Faculty Bibliography

PURPOSE: The Partin tables are a nomogram that is widely used to discriminate prostate cancer pathological stages, given common preoperative clinical characteristics. The nomogram is based on patients undergoing radical prostatectomy at The Johns Hopkins Medical Institutions. We validated the Partin tables in a large, population based sample. MATERIALS AND METHODS: The National Cancer Institute Surveillance, Epidemiology and End Results database was used to identify patients treated from 2004 to 2005 who underwent radical prostatectomy. The 2007 Partin tables were used to estimate the prevalence of positive lymph nodes, seminal vesicle invasion, extraprostatic extension and organ confined disease in men with prostate cancer in the database using clinical stage, preoperative prostate specific antigen and Gleason score. The discriminative ability of the tables was explored by constructing ROC curves. RESULTS: We identified 11,185 men who underwent radical prostatectomy for prostate cancer in 2004 to 2005. The Partin tables discriminated well between patient groups at risk for positive lymph nodes and seminal vesicle invasion (AUC 0.77 and 0.74, respectively). The discrimination of extraprostatic extension and organ confined disease was more limited (AUC 0.62 and 0.68, respectively). The AUC for positive lymph nodes was 0.78 in white men, 0.73 in black men and 0.83 in Asian/Pacific Islander men (p = 0.17). The AUC for positive lymph nodes in men 61 years old or younger was 0.80 vs 0.74 in men older than 61 years (p = 0.03). CONCLUSIONS: The Partin tables showed excellent discrimination for seminal vesicle invasion and positive lymph nodes. Discrimination of extraprostatic extension and organ confined disease was more limited. The Partin tables performed best in young men

PURPOSE: We assessed the association of quantitative clinical and pathologic information, including serum and tissue pro-prostate-specific antigen (proPSA) measurements, with outcomes among men with prostate cancer in an expectant management (active surveillance) program. EXPERIMENTAL DESIGN: We identified 71 men enrolled in expectant management with frozen serum and tissue available from diagnosis: 39 subsequently developed unfavorable biopsies (Gleason score > or =7, > or =3 cores positive for cancer, >50% of any core involved with cancer), whereas 32 maintained favorable biopsies (median follow-up, 3.93 years). Serum total PSA, free PSA (fPSA), and [-2]proPSA were measured by the Beckman Coulter immunoassay. [-5/-7]proPSA was evaluated in cancer and benign-adjacent areas (BAA) by quantitative immunohistochemistry. Cox proportional hazards and Kaplan-Meier analyses were used to identify significant associations with unfavorable biopsy conversion. RESULTS: The ratio [-2]proPSA/% fPSA in serum was significantly higher at diagnosis (0.87 +/- 0.44 versus 0.65 +/- 0.36 pg/mL; P = 0.02) in men developing unfavorable biopsies. [-5/-7]proPSA tissue staining was more intense (4104.09 +/- 3033.50 versus 2418.06 +/- 1606.04; P = 0.03) and comprised a greater fractional area (11.58 +/- 7.08% versus 6.88 +/- 5.20%; P = 0.01) in BAA of these men. Serum [-2]proPSA/% fPSA [hazard ratio, 2.53 (1.18-5.41); P = 0.02], BAA [-5/-7]proPSA % area [hazard ratio, 1.06 (1.01-1.12); P = 0.02] and BAA [-5/-7]proPSA stain intensity [hazard ratio, 1.000213 (1.000071-1.000354); P = 0.003] were significantly associated with unfavorable biopsy in Kaplan-Meier and Cox analyses. Serum [-2]proPSA/% fPSA significantly correlated with BAA [-5/-7]proPSA % area (rho = 0.40; P = 0.002) and BAA [-5/-7]proPSA stain intensity (rho = 0.33; P = 0.016). CONCLUSIONS: In a prospective cohort of men enrolled into expectant management for prostate cancer, serum and tissue levels of proPSA at diagnosis are associated with need for subsequent treatment. The increase in serum proPSA/% fPSA might be driven by increased proPSA production from 'premalignant' cells in the prostate BAA

The development of biomarkers for prostate cancer screening, detection, and prognostication has revolutionized the management of this disease. Prostate-specific antigen (PSA) is a useful, though not specific, biomarker for detecting prostate cancer. We review the literature on prostate cancer biomarkers, including serum markers (PAP, tPSA, fPSA, proPSA, PSAD, PSAV, PSADT, EPCA, and EPCA-2), tissue markers (AMACR, methylated GSTP1, and the TMPRSS2-ETS gene rearrangement), and a urine marker (DD3PCA3/UPM-3). Future research should focus on validation of already existing biomarkers and the discovery of new markers to identify men with aggressive prostate cancer

OBJECTIVES: To test whether patients with clinical Stage T2a prostate cancer with biopsy-proven disease only contralateral to the palpable abnormality experience outcomes similar to those of patients with clinical Stage T1c. METHODS: We identified 1567 patients who had undergone radical prostatectomy at our institution from 1995 to 2007 with a prostate-specific antigen level of less than 10 ng/mL and complete information regarding the laterality of positive biopsy cores. Of these patients, 1157 had clinical Stage T1c and 410 Stage cT2a. The patients with clinical Stage T2a were divided into two groups according to the laterality of the positive biopsy cores: ipsilateral only (n = 241) and contralateral only (n = 53). Kaplan-Meier analyses were used to compare the biochemical recurrence-free survival (BRFS) probabilities. RESULTS: The patients with clinical Stage T2a had significantly poorer 5-year BRFS than did the patients with clinical Stage T1c (83.5% versus 94.4%, P <0.001). The difference in BRFS between the contralateral and ipsilateral clinical Stage T2a groups was statistically insignificant. A significant difference was found in BRFS between patients with cT1c and cT2a ipsilateral disease. A statistically insignificant difference in BRFS was found between patients with cT1c and cT2a contralateral disease. CONCLUSIONS: The laterality of the needle biopsy in relation to the palpable abnormality in patients with clinical Stage T2a could affect BRFS. Our data have demonstrate an insignificant difference between patients with cT2a contralateral disease and those with contralateral cT1c disease

OBJECTIVES: The new American Society for Therapeutic Radiology and Oncology/Radiation Therapy Oncology Group consensus definition of biochemical failure after radiotherapy for prostate cancer is defined as a prostate-specific antigen level at or greater than the absolute nadir PSA level plus 2 ng/mL. Because this definition inevitably will be used to compare cancer control rates after radiotherapy to those after surgery, this study examined the effect of this comparison. METHODS: We reviewed the data from 2570 men who had undergone radical prostatectomy from 1985 to 2004. Biochemical failure was defined as any measurable PSA level of 0.2 ng/mL or greater. We evaluated how the nadir+2 definition affected the failure rate when applied to this series. RESULTS: The actuarial 5, 10, and 15-year biochemical recurrence-free survival probability with failure defined as a PSA level of 0.2 ng/mL or more and a PSA level of 2 ng/mL or more was 88.6%, 81.2%, and 78.1% and 94.6%, 89.4%, and 84.3%, respectively (P <0.0001). The median time to biochemical progression was 2.8 years for the greater than 0.2 ng/mL definition and 7.9 years for the 2 ng/mL or more definition. The nadir+2 definition systematically overestimated the biochemical recurrence-free survival, even after stratifying patients into standard prognostic risk groups, especially in men who developed local recurrence. CONCLUSIONS: When applied to a mature series of surgically treated patients with localized prostate cancer, the American Society for Therapeutic Radiology and Oncology 'nadir+2' definition resulted in a systematic delay in the determination of biochemical failure. Because patients in this series who experienced a detectable PSA level took more than 5 years to progress to a PSA level of 2 ng/mL or greater, the 5-year biochemical control rates with the definition of 0.2 ng/mL or more should be compared with the 10-year biochemical control rates using the nadir+2 definition

BACKGROUND: p300 impacts the transcription of several genes involved in key pathways critical to PCa progression. Therefore, we evaluated the prognostic value of p300 expression and its correlation with nuclear alterations seen in tumor cells in men with long-term follow-up after radical prostatectomy (RP). METHODS: NCI Cooperative Prostate Cancer Tissue Resource tissue microarray cores of 92 RP cases (56 non-recurrences and 36 PSA recurrences) were utilized for the study. p300 expression was assessed by quantitative immunohistochemistry and nuclear alterations in Feulgen-stained nuclei were evaluated by digital image analysis using the AutoCyte Pathology Workstation. Cox proportional hazards regression, Spearman's rank correlation, and Kaplan-Meier plots were employed to analyze the data. RESULTS: p300 expression significantly correlated with nuclear alterations seen in tumor cells; specifically with circular form factor (P = 0.012) and minimum feret (P = 0.048). p300 expression in high grade tumors (Gleason score >or=7) was significantly higher compared to low grade tumors (Gleason score <7) [17.7% versus 13.7%, respectively, P = 0.03]. TNM stage, Gleason score, and p300 expression were univariately significant in the prediction of PCa biochemical recurrence-free survival (P <or= 0.05). p300 expression remained significant in the multivariate model (P = 0.03) while Gleason score showed a trend toward significance (P = 0.06). Patients with a Gleason score >or=7 and p300 expression >24% showed the highest risk for PCa biochemical recurrence (P = 0.002). CONCLUSIONS: p300 expression correlates with nuclear alterations seen in tumor cells and has prognostic value in predicting long-term PCa biochemical recurrence-free survival

OBJECTIVES: To determine, by systematic review and meta-analysis of all randomized controlled trials examining ureteral stent placement after ureteroscopy, whether the presence or absence of a stent was associated with postoperative complications. METHODS: All randomized clinical trials of ureteral stent placement after ureteroscopy were identified with PubMed. The primary outcome was the occurrence of a urologic complication, defined as secondary procedure, emergency department evaluation, or hospital admission. The complication rates were compared between the stented (treatment) and unstented (control) arms of each trial as a risk difference, pooled as a weighted average across all studies, using both fixed and random-effects models. RESULTS: Ten trials were identified, with a total of 891 subjects. Patients undergoing ureteral stent placement after ureteroscopy had a 4% lower occurrence of urologic complications (95% confidence interval -10.1%, 1.8%). This difference, however, failed to reach statistical significance after accounting for heterogeneity in the data (P = 0.175). CONCLUSIONS: There is a slightly lower absolute risk of complication associated with the placement of a ureteral stent after ureteroscopy. However, meta-analysis of the present literature does not detect a significant difference in outcome between patients who undergo ureteral stent placement after ureteroscopy and those who do not

PURPOSE: We assessed the use of quantitative clinical and pathologic information to predict which patients would eventually require treatment for prostate cancer (CaP) in an expectant management (EM) cohort. EXPERIMENTAL DESIGN: We identified 75 men having prostate cancer with favorable initial biopsy characteristics; 30 developed an unfavorable biopsy (Gleason grade >6, >2 cores with cancer, >50% of a core with cancer, or a palpable nodule) requiring treatment and 45 maintained favorable biopsies throughout a median follow-up of 2.7 years. Demographic, clinical data and quantitative tissue histomorphometry determined by digital image analysis were analyzed. RESULTS: Logistic regression (LR) modeling generated a quantitative nuclear grade (QNG) signature based on the enrollment biopsy for differentiation of Favorable and Unfavorable groups using a variable LR selection criteria of P(z)<0.05. The QNG signature utilized 12 nuclear morphometric descriptors (NMDs) and had an area under the receiver operator characteristic curve (ROC-AUC) of 87% with a sensitivity of 82%, specificity of 70% and accuracy of 75%. A multivariable LR model combining QNG signature with clinical and pathological variables yielded an AUC-ROC of 88% and a sensitivity of 81%, specificity of 78% and accuracy of 79%. A LR model using prostate volume, PSA density, and number of pre-diagnosis biopsies resulted in an AUC-ROC of 68% and a sensitivity of 85%, specificity of 37% and accuracy of 56%. CONCLUSIONS: QNG using EM prostate biopsies improves the predictive accuracy of LR models based on traditional clinicopathologic variables in determining which patients will ultimately develop an unfavorable biopsy. Our QNG-based model must be rigorously, prospectively validated prior to use in the clinical arena