Scott E. Delacroix

The Impact of Targeted Molecular Therapies on the Level of Renal Cell Carcinoma Vena Caval Tumor Thrombus

BACKGROUND Targeted molecular therapies (TMTs) previously have demonstrated oncologic activity in renal cell carcinoma (RCC) by reducing the size of primary tumors and metastases. OBJECTIVE To assess the cytoreductive effect of TMTs on inferior vena cava tumor thrombi. DESIGN, SETTING, AND PARTICIPANTS A multi-institutional database of patients treated with TMTs for RCC was reviewed. The subset with in situ level II or higher caval thrombi (above renal vein) was assessed for radiographic response in thrombus size and level. Pre- and posttreatment characteristics of this population were assessed for predictors of response in height, diameter, and level of the tumor thrombi. MEASUREMENTS The main outcome measured was a change in the clinical level of tumor thrombus following TMT. We also measured radiographic responses in thrombus size and location before and after TMT. RESULTS AND LIMITATIONS Twenty-five patients met the inclusion criteria. Before TMT, thrombus level was II in 18 patients (72%), III in 5 patients (20%), and IV in 2 patients (8%). The first-line therapy was sunitinib in 12 cases; alternative TMTs were administered in 13. The median duration of therapy was two cycles (range: one to six cycles). Following TMT, 7 patients (28%) had a measurable increase in thrombus height, 7 (28%) had no change, and 11 (44%) had a decrease. One patient (4%) had an increase in thrombus-level classification, 21 (84%) had stable thrombi, and in 3 (12%) the thrombus level decreased. There was only one case (4%) where the surgical approach was potentially affected by tumor thrombus regression (level IV to III). No statistically significant predictors of tumor thrombus response to TMTs were found. Limitations include the descriptive and retrospective study design. Because TMTs were initiated according to physician and/or patient preferences, and not all patients were treated in anticipation of surgery, no conclusions could be drawn regarding selection and duration of therapy. Thus it may not be appropriate to extrapolate our experience to all patients with locally advanced RCC. Although this is the largest reported experience with in situ caval tumor thrombi treated with TMT, this series lacks sufficient statistical power to assess the usefulness of TMTs adequately in tumor thrombus cytoreduction. CONCLUSIONS TMT had a minimal clinical effect on RCC tumor thrombi. Only patients treated with sunitinib had clinical thrombus regression; however, the clinical magnitude and relevance of this effect is not clear and should be investigated prospectively.

Safety of Presurgical Targeted Therapy in the Setting of Metastatic Renal Cell Carcinoma

BACKGROUND In patients with metastatic renal cell carcinoma (mRCC), the timing of systemic targeted therapy in relation to cytoreductive nephrectomy (CN) is under investigation. OBJECTIVE To evaluate postoperative complications after the use of presurgical targeted therapy prior to CN. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of all patients who underwent a CN at The University of Texas M.D. Anderson Cancer Center from 2004 to 2010 was performed. Inclusion in this study required documented evidence of mRCC, with treatment incorporating CN. INTERVENTIONS Patients receiving presurgical systemic targeted therapy prior to CN were compared to those undergoing immediate CN. MEASUREMENTS Complications were assessed using the modified Clavien system for a period of 12 mo postoperatively. RESULTS AND LIMITATIONS Presurgical therapy was administered to 70 patients prior to CN (presurgical), while 103 patients had an immediate CN (immediate). A total of 232 complications occurred in 57% of patients (99 of 173). Use of presurgical systemic targeted therapy was predictive of having a complication>90 d postoperatively (p=0.002) and having multiple complications (p=0.013), and it was predictive of having a wound complication (p<0.001). Despite these specific complications, presurgical systemic targeted therapy was not associated with an increased overall complication risk on univariable or multivariate analysis (p=0.064 and p=0.237) and was not predictive for severe (Clavien ≥3) complications (p=0.625). This study is limited by its retrospective nature. As is inherent to any retrospective study reporting on complications, we are limited by reporting bias and the potential for misclassification of specific complications. CONCLUSIONS Despite an increased risk for specific wound-related complications, overall surgical complications and the risk of severe complications (Clavien ≥3) are not greater after presurgical targeted therapy in comparison to upfront cytoreductive surgery.

Can a Durable Disease-Free Survival be Achieved With Surgical Resection in Patients With Pathological Node Positive Renal Cell Carcinoma?

PURPOSE Patients with isolated regional nodal metastases from renal cell carcinoma are a distinct cohort for which resection of involved lymph nodes may be therapeutic. We assessed the outcomes of patients treated at our institution with pathological node positive renal cell carcinoma without concomitant metastatic disease (T(any)N+M0). MATERIALS AND METHODS A total of 2,521 patients with nonmetastatic renal cell carcinoma (T(any)N(any)M0) of any histological subtype treated with nephrectomy were identified between 1995 and 2009. Pathological regional node positive disease in the absence of clinically detectable metastases (T(any)N(1-2)M0) was present in 68 patients (2.7%) and these patients formed our study cohort. Patients were assessed for timing and location of recurrence, disease specific survival and overall survival. Multivariate Cox regression analysis was performed to define factors predictive of recurrence and overall survival. RESULTS Of the 68 patients with T(any)N(1-2)M0 renal cell carcinoma 22.1% were free of disease at a median followup of 43.5 months. In those patients experiencing recurrence, disease was detected within the first 4 months after surgery in 51% and was most commonly detected at multiple organ sites. The Kaplan-Meier estimated 5-year overall survival and disease specific survival was 37% and 39%, respectively. Predictors of a favorable outcome included an Eastern Cooperative Oncology Group performance status of 0, single node involvement, absence of sarcomatoid features and papillary histology. CONCLUSIONS Nephrectomy with lymph node dissection can provide a durable disease-free survival in a proportion of patients with regionally advanced renal cell carcinoma and limited lymph node metastases.

The role of lymphadenectomy in renal cell carcinoma

Purpose of review To critically appraise the current literature on the benefits of lymphadenectomy in patients with renal cell carcinoma. Many questions exist including: What is a ‘standard’ versus ‘extended’ lymph node dissection (LND)? What is the morbidity of a LND? What type of patient may derive the most benefit from LND? On the basis of preoperative staging, what is the benefit (therapeutic versus staging) for an individual patient? How does the performance of a LND impact current and future adjuvant and neoadjuvant studies? Recent findings Results from the EORTC 30881 trial did not show a therapeutic benefit to performing a ‘standard’ LND in patients with renal cell carcinoma, but the population predominantly comprised patients at the lowest risk of harboring lymph node metastasis. There are no prospective randomized trials with sufficient statistical power to analyze the therapeutic or staging effects in high-risk patients. Summary This review provides a synopsis of the available data regarding the therapeutic and staging benefits of lympadenectomy in the setting of renal cell carcinoma and should assist the urologist in educating affected patients as well as providing the urologist with the current evidenced-based data regarding this longstanding unanswered question.

Positive vascular wall margins have minimal impact on cancer outcomes in patients with non-metastatic renal cell carcinoma (RCC) with tumour thrombus

To evaluate the impact of microscopically positive vascular margins on recurrence and cancer‐specific survival (CSS) in patients with renal cell carcinoma (RCC) with venous thrombus

Renal Cell Carcinoma: What the Surgeon and Treating Physician Need to Know

OBJECTIVE The multimodality approach to treating both localized and metastatic renal cell carcinoma has led to a demand for improved imaging evaluation. We review the information needed from the radiologic studies used to determine treatment strategies. CONCLUSION Adequate preoperative radiologic assessment provides the treating physician with information critical in determining the sequence of treatments, role of nephron-sparing surgery, surgical approach, and timing of systemic therapy for metastatic disease.

Therapeutic strategies for advanced penile carcinoma

Purpose of reviewThe article will review the treatment of regionally advanced squamous cell carcinoma (SCC) of the penis and will highlight contemporary therapeutic strategies in advanced penile carcinoma. Recent findingsAdvanced penile cancer as defined by bulky inguinal or pelvic metastasis is treated in a systematic fashion by integrating systemic and local therapies. Contemporary series show the morbidity from consolidative surgery has been reduced, whereas the integration of neoadjuvant and adjuvant therapies may provide improved cancer-specific outcomes over single modality treatment. Multiple clinical and pathologic features guide the treatment of advanced disease and aid in determining the appropriate use of neoadjuvant or adjuvant therapies. SummaryThe current treatment of advanced SCC of the penis has evolved to include multimodal treatments for patients with advanced locoregional disease.

The role of lymph node dissection in renal cell carcinoma

Due to the relatively heterogeneous metastatic spread of renal cell carcinoma (RCC) through both hematogenous and lymphatogenous routes, the surgical extirpation of regional lymph nodes in the treatment of RCC has long been a controversial topic. Individual risk is dependent on multiple variables including tumor stage, grade, and histologic sub-type, in addition to many others. Controversy exists over whether lymph node dissection (LND) simply provides improved staging or whether removal of pathologic nodes offers a therapeutic advantage. Herein, we evaluate the available data regarding the use of LND in the treatment of RCC. While we believe that LND may provide an opportunity for cure in a select group of patients, there are many variables to consider when determining its applicability to an individual patient.

The Role of Lymph Node Dissection in Renal Cell Carcinoma

The role of lymph node dissection (LND) in the staging and treatment of renal cell carcinoma has long been a topic of debate. The controversy has focused on whether LND is purely an adjunctive staging procedure or has a therapeutic role in the management of this disease. Potential benefits include enhanced staging, better selection for adjuvant therapies/clinical trials, a decrease in recurrence rates, and improved disease-specific and overall survival. This article reviews the available literature on LND in renal cell carcinoma and discusses the potential benefits of aggressive surgical resection in select high-risk patients.

Nodal disease in the setting of metastatic renal cell carcionoma: Can a lymph node dissection alter outcomes?

386 Background: The impact of lymph node dissection (LND) in patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy (CN) is unclear. The aims of this study were to determine the predictive ability of LN status for overall survival (OS) in patients treated with CN in the targeted therapy era and if LND increases the morbidity of CN. METHODS We performed a retrospective review of all patients with mRCC treated with CN at a single institution between 2004-2010. Patients participating in open or unpublished trials were excluded, leaving 173 patients for analysis. LNs >1cm by long axis diameter were considered clinically positive (cN+). OS was calculated using COX proportional hazard regression. Complications were classified using the modified Clavien system. RESULTS Sixty-five (37.6%) patients were clinically node positive (cN+). Median OS was significantly worse for the cN+ patients compared to cN0 patients [17.5 vs 29.1 mos;HR 1.8;(1.3-2.6)]. Clinical node status remained an independent predictor of OS on multivarible analysis (MV) [HR 1.7;CI 1.1-2.7]. LND was performed in 61/65 (93.4%) cN+ patients and in 56/108 (52%) of cN0 patients. Pathologic node positive disease (pN+) was more common in cN+ compared to cN0 patients (75% vs. 23%,p <0.001). pN+ patients had worse median OS than pN0 patients [16.0 v 35.5 mos;HR 2.3(1.5-3.6)]. Among pN+ patients (n=54), complete resection of all identifiable nodal disease was associated with an improved OS compared to patients with unresectable nodal disease (n=4) [16.0 v 5.6 mos;HR 2.9(1.0-8.3)]. On univariate analysis LND patients were more likely to have a post-operative complication (64% vs 43%,p=0.008) and more specifically chylous ascites (12 v 0,p=0.01). Despite this association, LND did not reach statistical significance when MV analysis was performed [OR 1.9;(0.9-3.8)]. CONCLUSIONS Among patients undergoing CN, those with cN+ disease had worse OS. Likewise, pN+ patients have worse OS than pN0 patients. LND is associated with higher morbidity than CN alone. Further efforts are needed to determine removal of pathologic nodes alters the natural history of the disease, and if the benefit offsets the increased morbidity.