Patrick Espiritu

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.

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

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.

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.

Predicting ease of perinephric fat dissection at time of open partial nephrectomy using preoperative fat density characteristics

To predict the ease of perinephric fat surgical dissection at the time of open partial nephrectomy (OPN) using perinepheric fat density characteristics as measured on preoperative computed tomography (CT).

The merits of cytology in the workup for upper tract urothelial carcinoma - a contemporary review of a perplexing issue

INTRODUCTION The importance of upper tract cytology for evaluating tumors is unclear. We correlated upper tract cytology with histologic findings in patients who underwent nephroureterectomy for upper tract urothelial carcinoma (UTUC) at a single tertiary care referral center. MATERIALS AND METHODS 137 patients underwent nephroureterectomy between 2004 and 2012. 18 patients were excluded (benign tumors, atrophic kidneys with the remaining 119 patients serving as our study population). Upper tract cytology from the renal pelvis and/or ureter were retrospectively reviewed and analyzed with final pathology data in the remaining patients with UTUC. RESULTS 57% (68/119) had preoperative upper tract cytology collected. 73% (50/68) patients had abnormal cytology (positive, suspicious) with a sensitivity of 74% (which increased to 90% if atypical included), specificity of 50% and a positive predictive value of 98%. High grade tumors were more common than expected (77% high grade vs. 20% low grade). Abnormal cytology did not predict T stage or tumor grade. Interestingly, positive upper tract cytology was found in all of the UTUC CIS specimen. CONCLUSIONS Upper tract cytology has been utilized to support the diagnosis of upper tract urothelial carcinoma. Our data demonstrates that abnormal cytology correlates well with the presence of disease but does not predict staging or grading in these respective patients.

Caval tumor thrombus volume influences outcomes in renal cell carcinoma with venous extension

INTRODUCTION Surgery for renal cell carcinoma with tumor thrombus has a high potential morbidity rate, and the current classification system based on proximal tumor thrombus level (TTL) has not been shown to consistently predict outcomes. AIM To assess the prognostic value of inferior vena cava tumor thrombus volume (IVC-TV) for determining the perioperative complications as well as with survival end points. METHODS From June 2001 to June 2012, we identified 147 patients who underwent radical nephrectomy with venous thrombi. In total, 66 patients had IVC involvement and available imaging for review. IVC-TV was measured by cross-sectional area and height measurement for each axial slice. Linear, logistic models and Cox proportional hazard was used for analysis. RESULTS Median IVC-TV was 16.5 cm(3), and 18 patients had TTL≥III. In total, 57 Clavien I-V complications were documented in 32 patients including 3 deaths. On multivariate analysis, age>65 years, American Society of Anesthesiologists>3, and IVC-TV>15 cm(3) were independent predictors for perioperative complications. Disease progression (PoD) occurred in 78% of patients, and metastatic disease (hazard ratio [HR] = 3.33, P<0.01) and non-clear cell histology (HR = 2.98, P = 0.02) were independent predictors of PoD. Median time to death was 16 months (interquartile range: 5.2-42.9). On Cox regression analysis, metastatic disease, non-clear cell histology, IVC-TV>15 cm(3), and TTL III/IV were significantly associated with overall survival. As a preoperative variable, IVC-TV>15 cm(3) was shown to be an independent predictor of PoD (HR = 2.3, P = 0.01) and overall survival (HR = 2.21, P = 0.03). CONCLUSION IVC-TV has value as a prognostic indicator, which is superior to TTL in the setting of renal cell carcinoma with IVC venous thrombus.

Effect of utilization of veno-venous bypass vs. cardiopulmonary bypass on complications for high level inferior vena cava tumor thrombectomy and concomitant radical nephrectomy

ABSTRACT Purpose: To determine if patients with renal cell carcinoma (RCC) with levels III and IV tumor thrombi are receive any reduction in complication rate utilizing veno-venous bypass (VVB) over cardiopulmonary bypass (CPB) for high level (III/IV) inferior vena cava (IVC) tumor thrombectomy and concomitant radical nephrectomy. Materials and Methods: From May 1990 to August 2011, we reviewed 21 patients that had been treated for RCC with radical nephrectomy and concomitant IVC thrombectomy employing either CPB (n =16) or VVB (n=5). We retrospectively reviewed our study population for complication rates and perioperative characteristics. Results: Our results are reported using the validated Dindo-Clavien Classification system comparing the VVB and CPB cohorts. No significant difference was noted in minor complication rate (60.0% versus 68.7%, P=1.0), major complication rate (40.0% versus 31.3%, P=1.0), or overall complication rate (60.0% versus 62.5%, P=1.0) comparing VVB versus CPB. We also demonstrated a trend towards decreased time on bypass (P=0.09) in the VVB cohort. Conclusion: The use of VVB over CPB provides no decrease in minor, major, or overall complication rate. The use of VVB however, can be employed on an individualized basis with final decision on vascular bypass selection left to the discretion of the surgeon based on specifics of the individual case.

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.

Surgical Management of a Locally Advanced Symptomatic Recurrence of Penile Sarcoma Secondary to Prostate Brachytherapy

UNLABELLED The surgical management of patients with symptomatic metastatic or locally advanced recurrences involving the penis remains poorly characterized. The aim of the present abstract and video is to detail our experience in the surgical management of a specific patient with a locally advanced symptomatic recurrence of penile sarcoma secondary to prostate cancer treated with primary brachytherapy. MATERIALS AND METHODS A 70 year old male patient initially treated for localized prostate cancer with interstitial brachytherapy at an outside facility developed an unfortunate secondary malignancy consisting of a locally advanced penile sarcoma involving as well the prostate and base of the bladder. Despite our best efforts to control his pain, he developed a very symptomatic local recurrence with a secondary penile abscess and purulent periurethral drainage. At this time, it was felt a surgical resection consisting of a total penectomy, urethrectomy, cystoprostatectomy, and ileal conduit urinary diversion would be the best option for local cancer control in this particular patient. RESULTS The patient underwent the surgical resection without any complications as illustrated in this surgical video, with a jejunal intestinal mass identified at the time of surgery which was resected with a primary bowel anastomosis performed. The patient was discharged from hospital uneventfully with his symptomatic local recurrence being successfully managed and the patient no longer requiring oral narcotics for pain control. The pathological report confirmed a locally advanced sarcoma involving the penile, prostate, and bladder which was resected with negative surgical margins and the jejunal mass was confirmed to represent a small bowel sarcoma metastatic site. CONCLUSION As highlighted in the present video, the treatment of a symptomatic sarcoma local recurrence contiguously involving the penis can be successfully managed provided the patient is informed of the potential morbidity and psychosocial implications imparted by performing a total penectomy and adjacent organ resection.