Complete Histologic Remission after Sunitinib Neoadjuvant Therapy in T3b Renal Cell Carcinoma

The authors present the first case report of complete histologic remission after neoadjuvant sunitinib treatment on primary renal tumour and vena cava thrombus. A 78-yr-old woman with an Eastern Cooperative Oncology Group (ECOG) score of 0 presented with a T3b renal tumour. She refused surgical treatment but agreed to percutaneous biopsy and medical treatment. A Fuhrman III renal cell carcinoma was histologically confirmed on percutaneous biopsy, and sunitinib treatment was administered over 6 mo. A significant objective response was observed for tumour size and thrombus. The patient finally accepted surgical treatment. Pathologic examination concluded with a complete response of primary tumour and thrombus.     

Predicting Occult Multifocality of Renal Cell Carcinoma

Background

Multifocal renal cell carcinoma (RCC) has been reported in up to 25% of all radical nephrectomy specimens. Modern imaging tends to underestimate the rate of multifocality. Recognition of multifocality before treatment may guide physicians and patients to the type of intervention and tailor long-term follow-up.

Objective

Our aim was to develop and assess preoperative nomograms to predict occult multifocal RCC.

Design, setting, and participants

We evaluated 560 consecutive patients undergoing radical nephrectomy for clinically localized suspected sporadic RCC between 2000 and 2008 in a tertiary center. Clinically manifest multifocal lesions were excluded. Logistic regression models were used to assess the potential risk factors of occult multifocality with and without pathologic variables that may be available with preoperative biopsy. Nomograms were developed and assessed for diagnostic properties.

Interventions

All patients underwent radical nephrectomy.

Measurements

Assessments of risk factors for occult multifocal RCC were obtained using regression models and nomograms.

Results and limitations

The incidence of occult multifocality was 7.9%. Significantly associated predictors of multifocality were male gender, family history of malignancy other than RCC, radiographic size of the lesion, histologic subtype other than clear cell, and Fuhrman grade IV. The two designed nomograms had 0.75 and 0.82 concordance indices, respectively.

Conclusions

Our data suggest that occult multifocal RCC is more frequently associated with small (2–4 cm) renal lesions. Male gender, family history of kidney cancer, histologic subtype, and grade are strongly associated with an increased risk of occult multifocal RCC. The developed nomograms had good predictive accuracy that was enhanced when combined with pathologic variables.     

ClearCode34: A Prognostic Risk Predictor for Localized Clear Cell Renal Cell Carcinoma

Background

Gene expression signatures have proven to be useful tools in many cancers to identify distinct subtypes of disease based on molecular features that drive pathogenesis, and to aid in predicting clinical outcomes. However, there are no current signatures for kidney cancer that are applicable in a clinical setting.

Objective

To generate a signature biomarker for the clear cell renal cell carcinoma (ccRCC) good risk (ccA) and poor risk (ccB) subtype classification that could be readily applied to clinical samples to develop an integrated model for biologically defined risk stratification.

Design, setting, and participants

A set of 72 ccRCC sample standards was used to develop a 34-gene classifier (ClearCode34) for assigning ccRCC tumors to subtypes. The classifier was applied to RNA-sequencing data from 380 nonmetastatic ccRCC samples from the Cancer Genome Atlas (TCGA), and to 157 formalin-fixed clinical samples collected at the University of North Carolina.

Outcome measurements and statistical analysis

Kaplan-Meier analyses were performed on the individual cohorts to calculate recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Training and test sets were randomly selected from the combined cohorts to assemble a risk prediction model for disease recurrence.

Results and limitations

The subtypes were significantly associated with RFS (p < 0.01), CSS (p < 0.01), and OS (p < 0.01). Hazard ratios for subtype classification were similar to those of stage and grade in association with recurrence risk, and remained significant in multivariate analyses. An integrated molecular/clinical model for RFS to assign patients to risk groups was able to accurately predict CSS above established, clinical risk-prediction algorithms.

Conclusions

The ClearCode34-based model provides prognostic stratification that improves upon established algorithms to assess risk for recurrence and death for nonmetastatic ccRCC patients.

Patient summary

We developed a 34-gene subtype predictor to classify clear cell renal cell carcinoma tumors according to ccA or ccB subtypes and built a subtype-inclusive model to analyze patient survival outcomes.     

Successful Sorafenib Treatment for Metastatic Renal Cell Carcinoma in a Case with Chronic Renal Failure

Treatment options for patients with end-stage renal disease (ESRD) and metastatic renal cell carcinoma (mRCC) are limited. We report the case of a 69-yr-old male who was treated with sorafenib after failure of immunotherapy. The treatment has resulted in remission with stable disease for 13 mo so far. Sorafenib seems to be a safe treatment option for patients with ESRD and mRCC, but further studies are required.     

Survival and Impact of Clinical Prognostic Factors in Surgically Treated Metastatic Renal Cell Carcinoma

Background

The survival impact of metastasectomy for metastatic renal cell carcinoma (mRCC) is still an active research field, particularly in the multimodal/targeted therapy era.

Objective

To determine the survival impact of clinical prognostic factors and their application to stratification of patients according to their prognosis so clinicians may be aided in their management of mRCC.

Design, setting, and participants

Retrospective, bi-institutional cohort study of 109 consecutive patients (71 male and 38 female; median age: 62 yr (range: 25–82 yr) with renal cell carcinoma (RCC) who underwent partial or radical nephrectomy and at least one metastasectomy for mRCC.

Intervention

Metastasis resection from various anatomic sites with the aim of completely removing detected lesions.

Outcome measurements and statistical analysis

Univariable and multivariable Cox regression models were used to analyse the impact of clinical prognostic factors on cancer-specific survival (CSS). Kaplan-Meier analysis with the log-rank test was used to compare CSS. Receiver operating characteristic (ROC) analysis was performed to test accuracy of prognostic groups. The α error for statistical significance was set at 0.05.

Results and limitations

Multivariable analysis revealed that primary tumour T stage ≥3 (hazard ratio [HR]: 2.8; p < 0.01), primary tumour Fuhrman grade ≥3 (HR: 2.3; p < 0.03), nonpulmonary metastases (HR: 3.1; p < 0.03), disease-free interval ≤12 mo (HR: 2.3; p < 0.058), and multiorgan metastases (HR: 2.5; p < 0.04) were independent pretreatment prognostic factors. Leuven-Udine (LU) prognostic groups based on these covariates were created and analysed with Kaplan-Meier and log-rank tests. The 2- and 5-yr CSS were significantly different; the respective group A CSS rates were 95.8% and 83.1%; group B, 89.9% and 56.4%; group C, 65.6% and 32.6%; and group D, 24.7% and 0% (p < 0.0001). ROC analysis on the accuracy of prognostic grouping revealed respective areas under the curve of 0.87 and 0.88 at 2 and 5 yr. Main limitations to present study are the retrospective design and the presence of different metastasis sites.

Conclusions

LU prognostic groups could be considered an accurate clinical tool to stratify patients according to prognosis and aid clinicians in the management of mRCC.     

A Proposal for Reclassification of the Fuhrman Grading System in Patients with Clear Cell Renal Cell Carcinoma

Background

The conventional Fuhrman grading system, which categorizes renal cell carcinoma (RCC) with grades I, II, III, and IV, is the most widely used predictor assessment of RCC cancer-specific mortality (CSM).

Objectives

The aim of this study was to test the prognostic ability of simplified Fuhrman grading schemes (FGSs) that rely on two- or three-tiered classifications.

Design, setting, and participants

The current study addressed a population of 14 064 patients with clear cell RCC who were treated with partial or radical nephrectomy between 1988–2004, within nine Surveillance, Epidemiology, and End Results (SEER) cancer registries.

Measurements

Univariable and multivariable analyses as well as prognostic accuracy analyses were performed for various FGSs to test their ability to predict CSM rates. The conventional four-tiered FGS was compared to a modified two-tiered FGS in which grades I and II and grades III and IV were combined. A second simplified three-tiered FGS in which grades I and II were combined but grades III and IV were kept separate was also tested.

Results and limitations

The overall 5-yr CSM-free rate was 81.5%. All three FGSs achieved independent predictor status in multivariable analyses. Prognostic accuracy of multivariable models that relied on various FGSs was 83.6% for the modified two-tiered FGS and 83.8% for both the conventional four-tiered and the modified three-tiered FGS.

Conclusions

Our findings indicate that the simplified FGSs perform equally as well as the conventional four-tiered FGS. The use of simplified grading schemes may represent an advantage for pathologists as well as for clinicians caring for patients with RCC.     

Survival Outcome and Treatment Response of Patients with Late Relapse from Renal Cell Carcinoma in the Era of Targeted Therapy

Background

A subset of primarily localized renal cell carcinoma (RCC) patients will experience disease recurrence ≥5 yr after initial nephrectomy.

Objective

To characterize the clinical outcome of patients with late recurrence beyond 5 yr.

Design, setting, and participants

Patients with metastatic RCC (mRCC) treated with targeted therapy were retrospectively characterized according to time to relapse. Relapse was defined as the diagnosis of recurrent metastatic disease >3 mo after initial curative-intent nephrectomy. Patients with synchronous metastatic disease at presentation were excluded. Patients were classified as early relapsers (ERs) if they recurred within 5 yr; late relapsers (LRs) recurred after 5 yr.

Outcome measurements and statistical analysis

Demographics were compared with the Student t test, the chi-square test, or the Fisher exact test. The survival time was estimated with the Kaplan-Meier method, and associations with survival outcome were assessed with univariable and multivariable Cox regression analyses.

Results and limitations

Among 1210 mRCC patients treated with targeted therapy after surgery for localized disease, 897 (74%) relapsed within the first 5 yr and 313 (26%) (range: 5–35 yr) after 5 yr. LRs presented with younger age (p < 0.0001), fewer with sarcomatoid features (p < 0.0001), more clear cell histology (p = 0.001), and lower Fuhrman grade (p < 0.0001). Overall objective response rates to targeted therapy were better in LRs versus ERs (31.8% vs 26.5%; p = 0.004). LRs had significantly longer progression-free survival (10.7 mo vs 8.5 mo; p = 0.005) and overall survival (OS; 34.0 mo vs 27.4 mo; p = 0.004). The study is limited by its retrospective design, noncentralized imaging and pathology review, missing information on metastatectomy, and nonstandardized follow-up protocols.

Conclusions

A quarter of patients who eventually developed metastatic disease and were treated with targeted therapy relapsed over 5 yr from initial nephrectomy. LRs have more favorable prognostic features and consequently better treatment response and OS.     

Assessing the Impact of Ischaemia Time During Partial Nephrectomy

Context

The impact of applying renal ischaemia during nephron-sparing surgery to avoid renal damage in the treated kidney has gained importance in different surgical techniques.

Objective

The main objective of the present study is to point out the limit of renal ischaemia times for warm and cold ischaemia approaches. Important results of research on renal ischaemia and different surgical techniques as well as results of clinical studies concerning renal function after renal ischaemia in partial nephrectomy are highlighted.

Evidence acquisition

A Medline literature research was performed, combining queries on the keywords nephron-sparing surgery, partial nephrectomy, and ischemia. Links to related articles and cross-reading of citations in related articles were surveyed, as were reviews, letters to editors, and information collected from urologic textbooks. The references formed the basis of this review article, with selection and deletion based on the relevance and importance of the content. In a final step, interactive peer review by the expert panel of coauthors completed the review.

Evidence synthesis

Renal ischaemia research showed an increasing renal damage proportional to ischemic time. Current clinical data support safe ischaemia times, within 20 min of warm ischaemia and up to 2 h of cold ischaemia, to minimise renal ischemic damage. To date, no ischaemia dose-response curve or algorithm is available to predict the risk of acute kidney injury and chronic kidney disease in patients undergoing intraoperative ischaemia. In general, there seems to be a higher risk for comorbidity caused by renal damage in patients suffering from kidney tumour.

Conclusions

If ischaemia is required, the tumour should be removed within 20 min of warm ischaemia, regardless of surgical approach. Efforts should be made to start immediately with cold ischaemia, if the feasibility within this span of time seems to be jeopardised. Thus, cold ischaemia times up to 2 h can be tolerated by the kidney, depending on the individual method. Nevertheless, cold ischaemia with ice slush should be kept as short as possible—at best within 35 min. In ischemic nephron-sparing surgery, one of the surgeon's main aims should be to avoid loss of renal function. Only after optimal preoperative appraisal and planning can the best postoperative outcomes for renal function be achieved.     

Prognostic and Therapeutic Impact of the Histopathologic Definition of Parenchymal Epithelial Renal Tumors

Context

In the last few years, the treatment of renal cell carcinoma (RCC) has progressed significantly, and some histopathologic issues have become important for selection and follow-up after medical and surgical therapies.

Objective

The aim of this collaborative article is to review the most recent literature on the role of traditional histopathologic features obtained from renal core biopsy or nephrectomy specimens in the management of confined, locally advanced, and metastatic RCC.

Evidence acquisition

A nonsystematic review of the literature was performed in April 2010 using the Medline database. Multiple free-text searches were performed for the following items: renal cell carcinoma, clear cell, papillary, chromophobe, histologic* subtype*, histotype*, nuclear grade*, necrosis, sarcomatoid differentiation, biopsy, molecular marker*, and cytogenetic marker*. A total of 2369 records were retrieved from Medline, and 263 full-text studies were considered and partially included in the present review. A panel of experts reached consensus on the main subheadings of this paper.

Evidence synthesis

Core needle biopsies can provide important information that is useful to avoid the overtreatment of benign tumors and to help plan watchful waiting or minimally invasive treatments in selected patients. Tumor histotype is fundamental in the pathologic report. In the context of integrated prognostic systems, the combination of the most important clinical and pathologic factors (TNM stage, Fuhrman nuclear grade, presence of necrosis, microvascular invasion, and sarcomatoid dedifferentiation) allows us to reach a high prognostic accuracy. These models can be used to select patients suitable for adjuvant protocols, to design an appropriate follow-up schedule, and to provide careful patient counseling. Molecular and cytogenetic markers should be further evaluated.

Conclusions

The histopathologic definition of parenchymal epithelial renal tumors is fundamental to plan the management and follow-up of patients with locally confined, locally advanced, and metastatic RCC.     

R-LESS Partial Nephrectomy Trifecta Outcome Is Inferior to Multiport Robotic Partial Nephrectomy: Comparative Analysis

Background

Trifecta achievement in partial nephrectomy (PN) is defined as the combination of warm ischemia time ≤20 min, negative surgical margins, and no surgical complications.

Objective

To compare trifecta achievement between robotic, laparoendoscopic, single-site (R-LESS) PN and multiport robotic PN (RPN).

Design, setting, and participants

Data from 167 patients who underwent RPN from 2006 to 2012 were retrospectively analyzed.

Outcome measurements and statistical analysis

Primary outcome measurement was trifecta achievement; secondary outcome was the perioperative and postoperative comparison between groups. The measurements were estimated and analyzed with SPSS v.18 using univariable, multivariable, and subgroup analyses.

Results and limitations

Eighty-nine patients were treated with RPN and 78 were treated with R-LESS PN. Baseline characteristics of both groups were similar. Trifecta was achieved in 38 patients (42.7%) in the multiport RPN group and 20 patients (25.6%) in the R-LESS PN group (p = 0.021). Patients in the R-LESS PN group had longer mean operative time, warm ischemia time, and increased estimated glomerular filtration rate (eGFR) percentage change. No significant differences were found between the two groups in days of hospitalization, blood loss, postoperative eGFR, positive surgical margins, and surgical complications. Patients with increased PADUA and RENAL scores, infiltration of the collecting system, and renal sinus involvement had an increased probability of not achieving the trifecta. In regression analysis, the type of procedure and the tumor size could predict trifecta accomplishment (p = 0.019 and 0.043, respectively). The retrospective study, the low number of series, and the controversial definition of trifecta were the main limitations.

Conclusions

The trifecta was achieved in significantly more patients who underwent multiport RPN than those who underwent R-LESS PN. R-LESS PN could be an alternative option for patients with decreased tumor size, low PADUA and RENAL scores, and without renal sinus or collecting system involvement.

Patient summary

In this study, we looked at the outcomes of patients who had undergone robotic partial nephrectomy. We found that conventional robotic partial nephrectomy is superior to R-LESS partial nephrectomy with regard to the accomplishment of negative margins, reduced warm ischemia time, and minimal surgical complications.     

Observation Should be Considered as an Alternative in Management of Renal Masses in Older and Comorbid Patients

Background

Renal masses diagnosed in older and comorbid patients represent a challenge with regard to treatment.

Objective

To evaluate clinical outcome and tumor progression in patients with renal masses managed by observation due to age and comorbidity.

Design, setting, and participants

The medical records of 63 consecutive patients with renal masses primarily managed by observation during 2002–2007 were reviewed retrospectively and analyzed. The mean age for all patients at diagnosis was 76.6 yr, and 59% were male. Mean tumor size was 4.3 cm in diameter at diagnosis. Of these, 30% had Eastern Cooperative Oncology Group performance status (PS) of 2 or 3, 78% were American Society of Anesthesiologists (ASA) class 3, and the patients had a mean of 2.8 other medical conditions.

Measurements

Registration of age, ASA class, PS, comorbid conditions, computed tomography scans, primary tumor size, tumor growth rate, pathology parameters, observation time, survival time.

Results and limitations

Five-year overall survival (OS) and cancer-specific survival (CSS) rates were 42.8% and 93.3%, respectively. For tumors ≤4.0 cm in size, 5-yr CSS was 100%. Nine patients received delayed radical treatment, none of whom had later progression of the disease. In 18 patients histopathologic diagnosis of the renal masses were available, and in 15 patients (83%) renal cell carcinoma (RCC) was verified. The annual growth rate was <1 cm/yr in 85.4% of the cases. In tumors ≤4.0 cm, only 1 of 27 tumors (3.7%) grew faster than 1 cm/yr.

Conclusions

Management of renal masses by observation among older and comorbid patients seems to give acceptable results with regard to OS and CSS rates after 5 yr. The risk of disease progression is significantly higher in patients with larger sized renal masses (>4 cm). Thus, selection for observation in this group has to be stricter than in a group of patients with smaller sized renal masses (≤4.0 cm).     

Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) Classification of Renal Tumours in Patients who are Candidates for Nephron-Sparing Surgery

Background

Besides clinical tumour size, other anatomical aspects of the renal tumour are routinely considered when evaluating the feasibility of elective nephron-sparing surgery (NSS).

Objective

To propose an original, standardised classification of renal tumours suitable for NSS based on their anatomical features and size and to evaluate the ability of this classification to predict the risk of overall complications resulting from the surgery.

Design, setting, and participants

We enrolled prospectively 164 consecutive patients who underwent NSS for renal tumours at a tertiary academic referral centre from January 2007 to December 2008.

Intervention

Open partial nephrectomy without vessel clamping.

Measurements

All tumours were classified by integrating size with the following anatomical features: anterior or posterior face, longitudinal, and rim tumour location; tumour relationships with renal sinus or urinary collecting system; and percentage of tumour deepening into the kidney. We generated an algorithm evaluating each anatomical parameter and tumour size (the preoperative aspects and dimensions used for an anatomical [PADUA] score) to predict the risk of complications.

Results and limitations

Overall rates of complication were significantly correlated to all the evaluated anatomical aspects, excluding clinical size and anterior or posterior location of the tumour. By multivariate analysis, PADUA scores were independent predictors of the occurrence of any grade complications (hazard ratio [HR] for score 8–9 vs 6–7: 14.535; HR for score ≥10 vs 6–7: 30.641). Potential limitations were the limited number of patients with T1b tumours included in the study and the lack of laparoscopically treated patients. Further external validation of the PADUA score is needed.

Conclusions

The PADUA score is a simple anatomical system that can be used to predict the risk of surgical and medical perioperative complications in patients undergoing open NSS. The use of an appropriate score can help clinicians stratify patients suitable for NSS into subgroups with different complication risks and can help researchers evaluate the real comparability among patients undergoing NSS with different surgical approaches.     

Integrating Surgery with Targeted Therapies for Renal Cell Carcinoma: Current Evidence and Ongoing Trials

Context

Surgical intervention is the primary treatment for early-stage renal cell carcinoma (RCC), but alone it has limited benefit in patients with metastatic disease. The advent of targeted agents for RCC has improved the outcome in these patients, and there is increasing interest in exploring the efficacy and safety of these agents in combination with surgery in both early and advanced disease.

Objective

This article reviews approved and emerging targeted therapies for RCC and outlines the rationale and implications for combining these therapies with surgery.

Evidence acquisition

A search of the literature, trial registries, and meeting proceedings was performed, and reports on surgery, receptor tyrosine kinase inhibitors, vascular endothelial growth factor antibodies, mammalian target of rapamycin inhibitors, and cytokine adjuvant therapy relating to RCC were critically reviewed.

Evidence synthesis

Nephrectomy has been shown to improve overall survival in patients with metastatic RCC (mRCC) treated with interferon alpha. Combining targeted therapy with surgery has the potential to improve efficacy and tolerability relative to cytokine therapy and prospective studies are underway. In the localized setting, there is some evidence of tumor downsizing with neoadjuvant targeted therapy. The tolerability and safety of targeted agents used perioperatively must be considered, particularly in the adjuvant setting where chronic therapy is required to prevent recurrence or metastasis. Novel agents with greater specificity and improved safety profiles are under development and have the potential to enhance efficacy and minimize the risk of complications.

Conclusions

For patients with mRCC, randomized controlled trials are ongoing to define the role and sequence of nephrectomy in combination with targeted therapy. Until data are available, nephrectomy remains part of the mRCC treatment algorithm for patients with good performance status and a resectable tumor. Targeted therapy to downsize large primary tumors in nonmetastatic disease is investigational, but the rate of surgically relevant down-staging and tumor shrinkage seen with the current generation of agents is limited. In patients with high-risk nonmetastatic disease, adjuvant therapy must be administered only in the context of the ongoing clinical trials since there are no data showing efficacy in this setting.     

Partial Nephrectomy Is Associated with Improved Overall Survival Compared to Radical Nephrectomy in Patients with Unanticipated Benign Renal Tumours

Background

Partial nephrectomy (PN) has been associated with improved overall survival (OS) in select cohorts with localised renal masses when compared to radical nephrectomy (RN). The driving forces behind these differences have been difficult to elucidate given the heterogeneity of previously compared cohorts.

Objective

Compare OS in a subset of patients with unanticipated benign renal masses to minimise the confounding effect of cancer.

Design, setting, and participants

We retrospectively evaluated 2608 consecutive clinical T1 enhancing renal masses that were treated with extirpative surgery at our institution between 1999 and 2006. Of these, 499 tumours (19%) were found to be benign on final pathology. Preoperative data and renal functional data were used to generate a propensity model that was then plugged into a multivariate model of survival. Median follow-up for the entire cohort was 50 mo (interquartile range [IQR]: 32–73).

Intervention

All patients underwent PN or RN.

Measurements

We measured OS and cardiac-specific survival.

Results and limitations

Five-year OS estimates for the PN (n = 388) and RN (n = 111) cohorts were 95% (95% confidence interval [CI], 93–98) versus 83% (95% CI, 74–90), respectively (P < 0.0001). On multivariate analysis, controlling for both comorbidity and age, RN was associated with a 2.5-fold increased risk of death compared to PN (hazard ratio [HR]: 2.5; 95% CI, 1.3–5.1). Postoperative estimated glomerular filtration rate (eGFR) was also an independent predictor of OS and cardiac-specific survival (HR: 0.97; 95% CI, 0.95–0.99 and HR: 0.96; 95% CI, 0.93–0.99, respectively). The retrospective nature of this analysis limits the strength of the conclusions.

Conclusions

PN was associated with better OS when compared to RN in patients with unanticipated benign tumours. This observed survival advantage appears partly to be the result of better preservation of eGFR, but other kidney functions or unmeasured factors may also play a role. These data indicate that PN should be aggressively pursued in any patient where PN is technically feasible.     

Simple Enucleation for the Treatment of PT1a Renal Cell Carcinoma: Our 20-Year Experience

Objectives

To evaluate the safety and efficacy of simple enucleation as a conservative treatment for pT1a RCC, and to report on the incidence of major complications, local recurrence, and progression-free and disease-specific survival rates.

Methods

We retrospectively reviewed the data of 232 patients who had nephron-sparing surgery (NSS) by simple enucleation between 1986 and 2004 for sporadic, unilateral, pathologically confirmed pT1a RCC. The patients’ status was evaluated last in September 2005. The mean (median, range) follow-up was 76 (61, 12–225) months.

Results

The mean (SD, median, range) tumor greatest dimension was 2.8 (0.78, 2.85, 0.6–4) cm. The histopathologic review according to the International Union Against Cancer and American Joint Commission for Cancer (1997) classification revealed 198 clear cell (85.3%), 18 papillary (7.8%), 15 chromophobe (6.5%) and one (0.4%) collecting duct RCCs. There were no major complications, such as prolonged acute tubular necrosis/chronic renal insufficiency and bleeding requiring open reoperation. One patient developed postoperative late retroperitoneal fluid collection consistent with urinoma, which required aspiration, drainage position and JJ stenting for 3 weeks. The 5- and 10-year cancer-specific survival were 96.7% and 94.7%, respectively. The 5- and 10-year progression-free survival were 96% and 94%, respectively. Overall, 13 (6.4%) patients had disease progression, three of whom had local recurrences alone (1.5%) elsewhere in the kidney; none had local recurrence at the level of the enucleation bed.

Conclusions

Simple tumor enucleation is a safe and acceptable nephron-sparing treatment that provides excellent long-term local control and cancer-specific survival rates.     

Systemic Treatment of Metastatic Clear Cell Renal Cell Carcinoma in 2018: Current Paradigms,Use of Immunotherapy,and Future Directions

Context

Systemic therapy for metastatic clear cell renal cell carcinoma (mccRCC) has greatly evolved over the last 15 yr. More recently, combination strategies involving contemporary immunotherapy have emerged as key opportunities to further shift the treatment landscape.

Progression-free Survival After Second Line of Therapy for Metastatic Clear Cell Renal Cell Carcinoma in Patients Treated with First-line Immunotherapy Combinations

Immunotherapy (IO)-based combinations used to treat metastatic clear cell renal cell carcinoma (ccRCC) include dual immune checkpoint inhibition with ipilimumab and nivolumab (IO/IO) and several combinations of vascular endothelial growth factor receptor–targeting tyrosine kinase inhibitors (TKIs) with an immune checkpoint inhibitor (TKI/IO). IO/IO and TKI/IO approaches have not been compared directly, and it is unknown whether patients who do not respond to first-line IO/IO can salvage long-term survival by receiving a second-line TKI. Progression-free survival after second-line therapy (PFS-2) evaluates the ability to be salvaged by second-line therapy. We retrospectively evaluated 173 patients treated with first-line IO/IO or TKI/IO for metastatic ccRCC at Memorial Sloan Kettering Cancer Center and report PFS-2, overall survival, and response to second line of therapy (ORR_2nd) for groups defined by first-line category. Although ORR_2nd was significantly higher with IO/IO than with TKI/IO (47% vs 13%, p < 0.001), there was no significant difference in median PFS-2 for TKI/IO versus IO/IO (44 vs 23 mo, log-rank p = 0.1) or restricted mean survival time (RMST) for PFS-2 when adjusted for propensity score (33 vs 30 mo; difference 2.6 mo [95% confidence interval {CI}: –2.6, 7.9]; p = 0.3). There was also no significant difference in RMST for overall survival when adjusted for propensity score (38 vs 37 mo; group difference 1.0 mo [95% CI: –3.4, 5.5]; p = 0.7). These findings do not support a change in current utilization practices for IO/IO and TKI/IO treatment strategies for ccRCC.Patient summaryIn cases of metastatic clear cell renal cell carcinoma, no significant difference was observed in progression-free survival after second line of therapy between patients receiving ipilimumab plus nivolumab and those receiving a combination of a tyrosine kinase inhibitor and an immune checkpoint inhibitor.     

Clinical Outcome in a Contemporary Series of Restaged Patients with Clinical T1 Bladder Cancer

Objectives

To evaluate the indications for early and deferred cystectomy and to report the impact of this tailored approach on survival.

Design, setting, and participants

We retrospectively studied 523 patients seen at our institution who were initially diagnosed with T1 disease between 1990 and 2007.

Measurements

Variables analyzed included age, gender, multifocality, multifocal T1 disease, carcinoma in situ, grade, recurrence rate, and restaging status. End points were overall and disease-specific survival.

Results and limitations

A restaging transurethral resection (TUR) was performed in 523 patients. Of the patients who underwent restaging, 106 (20%) were upstaged to muscle-invasive disease and 417 patients were considered true clinical T1 (cT1); 84 of the latter group underwent immediate cystectomy. The median follow-up for survivors was 4.3 yr. The cumulative incidence of disease-specific death at 5 yr was 8% (95% confidence interval [CI], 5–13%), 10% (95% CI, 5–17%), and 44% (95% CI, 35–56%) for those restaged with lower than T1, T1, and T2 disease, respectively. Immediate cystectomy was more likely in patients with cT1 disease at restaging than in those with disease lower than cT1, but there were no other obvious differences in clinical characteristics between those with and without immediate cystectomy. Survival was not statistically different for patients who underwent an immediate cystectomy versus those who were maintained on surveillance with deferred cystectomy if deemed appropriate. Of 333 patients who did not undergo immediate cystectomy, 59 had a deferred cystectomy, and the likelihood of deferred cystectomy was greater in those with T1 disease on restaging TUR (hazard ratio: 2.40; 95% CI, 1.43–4.01; p = 0.001).

Conclusions

Restaging TUR should be performed in patients diagnosed with cT1 bladder cancer to improve staging accuracy. Patients with T1 disease on restaging are at higher risk of progression and should be considered for early cystectomy.     

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.