Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications

ABSTRACT Upper tract urothelial carcinoma (UTUC) is a rare and aggressive disease that is associated with high rates of recurrence and death. Radical nephroureterectomy (RNU) with excision of the bladder cuff is considered the standard of care for high-risk UTUC, whereas kidney-sparing techniques can be indicated for select patients with low-risk disease. There is a significant lack of clinical and pathological prognostic factors for stratifying patients with regard to making treatment decisions. Incorporation of tissue-based molecular markers into prognostic tools could help accurately stratify patients for clinical decision-making in this heterogeneous disease. Although the number of studies on tissue-based markers in UTUC has risen dramatically in the past several years—many of which are based on single centers and small cohorts, with a low level of evidence—many discrepancies remain between their results. Nevertheless, certain biomarkers are promising tools, necessitating prospective multi-institution studies to validate their function.

Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications.

Upper tract urothelial carcinoma (UTUC) is a rare and aggressive disease that is associated with high rates of recurrence and death. Radical nephroureterectomy (RNU) with excision of the bladder cuff is considered the standard of care for high-risk UTUC, whereas kidney-sparing techniques can be indicated for select patients with low-risk disease. There is a significant lack of clinical and pathological prognostic factors for stratifying patients with regard to making treatment decisions. Incorporation of tissue-based molecular markers into prognostic tools could help accurately stratify patients for clinical decision-making in this heterogeneous disease. Although the number of studies on tissue-based markers in UTUC has risen dramatically in the past several years-many of which are based on single centers and small cohorts, with a low level of evidence-many discrepancies remain between their results. Nevertheless, certain biomarkers are promising tools, necessitating prospective multi-institution studies to validate their function.

Prognostic role of decreased E-cadherin expression in patients with upper tract urothelial carcinoma: a multi-institutional study.

PURPOSE: To assess the role of E-cadherin as prognostic biomarker in upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients. METHODS: Immunohistochemistry technique was used to evaluate E-cadherin expression in 678 patients with unilateral, sporadic UTUC treated with RNU. E-cadherin expression was considered decreased if 10 % or more cells had decreased expression (<90 %). RESULTS: Decreased E-cadherin expression was observed in 353 patients (52.1 %) and was associated with advanced pathological stage (P < 0.001), higher grade (P < 0.001), lymph node metastasis (P = 0.006), lymphovascular invasion (P < 0.001), concomitant carcinoma in situ (P < 0.001), multifocality (P = 0.004), tumor necrosis (P = 0.020) and sessile architecture (P < 0.001). Within a median follow-up of 30 months (interquartile range 15-57), 171 patients (25.4 %) experienced disease recurrence and 150 (21.9 %) died from UTUC. In univariable analyses, decreased E-cadherin expression was significantly associated with worse recurrence-free survival (P < 0.001) and cancer-specific survival CSS (P = 0.006); however, in multivariable analyses, it was not (P = 0.74 and 0.84, respectively). The lack of independent prognostic value of E-cadherin remained true in all subgroup analyses. CONCLUSION: In UTUC patients treated with RNU, decreased E-cadherin expression is associated with features of biologically and clinically aggressive disease and worse outcome in univariable, but not multivariable, analyses. If E-cadherin's association with factors of advanced disease is confirmed on UTUC biopsy specimens, it could be used to help in the clinical decision-making regarding kidney-sparing approaches and/or neo-adjuvant chemotherapy.

Predictors of cancer-specific mortality after disease recurrence in patients with squamous cell carcinoma of the penis.

Disease recurrence occurs frequently after surgical treatment for squamous cell carcinoma of the penis (SCCp). We sought to determine prognostic factors that influence cancer-specific mortality (CSM) after disease recurrence in patients with SCCp. We performed a retrospective analysis of 314 patients who experienced disease recurrence after surgical treatment for SCCp between 1949 and 2012. Competing risk regression analysis addressed factors associated with CSM after SCCp recurrence. Median time from surgery to disease recurrence was 10.5 mo (interquartile range [IQR]: 5.9-21.3). Of the recurrences, 165 (53%), 118 (38%), and 31 (9.9%) were local, regional, or distant, respectively. Within a median follow-up of 4.5 yr (IQR: 2.0-6.5), 108 patients died of SCCp and 41 patients died of causes other than SCCp. Shorter time to disease recurrence was found to be significantly associated with a higher risk of CSM (p=0.0006). Lymph node metastasis at the time of initial treatment (subdistribution hazard ratio [SHR]: 1.96; 95% confidence interval [CI] 1.23- 3.11; p=0.005) and regional recurrence (SHR: 4.14; 95% CI, 2.16-7.93; p<0.0001) or distant recurrence (SHR: 5.75; 95% CI, 2.59-12.73; p<0.0001) were associated with increased risk of CSM after disease recurrence. Inclusion of time to recurrence into risk stratification may help patient counseling and treatment planning.

Use of a hyaluronic acid-carboxymethylcellulose adhesion barrier on the neurovascular bundle and prostatic bed to facilitate earlier recovery of erectile function after robot-assisted prostatectomy: an initial experience.

PURPOSE: To investigate the efficacy of hyaluronic acid-carboxymethylcellulose (HACM) in facilitating early recovery of erectile function (EF) after radical prostatectomy, we report our initial experience of HACM use on the neurovascular bundle (NVB) after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Between 2008 and 2010, 459 consecutive patients who underwent RARP with bilateral nerve-sparing technique were included in this study. Patients were classified into two groups: HACM (group 1; n=162) and non-HACM (group 2; n=287). HACM was delivered to the anatomic location of the NVB after prostate removal. We retrospectively analyzed the surgical outcomes including EF, continence, and perioperative complications. RESULTS: At 6 months after surgery, EF recovery rate was 28.5% in group 1 and 17.4% in group 2 (P=0.006). In a subgroup analysis consisting of 225 patients with a preoperative International Index of Erectile Function Short Survey (IIEF)-5 score ≥20, the difference in EF recovery at 6 months was significant with 62.8% in group 1 and 27.0% in group 2 (P=0.002), respectively. HACM use was an independent predictor for EF recovery at 6 months after surgery (odds ratio, 2.735; 95% confidence interval, 1.613-4.638; P<0.001). Age and preoperative IIEF-5 were also independent predictors. No differences in continence at 6 months or perioperative complications were found between the two groups. EF recovery was not different between the two groups after 18 months. CONCLUSIONS: HACM use around the NVBs is safe and facilitates early recovery of EF after nerve-sparing RARP. HACM use is more effective in patients with normal preoperative sexual function.

The impact of immunohistochemical expression of nitric oxide synthases on clinical and pathological features of renal cell carcinoma.

PURPOSE: To evaluate the immunohistochemical expression of nitric oxide synthase (NOS) types 1, 2, and 3 in intratumoral and non-neoplastic samples of renal cell carcinoma (RCC) and correlate it with the clinical and pathological features of this malignancy. METHODS: We analyzed 110 patients with RCC underwent radical nephrectomy (RN) or partial nephrectomy (PN) by streptavidin-biotin peroxidase method, tissue microarray, and digital microscopy. As endpoints, NOS expression was correlated with pathological features, overall survival (OS), and cancer-specific survival (CSS). RESULTS: Non-neoplastic samples had higher NOS3 and lower NOS 2 levels than RCC tissues. Greater expression of all NOS isoforms was associated with larger tumors. High NOS1 expression correlated with microscopic venous invasion (MVI) (p = 0.046) and lymph node metastases (p = 0.007). High NOS2 expression was linked to MVI, more RN performed, and male gender (p = 0.035, p = 0.003, and p = 0.027, respectively). High NOS3 expression correlated with lymph node metastases (p = 0.039), microlymphatic invasion (p = 0.029), invasion of the renal pelvis and ureter (p = 0.004), RN (p = 0.003), and shorter OS (58.1 vs. 79.4 % respectively, p = 0.033) by univariate analysis. DFS was not influenced by any NOS isoform. By multivariate analysis, the risk factors for death were TNM stages III and IV (hazard ratio [HR] = 4.5), high Fuhrman's grade (HR = 2.9), Karnofsky performance status ≤80 (HR = 2.5), progression (HR = 5.5), and recurrence (HR = 6.3). Stage III disease was an independent risk factor for recurrence (HR = 9.5). CONCLUSIONS: High NOS expression in RCC is associated with a poor prognosis and larger tumors. NOS3 influences OS by univariate analysis.

Oncologic outcomes after laparoscopic partial nephrectomy: mid-term results.

INTRODUCTION: To describe the oncologic outcomes of renal cell carcinoma (RCC) diagnosed in patients and submitted to laparoscopic partial nephrectomy (LPN) in a laparoscopic referral center. PATIENTS AND METHODS: We retrospectively analyzed data of 150 consecutive patients with small renal masses and treated with LPN between 2000 and 2010 at a laparoscopic referral center. Pathologic RCC was diagnosed in 137 patients and were included in the oncologic outcome analysis. Kaplan-Meyer methods were used to estimate the probability of disease recurrence and cancer-specific survival. RESULTS: Median follow-up for patients without recurrence was 38 months (interquartile range [IQR] 19-70). The majority of the patients (88%) were found to have pT1a disease at the final pathology report; eight patients (6%) were classified as pT3a. The median tumor size was 25 mm (IQR 20-32). Clear cell type histology was found in 97 patients (66%); most of the patients had Fuhrman grade 2 (72%) or 3 (21%). The 2- and 5-year recurrence-free survival rates were 98% and 95%, respectively. The positive surgical margin was found in 1.4% of the patients. The 2-year and 5-year CSS rates were 99% and 97%, respectively. Kaplan-Meyer methods showed that patients with pT3a were more likely to experience disease recurrence and patients with Fuhrman grade 3 to die of the disease. CONCLUSIONS: LPN seems to provide excellent cancer control rates and to be an oncologically feasible and safe option for treating patients with small renal masses. Recurrence and death from the disease are extremely uncommon and mostly related to a higher pathologic stage or Fuhrman grade, but not positive surgical margins.

Systematic classification and prediction of complications after nephrectomy in patients with metastatic renal cell carcinoma (RCC).

UNLABELLED: Study Type - Harm (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Radical nephrectomy for patients with metastatic renal cell carcinoma results in greater rates of morbidity than for those with less advanced disease. This study systematically characterizes complications associated with nephrectomy for metastatic RCC and identifies patient and disease characteristics that are associated with a greater risk of developing complications. Overall complications were relatively frequent, but major complications (grade 3 or greater) were rare. Increasing age and worsening performance status were associated with increased probability of complications. When complications were sustained, patients were less likely to receive systemic therapy in a timely fashion. These observations may influence the timing or patient selection for surgery or systemic therapy. OBJECTIVE: • To evaluate and identify factors predictive for morbidity after radical nephrectomy in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: • We identified patients with mRCC who underwent nephrectomy at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1989 and 2009. • Postoperative complications were characterised using a modified version of the Clavien-Dindo classification system. • Patient and disease characteristics, including a previously validated MSKCC risk-stratification system using calcium, haemoglobin (Hb), lactate dehydrogenase, and Karnofsky Performance Status (KPS), were evaluated as predictors of postoperative complications using univariate and multivariable logistic regression models. • The area under the receiver operating characteristic curve (AUC) was calculated for each model to assess predictive accuracy and corrected for overfit using 10-fold cross validation. RESULTS: • Over the study period, 195 patients with mRCC underwent nephrectomy; 53 (27%) developed grade ≥ 2 complications within 8 weeks of surgery. • Pulmonary, thromboembolic events and anaemia requiring transfusion were the most common types of complications after nephrectomy in the metastatic setting. • In univariate analysis, age, low albumin, low KPS, high corrected serum calcium, low serum Hb, and unfavourable MSKCC risk score were predictive of complications. • Patients who sustained postoperative complications were less likely to receive systemic therapy within 56 days (odds ratio [OR] 0.32; 95% confidence interval [CI] 0.12-0.86; P= 0.024). • A multivariable model containing KPS (OR 14.5; 95%CI 4.34-48.6; P < 0.001) and age (OR 1.04; 95%CI 1.01-1.08; P= 0.014) showed the greatest predictive accuracy (corrected AUC 0.72; 95%CI 0.63-0.80) for postoperative complications. CONCLUSIONS: • Postoperative complications after radical nephrectomy in the setting of mRCC are common and occur frequently in older patients and those with worse KPS. • These complications are important because they may delay or deny receipt of subsequent systemic therapy.

Bilateral testicular germ cell tumours: a systematic review.

What's known on the subject? and What does the study add? Bilateral testicular germ cell tumours (BTGCTs) are rare neoplasms. Most previously published studies consist of case reports or small retrospective case series. Little is known about their epidemiological and clinicopathological characteristics. BTGCT corresponded to 1.82% of testicular tumours. Metachronous disease was about twice as frequent as synchronous disease. The primary tumour histology, chemotherapy use and the interval between metachronous tumours influenced the histology of the second tumour. Overall, synchronous tumours were associated with more advanced disease and presented less favourable survival rates than metachronous tumours. Testicular cancer is the most common tumour in young men. It is known that a second primary contralateral testis tumour may occur in up to 5% of men with a proior tumour. About 35% of these men present with synchronous tumours, and 65% present with metachronous tumours. However there is little data about bilateral testicular germ cell tumours (BTGCT) in the literature and the most published articles are case reports on a small series of men, which makes it difficult to draw conclusions about therapeutic strategies for the treatment of BTGCTs. In fact, current guidelines for the treatment of testicular cancer contain little information related to bilateral disease. Therefore, the aim of our study is to provide a broad overview of BTGCT and to update data focusing on incidence, pathological features, and clinical outcomes of men with BTGCTs. Thus, an extensive review containing 94 studies and more than 50,000 patients was conducted.

Renal function and oncologic outcomes of parenchymal sparing ureteral resection versus radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: We compared renal function and oncologic outcomes of parenchymal sparing ureteral resection with radical nephroureterectomy for the treatment of upper tract urothelial carcinoma confined to the ureter. MATERIALS AND METHODS: Review of a large institutional database identified 367 patients treated for primary upper tract urothelial carcinoma with radical nephroureterectomy or parenchymal sparing ureteral resection from 1994 to 2009. Patients with known renal pelvis tumors, muscle invasive urothelial carcinoma, prior cystectomy, contralateral upper tract urothelial carcinoma, metastatic disease or chemotherapy were excluded, leaving 120 patients for analysis. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation. Recurrence-free, cancer specific and overall survival were estimated using Kaplan-Meier analysis. RESULTS: Radical nephroureterectomy was performed in 87 patients and parenchymal sparing ureteral resection in 33. Median age at surgery was 73 years in the radical nephroureterectomy group (IQR 64-76) vs 70 years (IQR 59-77) in the parenchymal sparing ureteral resection group (p = 0.5). The radical nephroureterectomy and parenchymal sparing ureteral resection cohorts had several disparate clinicopathological variables including preoperative hydronephrosis (80% vs 45%, p = 0.0006), stage (pT3 or greater 26% vs 9%, p = 0.01) and baseline estimated glomerular filtration rate (51 vs 63 ml/minute/1.73 m(2), p = 0.009). Patients who underwent radical nephroureterectomy experienced a significantly greater decrease in estimated glomerular filtration rate after surgery (median -7 vs 0 ml/minute/1.73 m(2), p <0.001). Median followup was 4.2 years. Of the patients 79 experienced cancer recurrence and 44 died (28 of upper tract urothelial carcinoma). There were no obvious differences in the rates of recurrence, cancer specific death or overall death by procedure type. However, due to the limited number of events we cannot exclude the possibility that there are large differences in oncologic outcomes by procedure type. CONCLUSIONS: Parenchymal sparing ureteral resection is associated with superior postoperative renal function. However, the impact on cancer control cannot be determined conclusively due to the small sample size and putative selection bias.

Combining imaging and ureteroscopy variables in a preoperative multivariable model for prediction of muscle-invasive and non-organ confined disease in patients with upper tract urothelial carcinoma.

OBJECTIVE: To create a preoperative multivariable model to identify patients at risk of muscle-invasive (pT2+) upper tract urothelial carcinoma (UTUC) and/or non-organ confined (pT3+ or N+) UTUC (NOC-UTUC) who potentially could benefit from radical nephroureterectomy (RNU), neoadjuvant chemotherapy and/or an extended lymph node dissection. PATIENTS AND METHODS: We retrospectively analysed data from 324 consecutive patients treated with RNU between 1995 and 2008 at a tertiary cancer centre. Patients with muscle-invasive bladder cancer were excluded, resulting in 274 patients for analysis. Logistic regression models were used to predict pT2+ and NOC-UTUC. Pre-specified predictors included local invasion (i.e. parenchymal, renal sinus fat, or periureteric) on imaging, hydronephrosis on imaging, high-grade tumours on ureteroscopy, and tumour location on ureteroscopy. Predictive accuracy was measured by the area under the curve (AUC). RESULTS: The median follow-up for patients without disease recurrence or death was 4.2 years. Overall, 49% of the patients had pT2+, and 30% had NOC-UTUC at the time of RNU. In the multivariable analysis, only local invasion on imaging and ureteroscopy high grade were significantly associated with pathological stage. AUC to predict pT2+ and NOC-UTUC were 0.71 and 0.70, respectively. CONCLUSIONS: We designed a preoperative prediction model for pT2+ and NOC-UTUC, based on readily available imaging and ureteroscopic grade. Further research is needed to determine whether use of this prediction model to select patients for conservative management vs RNU, neoadjuvant chemotherapy, and/or extended lymphadenectomy will improve patient outcomes.

Selective arterial embolization for pseudoaneurysms and arteriovenous fistula of renal artery branches following partial nephrectomy.

PURPOSE: We describe the presentation, endovascular management and functional outcomes of 15 patients with renal arterial pseudoaneurysm following open and laparoscopic partial nephrectomy. MATERIALS AND METHODS: An institutional review board approved, Health Insurance Portability and Accountability Act compliant retrospective review of a prospectively maintained database revealed that 7 of 1,160 patients who underwent open partial nephrectomy and 8 of 301 treated with laparoscopic partial nephrectomy were diagnosed with a pseudoaneurysm of a renal artery branch between 2003 and 2010. Some cases were associated with arteriovenous fistula. RESULTS: Diagnosis of pseudoaneurysm was made a median of 14 days after surgery. Gross hematuria was the most frequent symptom. Median estimated glomerular filtration rate measurements at the preoperative evaluation, postoperatively, on the day the vascular lesion was diagnosed, after embolization and at the last followup were 62, 55, 55, 56 and 58 ml/minute/1.73 m(2), respectively. Median followup was 7.8 months. All patients underwent angiography and superselective coil embolization of 1 or more pseudoaneurysms with or without arteriovenous fistula. Eleven patients had immediate cessation of symptoms while 4 had persistent gross hematuria after the procedure. Of these 4 patients 2 were treated with bedside care, 1 required repeat embolization with thrombin, which was successful, and the remaining patient had coagulopathy and underwent radical nephrectomy for persistent bleeding. CONCLUSIONS: Pseudoaneurysms and arteriovenous fistulas of the renal artery are rare complications of partial nephrectomy. Presentation is often delayed. Superselective coil embolization is a safe, minimally invasive treatment option that usually solves the clinical problem and preserves renal function.

Solitary, isolated metastatic disease to the kidney: Memorial Sloan-Kettering Cancer Center experience.

OBJECTIVE: • To analyse the clinical characteristics and outcomes of patients who underwent nephrectomy for solitary, isolated metastatic disease to the kidney. PATIENTS AND METHODS: • From July 1989 to July 2009, we identified 13 patients who underwent nephrectomy for solitary metastasis to the kidney. Patients' demographics, intra-operative variables and outcomes are reported. RESULTS: • The median age at nephrectomy was 52 years (range 33-79). Eleven patients (85%) had an incidentally discovered renal mass, whereas two patients (15%) presented with gross haematuria. • Median time from initial surgery at the primary site to development of metastatic disease to the kidney was 63 months (range 9-136). No patient had evidence of disease at other sites at the time of nephrectomy. In seven patients (54%), the kidney was the first site of recurrence. • The most common primary site was the lung in five patients (38%), followed by the colon in two (15%), chest wall in two (15%) and bone, brain, breast and salivary gland in one patient each (8%). • Of the 14 procedures performed, eight (57%) were partial nephrectomy (PN) and six (43%) were radical nephrectomy (RN). • Four patients died after progression from the primary tumour, all within 2 years of nephrectomy. One patient with a primary chondrosarcoma had no evidence of disease at last follow-up and died from other causes 50 months after nephrectomy. The median follow-up for the eight patients who were alive at last follow-up was 30 months after nephrectomy. Four of these patients had no evidence of disease and four patients were alive with metastatic disease. CONCLUSION: • Kidney involvement by metastatic disease can occur as isolated solitary lesions. Some patients will also have the kidney as the first and only site of metastatic involvement. The presence of an isolated renal metastasis should not be considered an end-stage disease, and nephrectomy can be offered for highly selected patients as a therapeutic option.

Gender differences in radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: Women have been associated with adverse outcomes after radical cystectomy for lower tract urothelial carcinoma. We evaluated the prognostic value of gender in an international cohort of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively studied 754 patients treated with RNU for UTUC without neoadjuvant chemotherapy at nine centers located in Asia, Canada, and Europe. Univariable and multivariable Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. Median follow-up was 40 months (interquartile range: 18-75). RESULTS: The majority of patients was of men (516, 68.4%). Women were older than men at the time of RNU (median: 69.2 vs. 66.5 years; P = 0.0003). Women were less likely to have high-grade disease, undergo lymph node dissection, and to receive adjuvant chemotherapy. Gender was not associated with pathologic stage, lymph node metastasis, lymphovascular invasion, concomitant CIS, tumor architecture, or tumor necrosis. On univariable Cox regression analyses, there was no association between gender and cancer recurrence (P = 0.76) or cancer-specific mortality (P = 0.30). On multivariable Cox regression analyses that adjusted for the effects of clinicopathologic features, gender was not associated with disease recurrence (P = 0.47) or cancer-specific survival (P = 0.15). CONCLUSIONS: We found no difference in histopathologic features and outcomes between men and women treated with RNU for UTUC. Nevertheless, epidemiologic and mechanistic molecular studies should be encouraged to design, analyze, and report gender-specific associations to aid in our understanding of gender impact on UTUC incidence, progression, and metastasis.

Pelvimetric dimensions do not impact upon nerve sparing or erectile function recovery in patients undergoing radical retropubic prostatectomy.

INTRODUCTION: The impact of unfavorable pelvic anatomy on the likelihood of having a nerve sparing radical retropubic prostatectomy (RRP) and the potential correlation between pelvic dimensions and recovery of erectile function (EF) after RRP have not been previously evaluated. AIM: To determine the impact of different pelvic bony and soft tissue dimensions as well as apical prostate depth on the likelihood of performing bilateral nerve sparing and on recovery of EF after RP. METHODS: Between November 2001 and June 2007, 644 potent men undergoing RRP had preoperative MRI where pelvimetry was performed with bilateral nerve sparing in 504 men. Outcomes including varying degrees of recovery of EF (level 1: normal; level 2: partial erections routinely sufficient for intercourse; level 3: partial erections occasionally sufficient for intercourse) were assessed. Median follow-up was 44.1 (interquartile range: 29.2, 65.3) months. We evaluated independent predictors of performing a bilateral nerve sparing procedure and of recovery of EF using multivariable Cox proportional hazards methods. MAIN OUTCOME MEASURES: Likelihood of performing bilateral nerve sparing as well as recovery of EF after RRP. RESULTS: Patients with higher clinical stage and biopsy Gleason score are less likely to undergo bilateral nerve sparing. Surgeon is also a factor in the likelihood of having bilateral nerve sparing RRP. On multivariate Cox regression analysis, factors predictive of recovery of EF were age, pretreatment erectile function, surgeon, and modified Charlson score. None of the pelvimetric dimensions were significant predictors of any degree of recovery of EF. However, the study is limited by its retrospective nature and by being based on MRI evaluations useful for cancer staging rather than anatomical evaluation of pelvimetric dimensions. CONCLUSIONS: We did not find unfavorable pelvic anatomy to impact the likelihood of performing a nerve sparing procedure or to be predictive of any degree of recovery of EF after RRP.

Comparison between laparoscopic and open radical nephroureterectomy in a contemporary group of patients: are recurrence and disease-specific survival associated with surgical technique?

BACKGROUND: Open radical nephroureterectomy (ORN) is the current standard of care for upper tract urothelial carcinoma (UTUC), but laparoscopic radical nephroureterectomy (LRN) is emerging as a minimally invasive alternative. Questions remain regarding the oncologic safety of LRN and its relative equivalence to ORN. OBJECTIVE: Our aim was to compare recurrence-free and disease-specific survival between ORN and LRN. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed data from 324 consecutive patients treated with radical nephroureterectomy (RN) between 1995 and 2008 at a major cancer center. Patients with previous invasive bladder cancer or contralateral UTUC were excluded. Descriptive data are provided for 112 patients who underwent ORN from 1995 to 2001 (pre-LRN era). Comparative analyses were restricted to patients who underwent ORN (n=109) or LRN (n=53) from 2002 to 2008. Median follow-up for patients without disease recurrence was 23 mo. INTERVENTION: All patients underwent RN. MEASUREMENTS: Recurrence was categorized as bladder-only recurrence or any recurrence (bladder, contralateral kidney, operative site, regional lymph nodes, or distant metastasis). Recurrence-free probabilities were estimated using Kaplan-Meier methods. A multivariable Cox model was used to evaluate the association between surgical approach and disease recurrence. The probability of disease-specific death was estimated using the cumulative incidence function. RESULTS AND LIMITATIONS: Clinical and pathologic characteristics were similar for all patients. The recurrence-free probabilities were similar between ORN and LRN (2-yr estimates: 38% and 42%, respectively; p=0.9 by log-rank test). On multivariable analysis, the surgical approach was not significantly associated with disease recurrence (hazard ratio [HR]: 0.88 for LRN vs ORN; 95% confidence interval [CI], 0.57-1.38; p=0.6). There was no significant difference in bladder-only recurrence (HR: 0.78 for LRN vs ORN; 95% CI, 0.46-1.34; p=0.4) or disease-specific mortality (p=0.9). This study is limited by its retrospective nature. CONCLUSIONS: Based on the results of this retrospective study, no evidence indicates that oncologic control is compromised for patients treated with LRN in comparison with ORN.

The effect of tumor location on prognosis in patients treated with radical nephroureterectomy at Memorial Sloan-Kettering Cancer Center.

BACKGROUND: The prognostic impact of primary tumor location on outcomes for patients with upper-tract urothelial carcinoma (UTUC) is still contentious. OBJECTIVE: To test the association between tumor location and disease recurrence and cancer-specific survival (CSS) in patients treated with radical nephroureterectomy (RNU) for UTUC. DESIGN, SETTING, AND PARTICIPANTS: Prospectively collected data were retrospectively reviewed from 324 consecutive patients treated with RNU between 1995 and 2008 at a single tertiary referral center. Patients who had previous radical cystectomy, preoperative chemotherapy, previous contralateral UTUC, or metastatic disease at presentation were excluded. This left 253 patients for analysis. Tumor location was categorized as renal pelvis or ureter based on the location of the dominant tumor. Recurrences in the bladder only, in nonbladder sites, and in any site were analyzed. INTERVENTION: All patients were treated with RNU. MEASUREMENTS: Recurrence-free survival and CSS probabilities were estimated using Kaplan-Meier and Cox regression analyses. RESULTS AND LIMITATIONS: Median follow-up for survivors was 48 mo. The 5-yr recurrence-free probability (including bladder recurrence) and CSS estimates were 32% and 78%, respectively. On multivariable analysis, pathologic stage was the only predictor for disease recurrence (p=0.01). Tumor location was not an independent predictor for recurrence (hazard ratio: 1.19; p=0.3), and there was no difference in the probability of disease recurrence between ureteral and renal pelvic tumors (p=0.18). On survival analysis, we also found no differences between ureteral and renal pelvic tumors on probability of CSS (p=0.2). On multivariate analysis, pathologic stage (p<0.0001) and nodal status (p=0.01) were associated with worse CSS. This study is limited by its retrospective nature. CONCLUSIONS: Our study did not show any differences in recurrence and CSS rates between patients with ureteral and renal pelvic tumors treated with RNU.

Recovery of renal function after open and laparoscopic partial nephrectomy.

BACKGROUND: Although oncologic outcomes appear to be similar after laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN), data on renal function are lacking. OBJECTIVE: To evaluate the change over time in renal function after LPN and OPN. DESIGN, SETTING, AND PARTICIPANTS: We identified 987 patients with a single sporadic tumor and a normal contralateral kidney who were treated by LPN (n=182) and OPN (n=805) between January 2002 and July 2009. INTERVENTION: All patients underwent LPN or OPN at Memorial Sloan-Kettering Cancer Center. MEASUREMENTS: Estimated glomerular filtration rate (GFR) was calculated using the abbreviated Modification of Diet in Renal Disease formula. We created a multivariable generalized estimating equations linear model that predicted GFR based on the time from surgery, preoperative GFR, tumor size, American Society of Anesthesiologists score, and ischemia time. RESULTS AND LIMITATIONS: Mean patient age, tumor size, and ASA score were similar between LPN and OPN patients. The baseline preoperative GFR was lower in the laparoscopic group (67 ml/min per 1.73 m(2) vs 73 ml/min per 1.73 m(2); p<0.001). The mean ischemia time was shorter after LPN than OPN (35 min vs 40 min, respectively; p<0.001). In a multivariable model, the interaction term between time from surgery and approach was statistically significant (p=0.045), indicating that there was a differential effect on recovery of renal function over time by approach. Laparoscopically treated patients maintained a slightly higher renal function than those treated via an open approach. The 2-mo and 6-mo predicted GFR for a typical patient increased slightly from 65 ml/min per 1.73 m(2) to 67 ml/min per 1.73 m(2), respectively, for those treated laparoscopically but remained constant at 62 ml/min per 1.73 m(2) after OPN. CONCLUSIONS: Our data suggest that the surgical approach has a small effect on the recovery of renal function after partial nephrectomy. Laparoscopically treated patients maintained slightly higher renal function.