Prognostic factors in a large multi-institutional series of papillary renal cell carcinoma

Study Type – Prognosis cohort series (multi‐centre) Level of Evidence 2b What's known on the subject? and What does the study add? The relatively low prevalence of papillary RCC and the limited number of patients enrolled in most of the surgical series limit meaningful conclusions with respect to cancer‐related outcome and independent prognostic information. Patients with papillary RCC have relatively a low risk of tumour recurrence and cancer‐related death after surgery. Pathological lymph node stage, presence of metastases and Fuhrman nuclear grade were the main independent predictors of cancer‐related outcomes, whereas only a non‐statistically significant trend was found for the 2009 pathological T stage.

OBJECTIVES

• ? To investigate cancer‐related outcomes and prognostic factors of papillary renal cell carcinoma (pRCC) in a large multicentre data set.
• ? Oncological outcome and prognostic factors of pRCC have been limitedly evaluated in comparison with the most common RCC subtype, clear cell RCC.

PATIENTS AND METHODS

• ? From a multicentre retrospective database, including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007, 577 patients with pRCC were identified.
• ? Univariable and multivariable Cox regression models were performed to identify prognostic factors predictive of recurrence‐free survival (RFS) and cancer‐specific survival (CSS) after surgery.

RESULTS

• ? At a median (interquartile range) follow‐up of 39.2 (21.7–72) months, 81 (14%) patients had experienced disease progression and 63 (11%) patients had died from disease; the 5‐year RFS estimate was 85.5%.
• ? In multivariable analysis, pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.9; P= 0.007) and Fuhrman nuclear grade (pooled P= 0.039) were all independent predictors of RFS; the 5‐year CSS estimate was 87.9%.
• ? In Cox multivariable analysis, an independent predictive role was reconfirmed for mode of presentation (pooled P= 0.038), pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.4; P= 0.049) and Fuhrman nuclear grade (pooled P= 0.037).

CONCLUSIONS

• ? Patients with pRCC have a low risk of tumour recurrence and cancer‐related death after surgery.
• ? Fuhrman nuclear grade was found to be a stronger predictor of both RFS and CSS, whereas only a non‐statistically significant trend was found for the 2009 pathological T stage.

     

Exposed proliferation antigen 210 (XPA-210) in renal cell carcinoma (RCC) and oncocytoma: clinical utility and biological implications

What's known on the subject? and What does the study add? The exposed proliferation antigen 210 (XPA‐210) of the proliferation marker thymidine kinase 1 (TK1) showed higher expression levels in metastatic renal cell carcinoma. The current study used a new XPA‐210 antibody to clarify the role of TK1 tissue expression in the largest reported cohort of different renal cell carcinoma types and oncocytomas.

OBJECTIVE

• ? To determine the clinical role of the exposed proliferation antigen 210 (XPA‐210) of the proliferation marker thymidine kinase 1 (TK1) in a large cohort of different renal cell carcinoma (RCC) types, oncocytomas and normal renal tissues samples, as TK1 is reported to be of clinical significance in several cancer entities and is suggested as a prognostic serum biomarker for RCC.

PATIENTS AND METHODS

• ? Expressions of XPA‐210 were determined immunohistochemically in 40 clear cell RCCs (ccRCC), 25 papillary RCCs (papRCC), 17 chromophobe RCC (chRCC), 27 oncocytomas and 64 normal renal parenchyma paraffin‐embedded specimens.
• ? Immunohistochemistry was performed with a monoclonal anti‐XPA‐210 antibody. Staining was measured by the percentage of positive cells.
• ? Expression was compared between subgroups and correlated with respective clinical data using one‐way analysis of variance with post hoc Tukey‐Kramer analyses.

RESULTS

• ? XPA‐210 staining in the RCC subgroup was significantly different from the oncocytomas (mean [sem ] 4.1 [0.4] vs 2.2 [0.4]; P = 0.004) and from normal renal tissue (1.0 [0.1]; P < 0.001], whereas oncocytomas did not differ from normal renal parenchyma staining (P = 0.18).
• ? Subdivided into RCC groups, only ccRCC (mean [sem ] 5.1 [0.6]; P < 0.001) and papRCC (4.4 [0.6]; P < 0.001) varied from normal renal parenchyma, whereas chRCC (1.4 [0.3]; P = 0.99) did not.
• ? RCC XPA‐210 staining was significantly associated with higher tumour stage (T = 3, P = 0.002) and grade (G = 3, P = 0.001).

CONCLUSIONS

• ? The malignant character of RCC is reflected by higher XPA‐210 expression as compared with oncocytomas and normal kidney.
• ? The ccRCC and papRCC subgroups had higher XPA‐210 levels.
• ? XPA‐210 could be considered a potential marker for the assessment of the proliferative activity in primary RCC.

     

Comparison of oncological outcomes of transperitoneal and retroperitoneal laparoscopic radical nephrectomy for the management of clear‐cell renal cell carcinoma: a multi‐institutional study

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Laparoscopic radical nephrectomy (LRN) can be performed by a retroperitoneal approach with similar efficacy compared to the transperitoneal approach. However, the oncological acceptance of LRN has been based on studies which have been carried out primarily by transperitoneal approach, and oncological results of the retroperitoneal approach alone are lacking. Our study confirmed that retroperitoneal laparoscopic radical nephrectomy is oncologically‐equivalent to transperitoneal approach in homogeneous group with the final pathological diagnosis of clear cell RCC.

OBJECTIVE

• ? To investigate the oncological efficacy of retroperitoneal laparoscopic radical nephrectomy (RLRN) compared with transperitoneal laparoscopic radical nephrectomy (TLRN) for the management of clear‐cell renal cell carcinoma (RCC).

PATIENTS AND METHODS

• ? With emphasis on survival and disease recurrence, a retrospective analysis was made of 580 patients who underwent TLRN (472 patients) or RLRN (108 patients) at 23 institutions between January 1997 and December 2007.
• ? Inclusion criteria were clear‐cell RCC, stage pT1 to pT2 without any nodal involvement, and metastasis.
• ? Overall survival and recurrence‐free survival curves were estimated using the Kaplan–Meier method.
• ? To assess the association between the surgical approach and survival outcomes, Cox proportional hazard models were constructed.

RESULTS

• ? The median follow‐up was 30 months in the TLRN group and 35.6 months in the RLRN group. Both groups were comparable regarding age, gender, body mass index (BMI), Fuhrman’s grade, size of tumours and stage.
• ? Kaplan–Meier curves and the log‐rank test showed no significant difference between the TLRN and RLRN groups in 5‐year overall (92.6% vs 94.5%; P = 0.669) and recurrence‐free survival (92.0% vs 96.2%; P = 0.244).
• ? In a Cox regression model with age, gender, Eastern Cooperative Oncology Group performance status, BMI, nuclear grade and T‐stage adjusted variables, no significant difference was found between the two surgical approaches.

CONCLUSION

• ? The present study is the largest oncological analysis for laparoscopic radical nephrectomy (LRN) comparing transperitoneal and retroperitoneal approaches. The data from it provide the objective evidence to suggest similar oncological outcomes for both approaches to LRN.

     

Clinical efficacy and prognostic factors for overall survival in Japanese patients with metastatic renal cell cancer treated with sunitinib

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? A randomized prospective phase III clinical trial for systemic treatment‐naïve metastatic renal cell cancer (RCC) patients demonstrated the superiority of sunitinib over interferon with an acceptable safety profile. However, a commonly asked question is whether patients with RCC in clinical trials are representative of those with this disease being seen in ordinary clinical practice. To our knowledge, this is the first report of sunitinib for the Japanese patients with metastatic RCC in ordinary clinical practice. The estimated median PFS and OS in this study were 9.3 and 32.2 months, respectively. The application of the MSKCC model distinctly separated OS curves (P < 0.001), suggesting that MSKCC prognostic factors might be still valid to predict survival in metastatic RCC in the era of molecular targeted therapy.

OBJECTIVES

• ? To report the treatment efficacy and safety profile of sunitinib for patients with metastatic renal cell carcinoma (RCC) in ordinary clinical practice.
• ? In addition, to investigate the prognostic clinicopathological factors in these patients.

PATIENTS AND METHODS

• ? The present study consisted of native Japanese patients with metastatic RCC, comprising 29 pretreated and 34 systemic treatment‐naïve patients.
• ? Univariate and multivariate analyses were performed by the log‐rank test and the Cox proportional hazards model, respectively.

RESULTS

• ? Estimated median progression‐free survival and overall survival (OS) were 9.3 months (95% confidence interval, CI, 5.0–13.7) and 32.2 months (95% CI, 24.4–40.0), respectively.
• ? Among the patients pretreated before sunitinib, two patients were treated with initialized systemic therapy with sorafenib and the remaining 27 were initialized with interferon‐α.
• ? The OS from the initial systemic therapy of the patients in pretreated groups was 79.6 months (95% CI, 14.6–144.5).
• ? The application of the Memorial Sloan‐Kettering Cancer Center model distinctly separated the OS curves (P < 0.001).
• ? The most common grade 3 adverse events were fatigue (53%), thrombocytopaenia (48%), hand‐foot syndrome (16%), anaemia (20%), hypertension (10%) and leucopaenia (9%), although these events were manageable and reversible.

CONCLUSIONS

• ? Sunitinib has a favourable efficacy/safety profile for Japanese metastatic RCC patients in clinical practice.
• ? The estimated median OS was >2 years with acceptable tolerability.
• ? The median OS from the initial systemic therapy of the pretreated patients was >6 years.
• ? Memorial Sloan‐Kettering Cancer Center prognostic factors still appear to be valid for predicting survival in metastatic RCC in the era of molecular targeted therapy.

     

Population‐based comparative effectiveness of nephron‐sparing surgery vs ablation for small renal masses

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Case series of patients undergoing various forms of ablation show that it is technically feasible and possible for ablation to achieve short‐ and intermediate‐term cancer‐specific survival rates similar to those of controls undergoing partial nephrectomy. This is the first well‐powered study with a controlled design to compare effectiveness between partial nephrectomy and ablation.

OBJECTIVE

• ? To determine, in a population‐based cohort, if disease‐specific survival (DSS) was equivalent in patients undergoing ablation vs nephron‐sparing surgery (NSS) for clinical stage T1a renal cell carcinoma (RCC).

PATIENTS AND METHODS

• ? A retrospective cohort study was performed using patients from the Surveillance, Epidemiology and End Results cancer registry with RCC < 4 cm and no evidence of distant metastases, who underwent ablation or NSS.
• ? Kaplan–Meier and Cox regression analyses were performed to determine if treatment type was independently associated with DSS.

RESULTS

• ? Between 1998 and 2007, a total of 8818 incident cases of RCC were treated with either NSS (7704) or ablation (1114).
• ? The median (interquartile range) follow‐up was 2.8 (1.2–4.7) years in the NSS group and 1.6 (0.7–2.9) years in the ablation group, although 10% of each cohort were followed up beyond 5 years.
• ? After multivariable adjustment, ablation was associated with a twofold greater risk of kidney cancer death than NSS (hazard ratio 1.9, 95% confidence interval 1.1–3.3, P= 0.02).
• ? Age, gender, marital status and tumour size were also significantly associated with outcome.
• ? The predicted probability of DSS at 5 years was 98.3% with NSS and 96.6% with ablation.

CONCLUSION

• ? After controlling for age, gender, marital status and tumour size, the typical patient presenting with clinical stage T1a RCC, who undergoes ablation rather than NSS, has a twofold increase in the risk of kidney cancer death; however, at 5 years the absolute difference is small, and may only be realized by patients with long life expectancies.

     

Significant impact of age at diagnosis on the prognosis of Japanese patients with pT1 renal cell carcinoma following surgical resection

Study Type – Prognosis (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Several parameters significantly associated with the prognosis of patients with small venal cell carcinoma (RCC) have been reported; however, the outcomes described in such studies are not totally consistent, and the majority of these studies were based on the data from Western populations. Age of diagnosis is a significant predictor of disease recurrence as well as overall survivals in Japanese patients with pT1 RCC following surgical resection; therefore, intensive follow‐up of older patients is necessary even for those with pT1 RCC.

OBJECTIVE

• ? To retrospectively review oncological outcomes following surgical resection in Japanese patients with pT1 renal cell carcinoma (RCC).

PATIENTS AND METHODS

• ? The present study included a total of 832 consecutive Japanese patients who underwent either radical or partial nephrectomy and were subsequently diagnosed as having localized pT1 RCC.
• ? The significance of several clinicopathological factors in their postoperative outcomes was analysed.

RESULTS

• ? The median (range) age of the 832 patients was 66 (31–90) years. Radical and partial nephrectomies were performed for 710 patients (85.3%) and 122 patients (14.7%), respectively. Distribution of pathological stage was pT1a in 582 patients (70.0%) and pT1b in 250 patients (30.0%).
• ? During the observation period (median 44 months, range 3–114 months), postoperative disease recurrence developed in 38 patients (4.6%) and death occurred in 34 (4.1%). The 5‐year recurrence‐free and overall survival rates were 93.6% and 94.1%, respectively.
• ? Of several factors examined, only age at diagnosis was identified as an independent predictor of both postoperative disease recurrence and overall survival in these patients. Furthermore, there were significant differences in the recurrence‐free and overall survivals among patient groups stratified by age at diagnosis.

CONCLUSION

• ? These findings suggest that age at diagnosis is a significant predictor of disease recurrence as well as overall survival in patients with pT1 RCC following surgical resection; therefore, intensive follow‐up of older patients is necessary even for those with pT1 RCC.

     

Three-dimensional tumour volume and cancer-specific survival for patients undergoing nephrectomy to treat pT1 clear-cell renal cell carcinoma

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The positive association of tumour size (largest tumour dimension on pathology review) and risk of RCC progression and survival following nephrectomy is well documented. Moreover, several clinicopathological scoring systems (i.e. nomograms and algorithms) have been developed to predict outcomes for surgically treated RCC patients and each of these includes tumour size as an independent predictor of RCC outcome. There is still the question of whether information on three‐dimensional tumour volume (cm³) can provide additional prognostic information, particularly among patients with small pT1 tumours where the range of tumour size is more limited. Our study demonstrates that increasing tumour volume is associated with a greater risk of RCC‐specific death in patients with pT1 ccRCC, with a more pronounced association in pT1a tumours specifically. In addition, we observed evidence that tumour volume may provide more accurate prognostic information than tumour size alone in pT1a patients. Tumour volume may add prognostic information specifically in pT1a RCC.

OBJECTIVE

• ? To address whether information on three‐dimensional tumour volume can provide additional prognostic information for patients with small, localized renal cell carcinoma (RCC) superior to tumour size alone.

PATIENTS AND METHODS

• ? We identified 955 patients treated with radical nephrectomy or nephron‐sparing surgery for unilateral, sporadic, pT1, pN0/NX, M0, non‐cystic clear‐cell RCC (ccRCC) between 1980 and 2004, including 515 pT1a patients and 440 pT1b patients.
• ? We estimated tumour volume using three tumour dimensions recorded on pathological analysis and the equation for the volume of an ellipsoid [π/6 (length × width × height)]. For tumour size alone, we used the maximum tumour diameter recorded on pathological analysis.
• ? Univariate and multivariable associations with RCC‐specific death were evaluated using Cox proportional hazards regression models summarized with hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS

• ? Among pT1a patients, the risk of RCC death associated with having a tumour volume above the median (HR = 4.55; 95% CI, 1.30–15.83; P= 0.018) was markedly higher than having a tumour size above the median (HR = 2.55; 95% CI 0.83–7.85; P= 0.10).
• ? Comparison of concordance (c) index values further supported the idea that additional prognostic information was provided by tumour volume (c= 0.659) compared with tumour size (c= 0.600) for pT1a patients.
• ? Among pT1b patients, we noted that associations of tumour volume and tumour size with RCC‐specific death were similar.
• ? Multivariable adjustment did not alter our findings.

CONCLUSIONS

• ? Tumour volume could provide valuable prognostic information for patients with pT1a ccRCC but not pT1b ccRCC.
• ? Future investigations are needed to confirm this finding, explore other RCC subtypes and evaluate accuracy of tumour volume determination on radiographic imaging for potential patient management before surgery.

     

Unclassified renal cell carcinoma: a report of 56 cases

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Unclassified RCC represents 0.7–5.7% of renal tumours. Limited reported data from two series suggests that unclassified RCC is an aggressive form of RCC, mainly because most cases are at an advanced stage at presentation, but overall and cancer‐specific survival were not significantly different between unclassified and clear‐cell RCC in an additional series of 38 patients. Our study of 56 cases of unclassified RCC describes the pathological features that can be applied to predict prognosis on a daily basis. In particular nuclear grade, TNM classification, tumour coagulative necrosis, tumour size, microvascular invasion and 2004 WHO histotype are independent predictors of disease‐free and cancer‐specific survival.

OBJECTIVE

• ? To evaluate the clinicopathological features and outcomes of 56 patients with unclassified renal cell carcinoma (RCC) meeting 2004 World Health Organization diagnostic criteria.

PATIENTS AND METHODS

• ? Urological pathology files of the participating institutions were reviewed and cases of unclassified RCC that met the inclusion criteria were retrieved.
• ? Nuclear grade, pT status, tumour size, regional lymph node involvement, distant metastases, coagulative tumour necrosis, mucin and sarcomatoid differentiation were evaluated in radical nephrectomy or nephron‐sparing specimens.
• ? Significant factors in univariate analysis were then assessed by a multivariate analysis of independent prognostic factors using Cox proportional hazard regression analysis.

RESULTS

• ? Fifty‐six cases met the histological criteria for unclassified RCC. Thirty‐four (61%) cases were categorized as unrecognizable cell type (mean overall survival 47 months; median 36 months), 20 (36%) as composites of recognized types (mean overall survival 36 months; median 26 months), and two (4%) (mean survival 16 months; median 16 months) as pure sarcomatoid morphology without recognizable epithelial elements.
• ? Cox multivariate analysis showed nuclear grade (P= 0.020), stage (P < 0.001), tumour coagulative necrosis (P= 0.018), tumour size (P < 0.001), microvascular invasion (P < 0.001) and tumour histotype (P= 0.028) to be independent predictors of disease‐free survival, with tumour size being the most significant (hazard ratio [HR] 9.068, 95% confidence interval [CI] 3.231–25.453).
• ? Nuclear grade (P= 0.026), stage (P < 0.001), tumour coagulative necrosis (P < 0.001), tumour size (P= 0.044), microvascular invasion (P < 0.001), tumour recurrence after surgery (P < 0.001) and tumour histotype (P= 0.056) were independent predictors of cancer‐specific survival, with tumour recurrence after surgery being the most significant (HR 14.713, 95% CI 5.329–40.622).

CONCLUSION

• ? The prognosis of patients with unclassified RCC seems to be related to clinicopathological features known to be relevant in common forms of RCC.

     

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

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.

     

Limitations of preoperative biopsy in patients with metastatic renal cell carcinoma: comparison to surgical pathology in 405 cases

Study Type – Diagnostic (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Although there have been many investigations of biopsy for small renal masses, there are scant data on the accuracy of biopsy in the setting of metastatic renal cell carcinoma (mRCC). We report a large series of biopsies and compare with nephrectomy pathology in patients with mRCC. The present study highlights the inaccuracy of biopsy in the setting of metastatic disease, which is related to sampling error because of heterogeneity within the tumour and among metastases. These limitations are important to realize when designing trials that depend on pathological findings from biopsy and not nephrectomy. In addition, we found that biopsy of primary tumours were more likely than biopsy of metastatic sites to be diagnostic of RCC. Future studies with multiquadrant biopsies of primary tumours could yield the most accurate pathological results for future studies.

OBJECTIVE

• ? To evaluate the ability of preoperative biopsy to identify high‐risk pathological features by comparing pathology from preoperative metastatic site and primary tumour biopsies with nephrectomy pathology in patients with metastatic renal cell carcinoma (mRCC).

PATIENTS AND METHODS

• ? We reviewed clinical and pathological data from patients who underwent biopsy before cytoreductive nephrectomy for mRCC at MD Anderson Cancer Center (MDACC) from 1991 to 2007.
• ? Percutaneous biopsy techniques included fine‐needle aspiration, core needle biopsy or a combination of both techniques.

RESULTS

• ? The pathology of 405 preoperative biopsies (239 metastatic site, 166 primary tumour) from 378 patients was reviewed at MDACC before cytoreductive nephrectomy.
• ? The biopsy and nephrectomy specimens had the same histological subtype in 96.0% of clear‐cell renal cell carcinomas (RCCs) and 72.7% of non‐clear‐cell RCCs.
• ? Of 76 nephrectomy specimens where sarcomatoid de‐differentiation was identified, only seven (9.2%) were able to be identified from the preoperative biopsy.
• ? In 38.3% of patients, the same Fuhrman grade was identified in both the biopsy and nephrectomy specimens.
• ? A definitive diagnosis of RCC was more likely to be reported in primary tumour biopsies than in metastatic site biopsies. (P < 0.001).

CONCLUSIONS

• ? Preoperative biopsy has limited ability to identify non‐clear‐cell histological subtype, Fuhrman grade or sarcomatoid features.
• ? When surgical pathology is not available, a biopsy obtaining multiple samples from different sites within the primary tumour should be recommended rather than limited metastatic site biopsy to identify patients for clinical trials.

     

Use of tyrosine kinase inhibitors in patients with metastatic kidney cancer receiving haemodialysis: a retrospective Italian survey

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Sunitinib and sorafenib are orally administered multikinase inhibitors approved for the treatment of advanced RCC. The limited pharmacokinetics data on sunitinib and sorafenib suggest that haemodialysis does not significantly alter plasma concentrations. In this retrospective study we define the safety and efficacy of tyrosine kinase inhibitors in patients with metastatic RCC (mRCC) and end‐stage renal disease requiring haemodialysis. Even though the retrospective nature of this survey and the relatively small sample size represent major limitations, these data indicate that treatment with sunitinib and sorafenib in this cohort of patients is feasible with no unexpected toxicity and good efficacy, results similar to those in the general population of patients with mRCC.

OBJECTIVE

• ? To investigate the safety and efficacy of tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) and end‐stage renal disease requiring haemodialysis (HD).

PATIENTS AND METHODS

• ? Between July 2006 and December 2010, 24 patients undergoing HD were treated with sunitinib and/or sorafenib for mRCC in 14 Italian institutions.
• ? We retrospectively reviewed the medical records of these patients to evaluate the administered doses of TKIs, treatment‐related toxicities and the clinical response to therapy.

RESULTS

• ? Sunitinib was administered at 50 mg daily for 4–6 weeks in six patients, 37.5 mg daily for 4–6 weeks in seven patients (one patient subsequently increased the dose to 50 mg daily), 25 mg daily for 4–6 weeks in two patients and 12.5 mg daily for 4–6 weeks in one patient. Among the eight patients treated with sorafenib, four patients received 800 mg daily (400 mg every 12 h), three patients 400 mg daily and one patient 200 mg daily with a continuous schedule.
• ? The estimated median progression‐free and overall survival periods of this cohort of patients were 10.3 months and 22.6 months, respectively.
• ? With regard to tolerability and safety, no unexpected adverse events were registered and no grade 4 haematological or non‐haematological toxicities were reported.

CONCLUSIONS

• ? Sunitinib and sorafenib treatment is not contraindicated in patients with mRCC undergoing HD.
• ? The outcome of this patient population is similar to that observed in patients with normal renal function treated with TKIs.
• ? These results merit further confirmation by a larger prospective trial.

     

Laparoscopic partial nephrectomy for multiple tumours: feasibility and analysis of peri-operative outcomes

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Laparoscopic nephron‐sparing procedures have been increasingly utilized. However, in the presence of multiple tumours the procedure choice is usually shifted to radical nephrectomy. In view of favourable perioperative outcomes, the benefits of minimally‐invasive, nephron‐sparing surgery in experienced hands could be safely extended to patients presenting with multiple ipsilateral renal masses.

OBJECTIVE

• ? To describe our experience with laparoscopic partial nephrectomy (LPN) for multiple kidney tumours and compare the outcomes with LPN performed for single masses.

PATIENTS AND METHODS

• ? Retrospective analysis of medical records of patients undergoing LPN at our institution between 2005 and 2009 was performed.
• ? The cohort was divided in two groups based on tumour focality: group 1, LPN for a single tumour (n= 99) and group 2, LPN for multiple ipsilateral tumours (n= 12).
• ? The groups were compared with regards to demographic and peri‐operative variables.

RESULTS

• ? Demographic variables were not different between the groups. Median dominant tumour size was 3.1 cm (interquartile range [IQR] 2.4–4.0) and 4.0 cm (2.3–5.9) in groups 1 and 2, respectively.
• ? Median secondary tumour size in group 2 was 1.0 cm (1.0–1.8).
• ? Operative times were longer in group 2 compared with group 1 (220 vs 160 min, P= 0.009).
• ? Warm ischaemia times (WIT) (23 vs 22 min) and estimated blood loss (EBL) (100 vs 85 mL) were similar.

CONCLUSIONS

• ? LPN is a viable option for the treatment of multiple ipsilateral renal tumours.
• ? Peri‐operative outcomes are similar to standard LPN with the exception of longer operative time.
• ? In experienced hands, the advantages of minimally invasive surgery may be extended to select patients with ipsilateral multifocal renal tumours.

     

Chromophobe renal cell carcinoma (RCC): oncological outcomes and prognostic factors in a large multicentre series

Study Type – Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? About 80% of RCCs have clear cell histology, and consistent data are available about the clinical and histological characteristics of this histological subtype. Conversely, less attention has been dedicated to the study of non‐clear cell renal tumours Specifically, published data show that chromophobe RCC (ChRCC) have often favourable pathological stages and better nuclear grades as well as a lower risk of metastasizing compared with clear cell RCC (ccRCC). Patients with ChRCC were shown to have significantly higher cancer‐specific survival (CSS) probabilities compared with ccRCC. However, an independent prognostic role of RCC histotype was not confirmed in some large multicenter series and only a few studies have focused on the oncological outcomes of ChRCC. The present study is one of the few to evaluate cancer‐related outcomes of ChRCC and represents to our knowledge the largest series of ChRCCs. Consequently, the present findings may assist in elucidating the natural history of surgically treated ChRCC. The present study confirms that ChRCCs have good prognosis and a low tendency to progress and metastasize. Only 1.3% of patients presented with distant metastases at diagnosis, and the 5‐ and 10‐year CSS were 93% and 88.9%, respectively. However, although ChRCCs are generally characterised by an excellent prognosis, we observed that patients with locally advanced or metastatic cancers as well as those with sarcomatoid differentiation have a poor outcome. The study also investigated prognostic factors for recurrence‐free survival (RFS) and CSS for this RCC histotype. The definition of outcome predictors can be useful for patient counselling, planning of follow‐up strategies, and patient selection for clinical trials. In the present study, gender, clinical T stage, pathological T stage, and presence of sarcomatoid differentiation were significantly associated with RFS and CSS at multivariable analysis. We also identified N/M stage as an independent predictor of CSS. Notably, as Fuhrman grade was not an independent predictor of cancer‐related outcomes, the present study confirms that this histological variable is not a reliable prognostic factor for ChRCC.

OBJECTIVES

• ? To investigate cancer‐related outcomes of chromophobe renal cell carcinoma (ChRCC) in a large multicentre dataset.
• ? To determine prognostic factors for recurrence‐free survival (RFS) and cancer‐specific survival (CSS) for this RCC histological type.

PATIENTS AND METHODS

• ? In all, 291 patients with ChRCC were identified from a multi‐institutional retrospective database including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007.
• ? Univariable and multivariable Cox regression models were used to identify prognostic factors predictive of RFS and CSS after surgery for ChRCC.

RESULTS

• ? At a median follow‐up of 44 months, 25 patients (8.6%) had disease recurrence and 18 patients (6.2%) died from disease.
• ? The 5‐year RFS and CSS rates were 89.3% and 93%, respectively.
• ? Gender (P= 0.014), clinical T stage (P= 0.017), pathological T stage (P= 0.003), and sarcomatoid differentiation (P= 0.032) were independent predictors of RFS at multivariable analysis.
• ? For CSS, there was an independent prognostic role for gender (P= 0.032) and T stage (P= 0.019) among the clinical variables and for T stage (P= 0.016), N/M stage (P= 0.023), and sarcomatoid differentiation (P= 0.015) among the pathological variables.

CONCLUSIONS

• ? Patients with ChRCC have a low risk of tumour progression, metastasis, and cancer‐specific death.
• ? Patient gender, clinical and pathological tumour stage, and sarcomatoid differentiation are significant predictors of RFS and CSS for ChRCC.

     

Upper urinary tract transitional cell carcinoma: location is not correlated with prognosis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Tumour location has been shown to be of prognostic importance in UUT‐TCC, with tumours of renal pelvis having a better prognosis than ureteral tumours. Patients from Balkan Endemic Nephropathy (BEN) areas had a higher frequency of pelvis tumours. Also, we found that belonging to a BEN area is an independent predictor of disease recurrence.

OBJECTIVE

• ? To identify the impact of tumour location on the disease recurrence and survival of patients who were treated surgically for upper urinary tract transitional cell carcinoma (UUT‐TCC).

PATIENTS AND METHODS

• ? A single‐centre series of 189 consecutive patients who were treated surgically for UUT‐TCC between January 1999 and December 2009 was evaluated.
• ? Patients who had previously undergone radical cystectomy, preoperative chemotherapy or contralateral UUT‐TCC were excluded.
• ? In all, 133 patients were available for evaluation. Tumour location was categorized as renal pelvis or ureter based on the location of the dominant tumour.
• ? Recurrence‐free probabilities and cancer‐specific survival were estimated using the Kaplan–Meier method and Cox regression analyses.

RESULTS

• ? The 5‐year recurrence‐free and cancer‐specific survival estimates for the cohort in the present study were 66% and 62%, respectively.
• ? The 5‐year bladder‐only recurrence‐free probability was 76%. Using multivariate analysis, only pT classification (hazard ratio, HR, 2.46; P= 0.04) and demographic characteristics (HR, 2.86 for areas of Balkan endemic nephropathy, vs non‐Balkan endemic nephropathy areas; 95% confidence interval, 1.37–5.98; P= 0.005) were associated with disease recurrence
• ? Tumour location was not associated with disease recurrence in any of the analyses.
• ? There was no difference in cancer‐specific survival between renal pelvis and ureteral tumours (P= 0.476).
• ? Using multivariate analysis, pT classification (HR, 8.04; P= 0.001) and lymph node status (HR, 4.73; P= 0.01) were the only independent predictors associated with a worse cancer‐specific survival.

CONCLUSION

• ? Tumour location is unable to predict outcomes in a single‐centre series of consecutive patients who were treated with radical nephroureterectomy for UUT‐TCC.

     

The operative safety and oncological outcomes of laparoscopic nephrectomy for T3 renal cell cancer

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Laparoscopic radical nephrectomy is a well established treatment for localized RCC, where nephron‐sparing approaches are not appropriate. As surgeon and departmental experience grow more extensive tumours will be tackled laparoscopically. However, little is known about the operative safety and oncological outcomes of the laparoscopic approach for locally advanced RCC. The present study describes the largest reported cohort of patients receiving laparoscopic radical nephrectomy for locally advanced RCC. In the context of suitably experienced personnel in an established centre, we have established that this approach is safe from operative, postoperative and oncological standpoints, with comparable data to existing open series.

OBJECTIVE

• ? To determine the operative, postoperative and oncological outcomes of laparoscopic radical nephrectomy (LRN) for locally advanced renal cell cancer (RCC), which, as surgeon and departmental experience increases, is being performed more often.

PATIENTS AND METHODS

• ? In total, 94 consecutive patients receiving LRN for pathologically confirmed T3 or T4 RCC at a tertiary referral centre between March 2002 and May 2010 were analyzed.
• ? Preoperative, operative, tumour and postoperative characteristics were evaluated together with recurrence and outcome data.
• ? Survival was estimated using the Kaplan–Meier method. Cox's proportional hazards model was used for multivariate analysis.

RESULTS

• ? In total, 77 patients had LRN with curative intent and 17 patients had LRN with cytoreductive intent.
• ? There were six LRNs (6.4%) that were converted to open procedures.
• ? Overall, there were two (2.1%) Clavien grade IIIa complications, one (1.1%) grade IVa complication and one (1.1%) postoperative death.
• ? Overall median follow‐up was 17.4 months. In total, 22 (28.6%) patients receiving curative LRN developed a recurrence after a median of 13.9 months; 12 (54.5%) patients developed distant metastases, five (22.7%) patients had local recurrences and three (13.6%) patients had transcoelomic spread. Median predicted progression free survival was 48.4 months in patients undergoing LRN with curative intent. Median predicted overall survival was 65.6 months after curative LRN and 15.7 months after cytoreductive LRN.
• ? Multivariate analysis did not reveal any variables influencing recurrence or survival.

CONCLUSIONS

• ? In the context of suitably experienced personnel in an established centre, LRN for locally advanced RCC is safe from an operative and oncological standpoint.
• ? Patients clinically staged as T3 RCC must still be selected carefully for LRN in a multidisciplinary setting.

     

Under-grading of <4 cm renal masses on renal biopsy

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? It is well documented that biopsy of small renal masses is inaccurate and tends to under‐estimate tumour grade compared with surgical specimens. To our knowledge there has not been a study showing grading discrepancy between biopsy and surgical excision in a large population‐based cohort.

OBJECTIVE

• ? To determine whether differences exist in tumour grade between patients who undergo partial nephrectomy (PN) and those who undergo ablation for renal tumours.

PATIENTS AND METHODS

• ? Data was obtained using the Surveillance, Epidemiology and End Results database. Patients with solitary renal tumours of <4 cm treated with ablation or PN and with renal cell carcinoma (RCC) histopathology were identified.
• ? Tissue diagnosis in the ablation specimens was obtained from biopsy reports, whereas tissue from PN specimens was determined from surgical pathology.
• ? Variables analysed included: year of diagnosis, age, sex, race/ethnicity, marital status, population density, education, poverty level, and tumour size.
• ? Stacked bar graphs were created to compare the distributions of grade and histology between the groups. Multinomial logistic regression was used to determine factors independently associated with grade.

RESULTS

• ? In all, 7704 (87.4%) patients underwent PN and 1114 (12.6%) underwent either radiofrequency ablation or cryoablation.
• ? The PN patients were younger at diagnosis (59 vs 68 years, P < 0.001), more likely to be married (70% vs 64%, P < 0.001), and had smaller tumours (2.4 vs 2.6 cm, P < 0.001).
• ? There were no differences in the distribution of histology between the PN and ablation groups.
• ? Tumour grade was significantly lower in tumours treated with ablation.
• ? Compared with grade 1 disease, those undergoing ablation were 30% less likely to have grade 2 (P < 0.001), 30% less likely to have grade 3 (P < 0.001), and 92% less likely to have grade 4 disease (P < 0.01) than those having PN.

CONCLUSIONS

• ? There is a strong association between grade and treatment type in patients with small renal masses after controlling for baseline characteristics.
• ? As grade is determined by different methods, we think that this shows systematic under‐grading in biopsy of small renal masses.

     

Survival after partial and radical nephrectomy for the treatment of stage T1bN0M0 renal cell carcinoma (RCC) in the USA: a propensity scoring approach

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Partial nephrectomy has become the standard of care for T1a renal tumours, and the application of nephron‐sparing techniques has increasingly been expanded to patients with localized T1b cancers. However, the relative efficacy of partial versus radical nephrectomy for these medium‐sized tumours has yet to be definitively established. This study employs a propensity scoring approach within a large US population‐based cohort to determine that no survival differences exist among patients with T1b renal tumours undergoing partial versus radical nephrectomy.

OBJECTIVES

• ? To compare survival after partial nephrectomy (PN) vs radical nephrectomy (RN) among patients with stage TIb renal cell carcinoma (RCC) using a propensity scoring approach.
• ? Propensity score analysis is a statistical methodology that controls for non‐random assignment of patients in observational studies.

PATIENTS AND METHODS

• ? Using the Surveillance, Epidemiology, and End Results registry, 11 256 cases of RCCs of 4–7 cm that underwent PN or RN between 1998 and 2007 were identified.
• ? Propensity score analysis was used to adjust for potential differences in baseline characteristics between patients in the two treatment groups.
• ? Overall survival (OS) and cancer‐specific survival (CSS) of patients undergoing PN vs RN was compared in stratified and adjusted analysis, controlling for propensity scores.

RESULTS

• ? In all, 1047 (9.3%) patients underwent PN. For the entire cohort, no difference in survival was found in patients treated with PN as compared with RN, as shown by the adjusted hazard ratio (HR) for OS (1.10; 95% confidence interval [CI]: 0.91–1.36) and renal‐CSS (HR 0.91; 95% CI: 0.65–1.27).
• ? When the cohort was stratified by tumour size and age, no difference in survival was identified between the groups.

CONCLUSIONS

• ? Even when stratified by tumour size and age, a survival difference between PN and RN in a propensity‐adjusted cohort of patients with T1b RCC could not be confirmed.
• ? If validated in prospective studies, PN may become the preferred treatment for T1b renal tumours in centres experienced with nephron‐sparing surgery.

     

Association of RASSF1A genotype and haplotype with the progression of clear cell renal cell carcinoma in Japanese patients

What's known on the subject? and What does the study add? Ras association domain family 1A (RASSF1A) is a tumour suppressor and regulates cell cycle, apoptosis and microtubule stability. This is the first study to identify associations between RASSF1A polymorphisms and clinicopathological parameters and survival in patients with clear cell renal cell carcinoma (CCRCC). RASSF1A genotyping may be useful for predicting the prognosis of the clinical course of CCRCC, and this finding might provide a better understanding of the mechanism underlying the development and progression of CCRCC. However, functional and prospective studies with a larger number of patients are needed to confirm the results.

OBJECTIVE

• ? To compare Ras association domain family 1A (RASSF1A) genotypes or haplotypes with clinicopathological characteristics and survival rates of patients with clear cell renal cell carcinoma (CCRCC).

PATIENTS AND METHODS

• ? The study cohort comprised 224 Japanese patients who underwent radical nephrectomy and had CCRCC confirmed by histopathological analysis.
• ? Three common polymorphisms in the RASSF1A gene, 133Ala/Ser (G/T), ‐710C/T and ‐392C/T, were genotyped using TaqMan assays and haplotypes were analysed using appropriate software.

RESULTS

• ? Patients with CCRCC with RASSF1A ‐710TT genotype exhibited a significantly higher tumour stage and higher stage grouping than those with ‐710CC or ‐710CT (P = 0.005 and P = 0.032, respectively).
• ? There was no significant association between 133Ala/Ser or ‐392C/T genotype and clinicopathological characteristics.
• ? RASSF1A 133Ala‐710T‐392T haplotype and ‐710TT genotype were significantly associated with poorer recurrence‐free survival rates (P = 0.038 and P = 0.007, respectively).

CONCLUSIONS

• ? This is the first study to identify associations between RASSF1A polymorphisms and clinicopathological parameters and survival in patients with CCRCC.
• ? RASSF1A genotyping may be useful in predicting the prognosis of the clinical course of CCRCC, and this finding might provide a better understanding of the mechanism underlying the development and progression of CCRCC.
• ? Functional and prospective studies with a larger number of patients are needed to confirm the results.