Faculty Bibliography

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

PURPOSE: Laparoscopic urinary diversion remains difficult and time consuming even when performed by experienced laparoscopists. Here we describe a novel procedure that quickly creates an ileal orthotopic neobladder with an afferent tubular segment using a laparoscopic stapling device. MATERIALS AND METHODS: Laparoscopic cystectomy and stapled ileal neobladder were performed in five domestic juvenile pigs. Following cystectomy, 30 to 40 cm of terminal ileum was harvested, and ileal continuity restored. The harvested ileum was made into a J configuration, and three to seven laparoscopic staple firings were used to create a spherical pouch with an afferent limb modeled after the Studer-type neobladder. An aperture was created in the dependent portion of the neobladder, and urethral anastomosis was performed using six interrupted absorbable sutures. Ureterointestinal anastomosis was performed using a Wallace technique. Postoperative cystography and intravenous pyelography were performed. A 1-month survival study was completed in one pig. RESULTS: All five procedures were completed successfully without conversion to open surgery. The majority of the steps of the procedures were performed by second- and third-year urology residents (PGY 3-4). Neobladder stapling, ureterointestinal anastomosis, and the first three urethral sutures were performed by an endourology fellow. Average time for neobladder creation and entire procedure was 78 and 355 minutes, respectively. Postoperative cystography revealed spherical orthotopic neobladder with minimal or no leakage in all animals. Average neobladder capacity was 100 mL, and no obstruction was visualized on intravenous pyelography immediately after the procedures. One pig successfully survived the 1-month study period. There was excellent neobladder storage, no clinically apparent renal obstruction, and no postoperative complications. CONCLUSIONS: Total laparoscopic urinary diversion and specifically orthotopic neobladder remains one of the frontiers of minimally invasive urologic surgery. Our technique for stapled ileal neobladder provides substantial advantages in terms of the operative time required for orthotopic neobladder reconstruction. This may offer an avenue to foster the development of more feasible techniques for laparoscopic urinary tract reconstructive surgery

BACKGROUND: Nuclear morphometric signatures can be calculated using nuclear size, shape, DNA content, and chromatin texture descriptors [nuclear morphometric descriptor (NMD)]. We evaluated the use of a patient-specific quantitative nuclear grade (QNG) alone and in combination with routine pathologic features to predict biochemical [prostate-specific antigen (PSA)] recurrence-free survival in patients with prostate cancer. METHODS: The National Cancer Institute Cooperative Prostate Cancer Tissue Resource (NCI-CPCTR) tissue microarray was prepared from radical prostatectomy cases treated in 1991 to 1992. We assessed 112 cases (72 nonrecurrences and 40 PSA recurrences) with long-term follow-up. Images of Feulgen DNA-stained nuclei were captured and the NMDs were calculated using the AutoCyte system. Multivariate logistic regression was used to calculate QNG and pathology-based solutions for prediction of PSA recurrence. Kaplan-Meier survival curves and predictive probability graphs were generated. RESULTS: A QNG signature using the variance of 14 NMDs yielded an area under the receiver operator characteristic curve (AUC-ROC) of 80% with a sensitivity, specificity, and accuracy of 75% at a predictive probability threshold of > or =0.39. A pathology model using the pathologic stage and Gleason score yielded an AUC-ROC of 67% with a sensitivity, specificity, and accuracy of 70%, 50%, and 57%, respectively, at a predictive probability threshold of > or =0.35. Combining QNG, pathologic stage, and Gleason score yielded a model with an AUC-ROC of 81% with a sensitivity, specificity, and accuracy of 75%, 78%, and 77%, respectively, at a predictive probability threshold of > or =0.34. CONCLUSIONS: PSA recurrence is more accurately predicted using the QNG signature compared with routine pathology information alone. Inclusion of a morphometry signature, routine pathology, and new biomarkers should improve the prognostic value of information collected at surgery

PURPOSE: We report on the natural history and factors influencing the prognosis of a cohort of hormone naive, prostate specific antigen era patients in whom metastatic prostate cancer developed after radical prostatectomy who were followed closely and treated with deferred androgen deprivation therapy at the time of metastasis. MATERIALS AND METHODS: A total of 3,096 men underwent radical prostatectomy performed by a single surgeon at Johns Hopkins Hospital between 1987 and 2005. Of these men 422 had prostate specific antigen failure. Distant metastasis developed in 123 patients, of whom 91 with complete data formed the study cohort initially treated during the prostate specific antigen era (1987 to 2005) and receiving androgen deprivation therapy after documented metastasis. A total of 41 men died of prostate cancer. Median survival times were estimated by Kaplan-Meier analysis. Prognostic impact was estimated as the hazard ratio derived from the Cox proportional hazards model. RESULTS: Median followup from radical prostatectomy was 120 months (range 24 to 216). Kaplan-Meier median (range) times to failure were 24 months (12 to 144) from radical prostatectomy to prostate specific antigen failure, 36 months (0 to 132) from prostate specific antigen failure to metastasis, 84 months (12 to 180) from metastasis to death and 168 months (24 to 216) from radical prostatectomy to death. Statistically significant univariate risk factors for prostate cancer specific mortality at the time of metastasis were pain at diagnosis of metastases (p = 0.002), time from radical prostatectomy to metastasis (p = 0.024) and prostate specific antigen doubling time less than 3 months during the 24 months before metastasis (p = 0.016). Multivariable analysis demonstrated independent predictors of prostate cancer specific mortality at the time of metastasis, namely pain (HR 3.5, p = 0.003) and prostate specific antigen doubling time less than 3 months (HR 3.4, p = 0.017). CONCLUSIONS: Men treated with deferred androgen deprivation therapy for the development of metastasis after radical prostatectomy may have a long life span, 169 months after radical prostatectomy (range 24 to 216). The presence of pain and short prostate specific antigen doubling time predicted an unfavorable outcome