involvement of unusual anatomic sites. Cases in which the mode of spread included direct spread to the adjacent tissue and lymphovascular metastases were excluded. Medical history, including presenting symptoms, and follow-up data were obtained. RESULTS: Two cases of noninvasive urothelial carcinoma were identified. One had presented as an implant in the peritoneal investment of the bladder dome and the other as multiple implants growing on the benign surface of the colonic mucosa of an orthotopic neobladder distant from the anastomosis site. Both cases had initially presented as noninvasive papillary urothelial carcinoma of the renal pelvis. Although the urinary bladder was free of neoplastic changes at nephroureterectomy, both patients also developed several papillary tumors within the bladder shortly after the removal of the kidney. CONCLUSIONS: After clinicopathologic correlation, the mode of tumor spread in these cases was best explained by the "seeding/implantation" theory. The urothelial tumor cells in each of these cases demonstrated the ability to implant themselves not only in the urothelium of the bladder but also in the colonic mucosa of a constructed neobladder and on the peritoneal surface.

Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer.

PURPOSE: As kinase inhibitors transition from the laboratory to patients, it is imperative to develop biomarkers that can be used in the clinic. The primary objectives are to identify patients most likely to benefit from molecularly targeted therapies and to document modulation of the drug target. Constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway and its downstream effectors, as a result of PTEN loss or by other mechanisms, occurs in a high proportion of prostate cancers, making it an ideal template for the design of clinical trials involving PI3K pathway inhibitors. Prostate cancers also present unique organ-specific challenges, in that tumors are heterogeneous and diagnostic tissue is extremely limited. EXPERIMENTAL DESIGN: Working within these limitations, we have developed a set of immunohistochemical assays that define activation of the PI3K pathway in clinical samples. RESULTS AND CONCLUSIONS: Using both univariate and multivariate analyses, we show that loss of PTEN is highly correlated with the activation of AKT, and this, in turn, is associated with the phosphorylation of S6, one of its main effectors. These three antibodies are potentially able to define a molecular signature of PTEN loss and/or AKT pathway activation in prostate cancer.

Dietary boron intake and prostate cancer risk.

Boron affects human steroid hormone levels. Circulating testosterone and estradiol levels have been proposed to modify prostate cancer risk. However, the association between dietary boron intake and the risk of prostate cancer has not been evaluated by any epidemiological study. We explored the association between dietary boron intake and the risk of prostate cancer in the USA. Our analysis was based on data from the third National Health and Nutrition Examination Survey (NHANES III). Cross-sectional case-control study design was employed by comparing boron intake of 95 prostate cancer cases with that of 8,720 male controls. After controlling for age, race, education, smoking, body mass index, dietary caloric intake, and alcohol consumption, increased dietary boron intake was associated with a decreased risk of prostate cancer with a dose-response pattern. The adjusted odds ratio was 0.46 (95% confidence interval: 0.21-0.98) for the highest quartile of boron intake comparing to the lowest quartile (P for trend = 0.0525). The observed association should be interpreted with caution because of the small case sample size and the nature of the cross-sectional study design, but deserve further investigation.

International validation of a preoperative nomogram for prostate cancer recurrence after radical prostatectomy.

PURPOSE: We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS: Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS: The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION: The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

Validation study of the accuracy of a postoperative nomogram for recurrence after radical prostatectomy for localized prostate cancer.

PURPOSE: A postoperative nomogram for prostate cancer was developed at Baylor College of Medicine. This nomogram uses readily available clinical and pathologic variables to predict 7-year freedom from recurrence after radical prostatectomy. We evaluated the predictive accuracy of the nomogram when applied to patients of four international institutions. PATIENTS AND METHODS: Clinical and pathologic data of 2,908 patients were supplied for validation, and 2,465 complete records were used. Nomogram-predicted probabilities of 7-year freedom from recurrence were compared with actual follow-up in two ways. First, the area under the receiver operating characteristic curve (AUC) was calculated for all patients and stratified by the time period of surgery. Second, calibration of the nomogram was achieved by comparing the predicted freedom from recurrence with that of an ideal nomogram. For patients in whom the pathologic report does not distinguish between focal and established extracapsular extension (an input variable of the nomogram), two separate calculations were performed assuming one or the other. RESULTS: The overall AUC was 0.80 when applied to the validation data set, with individual institution AUCs ranging from 0.77 to 0.82. The predictive accuracy of the nomogram was apparently higher in patients who were operated on between 1997 and 2000 (AUC, 0.83) compared with those treated between 1987 and 1996 (AUC, 0.78). Nomogram predictions of 7-year freedom from recurrence were within 10% of an ideal nomogram. CONCLUSION: The postoperative Baylor nomogram was accurate when applied at international treatment institutions. Our results suggest that accurate predictions may be expected when using this nomogram across different patient populations.