Thomas J. Guzzo

Impact of surgical technique (open vs laparoscopic vs robotic-assisted) on pathological and biochemical outcomes following radical prostatectomy: an analysis using propensity score matching

Study Type – Therapy (case series)

Long-term Survival After Radical Prostatectomy for Men With High Gleason Sum in Pathologic Specimen

OBJECTIVES To evaluate the long-term outcomes of patients with high Gleason sum 8-10 at radical prostatectomy (RP) and to identify the predictors of prostate cancer-specific survival (CSS) in this cohort. METHODS The institutional RP database was queried. A total of 9381 patients with complete follow-up underwent RP from 1982 to 2008. Of these 9381 patients, 1061 had pathologic Gleason sum 8-10 cancer. The patient and prostate cancer characteristics were evaluated. Survival analyses were performed using the Kaplan-Meier method. Univariate and multivariate proportional hazard regression models were created to evaluate the pertinent predictors of CSS (death from, or attributed to, prostate cancer). RESULTS The median preoperative prostate-specific antigen level was 7.6 ng/mL; 435 men had clinical Stage T1 tumor, 568 had Stage T2, and 36 had Stage T3. The biopsy Gleason sum was <7, 7, and >7 in 244 (22.3%), 406 (37.2%), and 425 (38.9%) patients, respectively. The median follow-up was 5 years (range 1-23). The actuarial 15-year recurrence-free survival, CSS, and overall survival rate was 20.7%, 57.4%, and 45.4%, respectively. On multivariate analysis, the predictors of poor CSS were pathologic Gleason sum 9-10 and seminal vesicle and lymph node involvement. Patients with pathologic Gleason sum 8 and organ-confined disease had a CSS rate of 89.9% at 15 years. CONCLUSIONS The results of our study have shown that 80% of the men with Gleason sum 8-10 who undergo RP will have experienced biochemical recurrence by 15 years. However, the CSS rate approached 90% for men with pathologic organ-confined disease. Higher pathologic Gleason sum 9-10 and seminal vesicle and lymph node involvement were independent predictors of worse CSS.

Prediction of Mortality After Radical Prostatectomy by Charlson Comorbidity Index

OBJECTIVES Prostate cancer treatment should depend on the characteristics of a patients prostate cancer as well as overall health status. A possible adverse consequence of poor patient selection is a lack of benefit because of premature death from another cause. We evaluated the association between perioperative comorbidity and risk of death from causes other than prostate cancer in men who underwent radical prostatectomy (RP). METHODS We conducted a retrospective cohort study of 14,052 men who underwent RP from 1983 to 2006. The Charlson Comorbidity Index (CCI) score was calculated using the discharge records for the prostatectomy hospitalization. Mortality status and cause of death were obtained via chart review and searches of national databases. Cox proportional hazards regression was used to estimate the hazard ratio (HR) of death from causes other than prostate cancer after RP by CCI score (0, 1, 2+). RESULTS The median age at RP was 58.1 years. The median follow-up was 7.6 years (interquartile range 4.3-11.5). Of 849 deaths, 599 (70.6%) resulted from causes other than prostate cancer. On multivariable analysis, men with a CCI ≥2 had a statistically significantly higher risk of death from causes other than prostate cancer compared with those with lower CCI scores (HR 2.18, 95% CI 1.30-3.64, P = .0003). CONCLUSIONS Greater perioperative comorbidity was associated with a higher risk of death from causes other than prostate cancer in men who underwent RP. Physicians should consider using a standardized tool to assess perioperative comorbidities to enhance appropriate recommendation for surgical treatment.

Incidentally discovered renal masses: oncological and perioperative outcomes in patients with delayed surgical intervention.

To evaluate whether a period of surveillance before laparoscopic partial nephrectomy (LPN) affects the pathological and clinical outcomes of patients with a small renal mass, as although the standard treatment for an enhancing renal mass remains surgical extirpation, surveillance of small renal masses has become a potential option in appropriately selected patients.

Bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC): a review of the literature and a practical approach to therapy.

Bladder preservation therapies for muscle‐invasive bladder cancer (MIBC) have been developed to address the needs of two cohorts: patients with severe medical co‐morbidities for whom radical cystectomy is too high risk and patients with limited disease who wish to avoid aggressive surgery. There are multiple bladder preservation options, although the trimodal approach of maximal transurethral resection with chemoradiotherapy is the most strongly supported. While outcomes are worse for patients unfit for surgery than those otherwise fit for surgery, bladder preservation approaches still offer curative potential.

The presence of circulating tumor cells does not predict extravesical disease in bladder cancer patients prior to radical cystectomy

OBJECTIVE Due to imprecise clinical staging, the finding of extravesical and node-positive disease at the time of radical cystectomy (RC) for patients with clinically localized bladder cancer is not uncommon. Circulating tumor cells (CTCs) have been shown to be present in the peripheral blood of patients with metastatic urothelial carcinoma. The object of this study was to evaluate the ability of CTCs to predict extravesical disease in bladder cancer patients prior to RC. MATERIALS AND METHODS Peripheral blood samples from 43 patients with bladder cancer were evaluated using the CellSearch (Veridex, LLC, Raritan, NJ) CTC assay prior to RC. The sensitivity, specificity, and positive predictive value (PPV) of CTC status in predicting extravesical disease was calculated. Receiver operating characteristic (ROC) curves were generated to quantify the ability of CTCs to predict extravesical and node-positive disease. RESULTS CTCs were detected in 9 (21%) patients prior to RC. The sensitivity, specificity, and PPV of CTC status in predicting extravesical disease were 27%, 88% and 78%, respectively. The accuracy of CTC status in predicting extravesical (≥pT3 or node-positive) disease for the entire cohort was 0.576. In a model incorporating preoperative hydronephrosis, CTC status did not improve the predictive accuracy for extravesical disease (0.576 vs. 0.585, P = 0.915). CONCLUSION CTCs were detected in low numbers in a small percentage (21%) of patients prior to undergoing RC at our institution. CTC status was not a robust predictor of extravesical or node-positive disease in this cohort. CTC status is not likely to be a clinically useful parameter for directing therapeutic decisions in patients with ≤cT2 bladder cancer.

Optimizing bladder cancer locoregional failure risk stratification after radical cystectomy using SWOG 8710.

Clinical trials of radiation after radical cystectomy (RC) and chemotherapy for bladder cancer are in development, but inclusion and stratification factors have not been clearly established. In this study, the authors evaluated and refined a published risk stratification for locoregional failure (LF) by applying it to a multicenter patient cohort.

Longitudinal evaluation of the concordance and prognostic value of lymphovascular invasion in transurethral resection and radical cystectomy specimens.

THIS IS A COMMENT MODERATED PAPER
available at http://www.bjui.org/commentary

Increased EZH2 protein expression is associated with invasive urothelial carcinoma of the bladder

OBJECTIVES Elevated polycomb group protein Enhancer of Zest Homolog 2 (EZH2) expression has been associated with progression to more advanced disease in a variety of malignancies. We examined EZH2 protein expression levels in bladder tissue specimens from patients with urothelial carcinoma (UC) and investigated the relationship between EZH2 protein expression and clinical outcomes. MATERIALS AND METHODS Tissue microarrays (TMAs) were constructed using bladder tissue specimens from radical cystectomies performed for UC at our institution between 1994 and 2002. EZH2 expression was measured by immunohistochemistry and scoring was based on percentage and intensity of positive nuclear staining. A receiver operating curve (ROC) was generated to differentiate cancerous from benign lesions using EZH2 protein scores. Recurrence-free survival was estimated using the Kaplan-Meier approach with log-rank test. A multivariate Cox proportional hazards model was used to assess independent contributions. RESULTS A total of 454 TMA specimen spots from 81 patients were evaluated. EZH2 protein levels in invasive high grade UC were significantly elevated compared with adjacent benign urothelium, noninvasive low grade UC, and CIS. EZH2 protein levels were also significantly increased in CIS and noninvasive low grade UC compared with adjacent benign urothelium. We found no association between EZH2 protein expression and clinical outcomes following radical cystectomy in our cohort of patients. CONCLUSION EZH2 overexpression is a common event in UC of the bladder. Elevated EZH2 protein levels are associated with more aggressive bladder cancer, including invasive UC. EZH2 may therefore serve as a useful biomarker for UC.

Bladder Cancer Patterns of Pelvic Failure: Implications for Adjuvant Radiation Therapy

PURPOSE Local-regional failures (LFs) after cystectomy with or without chemotherapy are common in locally advanced disease. Adjuvant radiation therapy (RT) could reduce LFs, but toxicity has discouraged its use. Modern RT techniques with improved normal tissue sparing have rekindled interest but require knowledge of pelvic failure patterns to design treatment volumes. METHODS AND MATERIALS Five-year LF rates after radical cystectomy plus pelvic node dissection with or without chemotherapy were determined for 8 pelvic sites among 442 urothelial bladder carcinoma patients. The impact of pathologic stage, margin status, nodal involvement, and extent of node dissection on failure patterns was assessed using competing risk analysis. We calculated the percentage of patients whose sites of LF would have been completely encompassed within various hypothetical clinical target volumes (CTVs) for postoperative radiation. RESULTS Compared with stage ≤pT2, stage ≥pT3 patients had higher 5-year LF rates in virtually all pelvic sites. Among stage ≥pT3 patients, margin status significantly altered the failure pattern whereas extent of node dissection and nodal positivity did not. In stage ≥pT3 patients with negative margins, failure occurred predominantly in the iliac/obturator nodes and uncommonly in the cystectomy bed and/or presacral nodes. Of these patients in whom failure subsequently occurred, 76% would have had all LF sites encompassed within CTVs covering only the iliac/obturator nodes. In stage ≥pT3 with positive margins, cystectomy bed and/or presacral nodal failures increased significantly. Only 57% of such patients had all LF sites within CTVs limited to the iliac/obturator nodes, but including the cystectomy bed and presacral nodes in the CTV when margins were positive increased the percentage of LFs encompassed to 91%. CONCLUSIONS Patterns of failure within the pelvis are summarized to facilitate design of adjuvant RT protocols. These data suggest that RT should target at least the iliac/obturator nodes in stage ≥pT3 with negative margins; coverage of the presacral nodes and cystectomy bed may be necessary for stage ≥pT3 with positive margins.