Stephen A. Boorjian

Anatomic Features of Enhancing Renal Masses Predict Malignant and High-Grade Pathology: A Preoperative Nomogram Using the RENAL Nephrometry Score

BACKGROUNDnCounseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology.nnnOBJECTIVEnWe evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features.nnnDESIGN, SETTING, AND PARTICIPANTSnWe retrospectively queried Fox Chase Cancer Centers prospectively maintained database for consecutive renal masses where a Nephrometry score was available.nnnINTERVENTIONnAll patients in the cohort underwent either partial or radical nephrectomy.nnnMEASUREMENTSnThe individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors.nnnRESULTS AND LIMITATIONSnNephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p < 0.0001) and histology (p < 0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study.nnnCONCLUSIONSnThe current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass.

Preoperative Hydronephrosis, Ureteroscopic Biopsy Grade and Urinary Cytology Can Improve Prediction of Advanced Upper Tract Urothelial Carcinoma

PURPOSEnWe evaluated the value of hydronephrosis, ureteroscopic biopsy grade and urinary cytology to predict advanced upper tract urothelial carcinoma.nnnMATERIALS AND METHODSnWe reviewed the charts of 469 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy or distal ureterectomy. Complete data on hydronephrosis (present vs absent), ureteroscopic grade (high vs low) and urinary cytology (positive vs negative) were available in 172 patients. The outcome was muscle invasive (pT2-pT4) or nonorgan confined (pT3 or greater, or lymph node metastasis) upper tract urothelial carcinoma.nnnRESULTSnOf the patients 92 (54%) had hydronephrosis, 74 (43%) had high grade disease on ureteroscopic biopsy and 137 (80%) had positive cytology. On univariate analysis hydronephrosis (p <0.001), high ureteroscopic grade (p <0.001) and positive cytology (p = 0.03) were associated with muscle invasive and nonorgan confined disease. On multivariate analysis adjusting for tumor site, gender and age hydronephrosis and high ureteroscopic grade were associated with muscle invasive carcinoma (HR 12.0 and 4.5, respectively, each p <0.001) but cytology was not (HR 2.3, p = 0.17). However, all 3 variables were independently associated with nonorgan confined disease (HR 5.1, p <0.001; HR 3.9, p <0.001; and HR 3.1, p = 0.035, respectively). Combining these 3 tests incrementally improved the prediction of upper tract urothelial carcinoma stage. Abnormality of all 3 tests had 89% and 73% positive predictive value for muscle invasive and nonorgan confined upper tract urothelial carcinoma, respectively, but when all tests were normal, the negative predictive value was 100%.nnnCONCLUSIONSnPreoperative evaluation for hydronephrosis, ureteroscopic grade and cytology can identify patients at risk for advanced upper tract urothelial carcinoma. Such knowledge may impact surgery choice and extent as well as the need for perioperative chemotherapy regimens.

Increased Expression of the Polycomb Group Gene, EZH2, in Transitional Cell Carcinoma of the Bladder

Purpose: The Polycomb group gene, EZH2, functions as a transcriptional repressor involved in gene silencing. Amplification of EZH2 has been reported in several malignancies, including prostate, breast, and lymphoma. We evaluated EZH2 mRNA and protein expression in bladder specimens from patients and the EZH2 mRNA expression in five bladder cancer cell lines. Experimental Design:EZH2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR) in 38 bladder tissue specimens. We also evaluated 39 bladder cancer specimens for EZH2 protein expression using immunohistochemistry with affinity-purified antibodies to human EZH2. In addition, five human bladder cancer cell lines were analyzed by RT-PCR for EZH2 mRNA expression. Results: Five of 14 (36%) nontumor bladder specimens versus 21 of 24 (88%) bladder tumors showed EZH2 mRNA expression (P = 0.003). All of the invasive tumors (10 of 10) had detectable EZH2 mRNA expression, compared with 11 of 14 (79%) superficial tumors. In addition, EZH2 mRNA expression was noted in 100% (16 of 16) of high-grade bladder tumors versus 50% (4 of 8) of low-grade tumors (P = 0.01). EZH2 protein expression, meanwhile, was increased in neoplastic tissue compared with nontumor urothelium (78% versus 69% of nuclei, P < 0.005). There were no differences in EZH2 protein levels between superficial and invasive tumors. High-grade tumors had increased EZH2 staining compared with normal urothelium (78% versus 68%, P < 0.005), whereas low-grade lesions did not. Four of five human bladder cancer cell lines expressed high levels of EZH2, whereas only low levels were detected in one cell line. Conclusions: We report a significant increase in EZH2 expression in transitional cell carcinoma of the bladder compared with normal urothelium. These data suggest that similar to other human malignancies, increased EZH2 expression correlates with oncogenesis of the bladder.

Natural history, growth kinetics, and outcomes of untreated clinically localized renal tumors under active surveillance

The growth kinetics of untreated solid organ malignancies are not defined. Radiographic active surveillance (AS) of renal tumors in patients unfit or unwilling to undergo intervention provides an opportunity to quantify the natural history of untreated localized tumors. The authors report the radiographic growth kinetics of renal neoplasms during a period of surveillance.

Robot-assisted partial nephrectomy: a large single-institutional experience.

OBJECTIVESnTo report experience with 100 robot-assisted partial nephrectomy (RAPN) operations performed at our institution. Nephron-sparing surgery is an established treatment for patients with small renal masses. The laparoscopic approach has emerged as an alternative to open nephron-sparing surgery, but it is recognized to be technically challenging. The robotic surgical system may enable faster and greater technical proficiency, facilitating a minimally invasive approach to more difficult lesions while reducing ischemia time.nnnMETHODSnA total of 100 RAPN operations were performed for suspicious solid renal lesions during a 21-month period. Clinicopathologic variables, nephrometry scores, operative parameters, and renal functional outcomes were prospectively recorded and analyzed.nnnRESULTSnMedian tumor size was 2.8 cm (range, 1.0-8). Nephrometry scores of resected lesions were low in 47.9% of patients, medium in 45.7%, and high in 6.4% of patients. Forty-seven percent of patients had tumors>50% intraparenchymal, and 61.7% had tumors located less than 7 mm away from the renal sinus or collecting system. In 17% of patients, the tumors were touching a first-order vessel in the renal hilum. Mean warm ischemia time was 25.5 minutes (range, 0-53). Mean change in postoperative glomerular filtration rate improved 6.32 mL/min/1.73 m2 (range, -41.9 to 68.9). Histology was renal cell carcinoma in 81% (87/107) of tumors. There were 5 microscopically positive margins on final pathology (5.7%). Major and minor complication rates were 6% and 5%, respectively. There were 2 conversions to open surgery.nnnCONCLUSIONSnRAPN seems to be a safe and technically feasible minimally invasive approach to nephron-sparing surgery even in more complex cases, with acceptable pathologic and renal function outcomes.

Bladder cancer after managing upper urinary tract transitional cell carcinoma: predictive factors and pathology

To evaluate patients with a history of transitional cell carcinoma (TCC) of the upper urinary tract (UUT) to determine the incidence, pathological distribution, and risk factors for developing subsequent bladder tumours.

The Impact of Positive Surgical Margins on Mortality Following Radical Prostatectomy During the Prostate Specific Antigen Era

PURPOSEnThe presence of a positive surgical margin at radical prostatectomy has been linked to an increased risk of postoperative biochemical recurrence. We evaluated the impact of margin status on subsequent clinical progression and mortality.nnnMATERIALS AND METHODSnWe reviewed the records of 11,729 patients who underwent prostatectomy between 1990 and 2006. Survival was estimated for patients with vs without a positive margin and compared using the log rank test. Cox proportional hazards regression models were used to analyze the impact of margin status on survival.nnnRESULTSnOverall 3,651 (31.1%) men were identified with a positive margin. Median postoperative followup was 8.2 years (IQR 4.4, 12.1). The 10-year biochemical recurrence-free rate for patients with and without a positive margin was 56% and 77%, respectively (p <0.001), while 10-year local recurrence-free survival was 89% vs 95% (p <0.001). Margin status also stratified systemic progression-free survival (93% vs 97%, p <0.001), cancer specific survival (96% vs 99%, p <0.001) and overall survival (83% vs 88%, p <0.001). On multivariate analysis the presence of a positive margin was associated with increased risk of biochemical recurrence (HR 1.63, 95% CI 1.47-1.80, p <0.0001), local recurrence (HR 1.78, 95% CI 1.45-2.19, p <0.0001) and receipt of salvage therapy (HR 1.79, 95% CI 1.58-2.02, p <0.0001) but was not a significant predictor of systemic progression (p = 0.95), cancer specific death (p = 0.15) or overall mortality (p = 0.16).nnnCONCLUSIONSnThe presence of a positive margin increased the risk of biochemical recurrence, local recurrence and the need for salvage treatment but was not independently associated with systemic progression, cancer specific death or overall mortality. These results should be considered when evaluating patients for adjuvant therapy.

Urinary cytology has a poor performance for predicting invasive or high‐grade upper‐tract urothelial carcinoma

Study Type – Therapy (case series)

Radiation Therapy After Radical Prostatectomy: Impact on Metastasis and Survival

PURPOSEnAlthough secondary radiation therapy decreases the risk of biochemical progression after radical prostatectomy, its impact on metastasis and survival is less well established. We evaluated the impact of adjuvant and salvage radiotherapy on clinical progression and mortality.nnnMATERIALS AND METHODSnA total of 361 patients who received adjuvant radiation were matched based on clinicopathological features to patients who did not receive adjuvant radiation in a 2:1 case-control ratio. Postoperative survival was estimated using the Kaplan-Meier method and compared using the log rank test. A second cohort of 2,657 men who experienced biochemical recurrence after prostatectomy was separately evaluated. Cox proportional hazard regression models were used to analyze the impact of salvage radiotherapy on disease progression and survival.nnnRESULTSnAdjuvant radiotherapy was associated with significantly improved 10-year biochemical recurrence-free survival (63% vs 45%, p <0.001), local recurrence-free survival (97% vs 82%, p <0.001) and a decreased need for late hormone therapy (17% vs 28%, p = 0.002) but did not impact systemic progression and overall survival (p = 0.94 and 0.27, respectively). Of the 2,657 patients who experienced biochemical recurrence after surgery 856 (32.3%) received salvage radiation. On multivariate analysis salvage radiotherapy decreased the risk of local recurrence (HR 0.13, 95% CI 0.06-0.28, p <0.0001) and delayed hormonal therapy (HR 0.81, 95% CI 0.71-0.93, p = 0.003) and systemic progression (HR 0.24, 95% CI 0.13-0.45, p <0.0001) but did not significantly impact mortality (p = 0.48).nnnCONCLUSIONSnAdjuvant and salvage radiation provide long-term local control and decrease the need for delayed hormonal therapy but neither improves survival. These results must be weighed against the potential morbidity of postoperative radiation when counseling patients.

Baseline Renal Function Status Limits Patient Eligibility to Receive Perioperative Chemotherapy for Invasive Bladder Cancer and Is Minimally Affected by Radical Cystectomy

OBJECTIVESnTo evaluate the proportion of patients with muscle-invasive urothelial carcinoma (UC) who would be eligible to receive cisplatin-based chemotherapy before and after radical cystectomy based on renal function.nnnMETHODSnWe identified 194 consecutive patients who underwent cystectomy for cT2-T4 UC. Serum creatinine (SCr) immediately before and nadir SCr 1-3 months after surgery were used to calculate creatinine clearance (CrCl) and glomerular filtration rate (GFR). A cut-off CrCl ≥ 60 mL/min or GFR ≥ 60 mL/min/1.73 m(2) was used to determine eligibility for chemotherapy.nnnRESULTSnMedian patient age was 70.5 years (IQR 63.77) and median preoperative SCr was 1.05 mg/dL (0.9, 1.3). In total, 80/194 (41%) and 64/194 (33%) patients had inadequate renal function to receive chemotherapy before cystectomy based on CrCl and GFR, respectively. The frequency of inadequate baseline renal function increased significantly with patient age, from 12% of patients < 65 to 54% of patients >65 years of age (P < 0.0001). Surgery did not adversely affect the proportion of patients eligible to receive chemotherapy based on renal function, regardless of age. In fact, after controlling for gender, race, preoperative renal function, hydronephrosis, and choice of diversion, patients <65 years of age were found to have a 14% increase in CrCl (P = .01) and an 11% increase in GFR (P = .04) after cystectomy.nnnCONCLUSIONSnApproximately 40% of patients who would be candidates for neoadjuvant chemotherapy could not receive cisplatin because of poor renal function. Surgery did not affect patients eligibility to receive chemotherapy based on renal function status. Development of effective non-cisplatin-based regimens is therefore necessary to optimize survival.