Patterns of Lymphatic Metastases in Upper Tract Urothelial Carcinoma and Proposed Dissection Templates.

PURPOSE: Information on patterns of lymph node metastases for upper tract urothelial carcinoma is sparse. We investigated patterns of lymph node metastases in upper tract urothelial carcinoma. MATERIALS AND METHODS: We performed a retrospective multi-institutional study of 73 patients with N+M0 upper tract urothelial carcinoma who underwent template lymphadenectomy during nephroureterectomy. Anatomical locations of tumor, and number of lymph nodes removed and positive lymph nodes were analyzed and descriptive statistics were performed. RESULTS: On the right side the 20 renal pelvis tumors had lymph node metastases to the hilum in 22.1% of cases, and to paracaval, retrocaval and interaortocaval regions in 44.1%, 10.3% and 20.6%, respectively. The 10 proximal ureter tumors had lymph node metastases to the hilum in 46.2% of cases, and to paracaval and retrocaval regions in 46.2% and 7.7%, respectively. The 2 distal ureter tumors had lymph node metastases equally to the paracaval and pelvic regions. On the left side the 24 renal pelvis tumors had lymph node metastases to the hilum region in 50.0% of cases and to the para-aortic region in 30.0%. The 8 proximal ureter tumors had lymph node metastases to the hilum region in 36.4% of cases and the para-aortic region in 63.6%. The 5 mid ureter tumors had lymph node metastases to the para-aortic, common iliac and internal iliac regions in 40%, 40% and 20% of cases, respectively. The 4 distal ureter tumors had lymph node metastases to the para-aortic, common iliac, external iliac and internal iliac regions in 33.3%, 33.3%, 16.7% and 16.7% of cases, respectively. Interaortocaval involvement from both sides as well as out of field lymph node metastases appeared to occur secondarily. Consolidated templates were constructed based on the available data. CONCLUSIONS: Upper tract urothelial carcinoma has characteristic patterns of lymph node metastases depending on the side and anatomical location of the primary tumor, including right-to-left migration and involvement of interaortocaval nodes in the setting of proximal disease. Standardized dissection templates should be prospectively evaluated in multicenter trials to assess morbidity and potential clinical benefit.

Predicting postoperative complications of inguinal lymph node dissection for penile cancer in an international multicentre cohort.

OBJECTIVES: To assess the potential complications associated with inguinal lymph node dissection (ILND) across international tertiary care referral centres, and to determine the prognostic factors that best predict the development of these complications. MATERIALS AND METHODS: A retrospective chart review was conducted across four international cancer centres. The study population of 327 patients underwent diagnostic/therapeutic ILND. The endpoint was the overall incidence of complications and their respective severity (major/minor). The Clavien-Dindo classification system was used to standardize the reporting of complications. RESULTS: A total of 181 patients (55.4%) had a postoperative complication, with minor complications in 119 cases (65.7%) and major in 62 (34.3%). The total number of lymph nodes removed was an independent predictor of experiencing any complication, while the median number of lymph nodes removed was an independent predictor of major complications. The American Joint Committee on Cancer stage was an independent predictor of all wound infections, while the patient's age, ILND with Sartorius flap transposition, and surgery performed before the year 2008 were independent predictors of major wound infections. CONCLUSIONS: This is the largest report of complication rates after ILND for squamous cell carcinoma of the penis and it shows that the majority of complications associated with ILND are minor and resolve without prolonged morbidity. Variables pertaining to the extent of disease burden have been found to be prognostic of increased postoperative morbidity.

Patient and disease-specific factors and their influence on urinary reconstruction choice at a referral center.

PURPOSE: To evaluate potential socioeconomic and demographic factors that may influence or be associated with various types of urinary reconstruction (UR) following a radical cystectomy (RC) accounting for existing clinical variables. METHODS: There were 828 patients that underwent a RC and UR between 2000 and 2013. After excluding patients that did not meet medical or surgical criteria for a continent urinary reconstruction (CUR-orthotopic neobladder or continent catheterizable pouch), there were 714 patients available for analysis. Socioeconomic and demographic data along with disease-specific variables were recorded preoperatively and analyzed to determine a correlation with a particular type of UR. RESULTS: Non-continent urinary reconstruction (ileal conduit or cutaneous ureterostomies) and CUR accounted for 78.3 % (559/714) and 21.7 % (155/714) of UR following RC, respectively. On univariate analysis, younger age, marital status, employment status, type of insurance, ASA score, and preoperative glomerular filtration rate were significantly associated with CUR (p < 0.01). Travel distance, race, and education level were not factors for UR type. Additionally, there was no significant difference between males and females receiving a CUR. On multivariate analysis, older age [odds ratio (OR) 0.85, p < 0.01], marital status (OR 0.28, p < 0.01), insurance status (OR 0.22, p = 0.04), and higher ASA score (OR 0.50, p < 0.01) remained independent predictors of those less likely to receive a CUR. CONCLUSION: Predictable socioeconomic and demographic influences exist between the choice of UR after RC. Increasing age corresponds to a decreasing likelihood of receiving a CUR. No significant difference was seen between men and women in undergoing a CUR.

Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer.

BACKGROUND: The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. OBJECTIVE: We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS: Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. INTERVENTION: NAC and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. RESULTS AND LIMITATIONS: Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6). CONCLUSIONS: Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. PATIENT SUMMARY: There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.

Salvage surgical resection for isolated locally recurrent inguinal lymph node metastasis of penile cancer: international study collaboration.

PURPOSE: We assessed the merit of performing salvage inguinal lymph node dissection in those infrequent cases of penile cancer with locally recurrent inguinal lymph node metastases in the absence of other suspected sites of disease. MATERIALS AND METHODS: A total of 20 patients were retrospectively identified as having undergone salvage inguinal lymph node dissection for locally recurrent penile cancer. Patients were previously treated with primary inguinal lymph node dissection with curative intent. At the time of salvage inguinal lymph node dissection, superficial and deep inguinal lymph node dissection was performed with resection outside of the standardized surgical template if there was inguinal recurrence outside of this region. RESULTS: All cases were primary penile squamous cell carcinomas. Median time to recurrence from initial inguinal lymph node dissection was 7.7 months (range 3.1 to 35.0). At salvage inguinal lymph node dissection a median of 3 lymph nodes (range 1 to 17) was resected with a median of 2 (range 1 to 7) nodes positive for malignancy. Median overall survival after salvage inguinal lymph node dissection was 10.1 months (95% CI 1.9-18.3) and median disease specific survival after salvage inguinal lymph node dissection was 16.4 months (95% CI 5.1-27.8). Of the initial 20 patients 9 have no evidence of disease (median followup 12.0 months, range 7.1 to 70.1). Postoperative complications developed in 11 patients, including wound infections in 6, postoperative severe (debilitating) lymphedema in 4 and seroma in 1. CONCLUSIONS: Salvage inguinal lymph node dissection is a potentially curative treatment in patients with penile cancer with locally recurrent inguinal lymph node metastases in the absence of occult disease. Patients undergoing such salvage surgery should be informed of the high likelihood of postoperative complications.

Surgical outcomes in the management of isolated nodal recurrences: a multicenter, international retrospective cohort.

PURPOSE: We report a multicenter international cohort representing what is to our knowledge the largest surgical experience with managing isolated retroperitoneal nodal recurrence of renal cell carcinoma, a unique subset of locoregional disease, yet to be described in detail. MATERIALS AND METHODS: Patients with isolated nodal recurrence of pTanyN+M0 disease after nephrectomy were identified by retrospective chart review at 3 independent institutions. Progression-free survival was estimated by the Kaplan-Meier method and used to compare survival outcomes between primary T(1-2)N(any)M0 and T3N(any)M0 tumors as well as clear cell and nonclear cell histology renal cell carcinoma. RESULTS: A total of 22 patients met study inclusion criteria. Median time to local postoperative recurrence was 31.5 months (IQR 12.9-43.3). After resection of isolated nodal recurrence 10 patients (46%) had a secondary recurrence at a median of 11.2 months (IQR 8.1-18.4), of whom 2 (9%) died of the disease. Overall median progression-free survival was 12.7 months, including 24.8 months for T(1-2)N(any)M0 tumors, 9.9 months for T3N(any)M0 tumors, and 13.4 and 17.6 months for clear and nonclear cell renal cell carcinoma, respectively. CONCLUSIONS: Surgical resection represents the best curative option for patients who present with isolated retroperitoneal lymph node recurrence of renal cell carcinoma. Durable postoperative progression-free survival is attainable in many patients regardless of histology or clinical TNM stage. In addition, our cohort showed a lower renal cell carcinoma related mortality rate than in previous series of local metastasis. As such, all patients free of precluding comorbidities should be considered candidates for complete surgical resection performed by an experienced genitourinary surgeon.

Effect of tumor size on recurrence-free survival of upper tract urothelial carcinoma following surgical resection.

OBJECTIVE: To identify predictors of recurrence-free survival (RFS) based on the clinicopathological features of patients with upper tract urothelial carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU) with bladder cuff resection. MATERIALS AND METHODS: We retrospectively reviewed the records of patients from October 1998 to July 2012 at our tertiary institution and identified 120 patients with sufficient data who underwent RNU for UTUC. We recorded various clinical and histopathological parameters as potential predictors of outcome. Recurrence was defined as any occurrence of urothelial carcinoma after RNU either intravesically, local/regionally, or at distant sites. Univariate, multivariate, and RFS analyses were conducted using the Cox regression and Kaplan-Meier methods. RESULTS: The median age of our cohort was 71 years (interquartile range: 64-78). Median RNU-specimen tumor size was 3.0 cm (interquartile range: 2.0-5.0 cm). Fifty-four patients (45%) had a tumor<3.0 cm and 66 (55%) had a tumor≥3.0 cm. Eighty patients (66.7%) had organ-confined UTUC (≤pT2) and 40 (33.3%) had non-organ-confined UTUC (≥pT3). Sixty-five patients (54.2%) experienced at least 1 recurrence. Forty-three patients (35.8%) had at least 1 episode of intravesical recurrence and 28 (23.3%) had distant recurrence. A multivariate analysis revealed non-organ-confined disease (hazard ratio [HR] = 3.62, P<0.001), tumor diameter≥3 cm (HR = 1.97, P = 0.011), and male gender (HR = 1.81, P = 0.047) to be significant independent predictors of disease recurrence. The 5-year RFS rate was 46.9% and 25.8% for patients with tumor size<3 and ≥3 cm, respectively. CONCLUSIONS: Following RNU, the incidence of recurrence remains high among patients with UTUC. In our cohort of patients, tumor diameter≥3.0 cm, non-organ-confined UTUC, and male gender constitute important risk factors for poor RFS outcomes following RNU. These patients require diligent postoperative surveillance and may potentially benefit from perioperative systemic therapy.

New therapeutic targets in the management of urothelial carcinoma of the bladder.

Urothelial carcinoma of the bladder, despite the myriad of treatment approaches and our progressively increasing knowledge into its disease processes, remains one of the most clinically challenging problems in modern urological clinical practice. New therapies target biomolecular pathways and cellular mediators responsible for regulating cell growth and metabolism, both of which are frequently overexpressed in malignant urothelial cells, with the intent of inducing cell death by limiting cellular metabolism and growth, creating an immune response, or selectively delivering or activating a cytotoxic agent. These new and novel therapies may offer a potential for reduced toxicity and an encouraging hope for better treatment outcomes, particularly for a disease often refractory or not amenable to the current therapeutic approaches.