EAU guidelines on renal cell carcinoma: the 2010 update. Systemic Therapy for Non-Clear Cell Renal Cell Carcinoma. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Multicenter phase II study of sunitinib in patients with non-clear cell renal cell carcinoma. Randomized trial of adjuvant thalidomide versus observation in patients with completely resected high-risk renal cell carcinoma. Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma. Combination transurethral resection, systemic chemotherapy, and pelvic radiotherapy for invasive (T2-T4) bladder cancer unsuitable for cystectomy: a phase I/II Southwestern Oncology Group study. Improved prognostication of renal cell carcinoma using an integrated staging system. Autologous CIK Cell Immunotherapy in Patients with Renal Cell Carcinoma after Radical Nephrectomy A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma. Bladder cancer – the neglected tumor: a descriptive analysis of publications referenced in MEDLINE and data from the register clinicaltrials.gov Cytokine induced killer cell-based immunotherapies in patients with different stages of renal cell carcinoma. Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma. Organ-sparing treatment of invasive transitional cell bladder carcinoma. Phase II trial of everolimus for the treatment of nonclear-cell renal cell carcinoma. Active surveillance of small renal masses: progression patterns of early stage kidney cancer. Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy.
CONTEXT AND OBJECTIVES The European Association of Urology Guideline Group for renal cell carcinoma ( RCC ) has prepared these guidelines to help clinicians assess the current evidence -based management of RCC and to incorporate the present recommendations into daily clinical practice . EVIDENCE ACQUISITION The recommendations provided in the current up date d guidelines are based on a thorough review of available RCC guidelines and review articles combined with a systematic literature search using Medline and the Cochrane Central Register of Controlled Trials . EVIDENCE SYNTHESIS A number of recent prospect i ve r and omised studies concerning RCC are now available with a high level of evidence , whereas earlier publications were based on retrospective analyses , including some larger multicentre validation studies , meta-analyses , and well- design ed controlled studies . CONCLUSIONS These guidelines contain information for the treatment of an individual patient according to a current st and ardised general approach . Up date d recommendations concerning diagnosis , treatment , and follow-up can improve the clinical h and ling of patients with RCC Treatment options for metastatic clear cell renal cell carcinoma ( ccRCC ) have evolved markedly over the past decade , with multiple targeted therapies approved for the disease . In contrast , little improvement has been made in the management of metastatic non-clear cell RCC ( nccRCC ) . Non-clear cell disease is an umbrella term that encompasses multiple biologically distinct entities , including but not limited to papillary , chromophobe , and sarcomatoid RCC . To date , prospect i ve studies have largely explored treatments for ccRCC ( e.g. , VEGF- and mTOR-directed therapies ) in trials that aggregate non-clear cell histologies . However , the studies do not acknowledge the varying biology of each non-clear cell subtype . Emerging studies in nccRCC should examine individual histologies and apply biologically relevant therapies . An example of this is SWOG 1500 , a r and omized phase II study that will compare a  VEGF-inhibitor  to one of three  MET-directed therapies  in patients with metastatic papillary RCC . Until the biologic diversity of nccRCC is appreciated , outcomes are likely to remain dismal BACKGROUND The European Advanced Renal Cell Carcinoma Sorafenib ( EU-ARCCS ) exp and ed-access study provided sorafenib to advanced renal cell carcinoma ( RCC ) patients in whom previous systemic therapy had failed . The study assessed the safety and use of sorafenib for the treatment of advanced RCC in a large community-based patient population across 11 countries in Europe . PATIENTS AND METHODS EU-ARCCS was a single-arm , open-label trial of  sorafenib in advanced RCC patients . End points included safety , time to progression , progression-free survival ( PFS ) , and disease control rate ( DCR ) . Subgroup analyses included age , Eastern Cooperative Oncology Group performance status , histology , prior therapy , and number and sites of metastases . RESULTS About 1159 advanced RCC patients were enrolled . Most patients ( 94 % ) experienced drug-related adverse events ( AEs ) of any grade , with the most common grade ≥3 AEs including h and -foot skin reaction ( 13 % ) , diarrhea ( 7 % ) , fatigue ( 7 % ) , hypertension ( 6 % ) , and rash/desquamation ( 5 % ) . The incidence of AEs in the subgroups was similar to that in the overall population . Median PFS was 6.6 months ; DCR at ≥8 and ≥12 weeks was 85 % and 78 % , respectively . CONCLUSIONS The sorafenib safety profile in European community-based practice setting s was similar to that reported in clinical trials . The heterogeneous advanced RCC patient population in EU-ARCCS permitted assessment of sorafenib in important sub population s of advanced RCC patients BACKGROUND Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma ( nccRCC ) . PATIENTS AND METHODS Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes . Patients were treated with 50 mg/day oral sunitinib for 4 weeks , followed by 2 weeks of rest . The primary end point was overall response rate ( RR ) . RESULTS Thirty-one eligible patients were enrolled . Twenty-four patients ( 77 % ) had prior nephrectomy . By Memorial Sloan-Kettering Cancer Center criteria , 8 patients ( 26 % ) had poor risk and 14 ( 45 % ) had intermediate risk . Twenty-two patients had papillary renal cell carcinoma ( RCC ) , and three had chromophobe RCC . Eleven patients had partial response with a RR of 36 % ( 95 % confidence interval ( CI ) 19 % to 52 % ) and an additional 17 patients ( 55 % ) had stable disease . Median duration of response was 12.7 months ( 95 % CI 6.3 - 19.1 months ) , and median progression-free survival was 6.4 months ( 95 % CI 4.2 - 8.6 months ) . At a median follow-up duration of 18.7 months ( 95 % CI 13.7 - 23.7 months ) , 13 patients ( 42 % ) had died , result ing in an estimated median survival of 25.6 months ( 95 % CI 8.4 - 42.9 months ) . Toxicity profiles were commensurate with prior reports . CONCLUSIONS Sunitinib has promising activity in patients with nccRCC ( NCT01219751 ) OBJECTIVES To evaluate the effect of adjuvant thalidomide on recurrence-free survival ( RFS ) after nephrectomy for high-risk metastatic renal cell carcinoma ( RCC ) . METHODS Eligibility criteria for enrollment on this r and omized trial included any histologic subtype , T2 ( high grade , any N ) , T3/T4 ( any grade , any N ) , or node-positive ( any grade , any T ) RCC . We r and omized eligible patients to observation or to receive thalidomide 300 mg daily for 24 months . Patients were observed until disease recurrence or death . RESULTS After we enrolled 46 patients , we stopped the trial at a median follow up of 43.9 months ( range , 9.7 - 74.2 months ) . Patients on the thalidomide arm had inferior 2- and 3-year probabilities of RFS , compared with controls ( 47.8 % vs 69.3 % and 28.7 % vs 69.3 % , respectively ; P = .022 ) . The 2- and 3-year cancer-specific survival was similar for both groups . All observed deaths were attributable to RCC ( P = .392 ) . By multivariate analysis , tumor size and grade predicted recurrence ( P = .001 and .013 ) and kidney cancer-specific death ( P = .002 and .014 ) . Thalidomide treatment , however , was not an independent predictor of recurrence or cancer-specific mortality . CONCLUSIONS In this small , r and omized , controlled trial , adjuvant thalidomide therapy after complete resection of high-risk RCC did not improve the 2- and 3-year RFS rates or cancer-specific death rates Purpose The decreased effectiveness of single-agent targeted therapies in advanced non-clear cell renal cell carcinoma ( ncRCC ) compared with clear cell renal cell carcinoma ( RCC ) supports the study of combination regimens . We evaluated the efficacy of everolimus plus bevacizumab in patients with metastatic ncRCC . Patients and Methods In this single-center phase II trial , treatment-naive patients received everolimus 10 mg oral once per day plus bevacizumab 10 mg/kg intravenously every 2 weeks . The primary end point was progression-free survival ( PFS ) at 6 months . Correlative analyses explored c and i date tissue biomarkers through next-generation sequencing . Results Thirty-five patients were enrolled with the following histologic subtypes : chromophobe ( n = 5 ) , papillary ( n = 5 ) , and medullary ( n = 2 ) RCC and unclassified RCC ( uRCC , n = 23 ) . The majority of patients had papillary growth as a major component ( n = 14 ) . For 34 evaluable patients , median PFS , overall survival , and objective response rate ( ORR ) were 11.0 months , 18.5 months , and 29 % , respectively . PFS varied by histology ( P < .001 ) , and ORR was higher in patients with significant papillary ( seven of 18 ) or chromophobe ( two of five ) elements than for others ( one of 11 ) . Presence of papillary features were associated with benefit , including uRCC , where it correlated with ORR ( 43 % v 11 % ) , median PFS ( 12.9 v 1.9 months ) , and overall survival ( 28.2 v 9.3 months ; P < .001 ) . Several genetic alterations seemed to segregate by histology . In particular , somatic mutations in ARID1A were seen in five of 14 patients with papillary features but not in other RCC variants . All five patients achieved treatment benefit . Conclusion The study suggests efficacy for this combination in patients with ncRCC characterized by papillary features . Distinct mutational profiles among ncRCCs vary according to specific histology OBJECTIVES Primarily to evaluate the toxicity and , secondarily , the tumor response and patient survival associated with a three-phase combined modality treatment plan for patients with invasive transitional cell carcinoma ( TCC ) of the bladder ( T2-T4,NX-N2 , MO ) who are medically unsuitable for or who refuse cystectomy . METHODS Eligible patients initially underwent extensive transurethral resection ( TUR ) of the primary tumor with the attempt to resect disease totally . Subsequently , they received systemic combination chemotherapy consisting of two cycles of methotrexate , cisplatin , and vinblastine ( MCV ) , followed by cystoscopic re-evaluation of the bladder tumor . Patients then received 6480 cGy radiotherapy to the bladder with concurrent systemic cisplatin .  Toxicity , primary tumor response , and overall survival were evaluated . RESULTS Of 34 eligible patients , 27 patients completed the treatment series . Twenty-two received 80 % to 100 % of the prescribed doses of MCV and only 2 patients experienced grade 4 hematologic toxicities . The most common toxicities were gastrointestinal ( 23 ) , hematologic ( 21 ) , and renal ( 8) . The complete response ( CR ) rate after all treatment phases was 56 % ( 19 of 34 ) , 10 patients achieving a complete tumor resection of visible tumor at the initial TUR of the bladder ( TURB ) ; 3 , a CR after MCV ; and 6 , after radiotherapy and concomitant cisplatin . The median overall survival was 21 months with 6 of 34 ( 18 % ) alive at 57 months ( range , 36 to 75 ) . Complete resection of tumor by TURB was associated with prolonged overall survival . The bladder was the initial site of recurrence in 85 % of patients who had achieved a CR status . CONCLUSIONS This older age patient group tolerated this combined modality therapy with acceptable toxicities , but the overall survival rate was not improved compared with those reported with radiotherapy alone PURPOSE To integrate stage , grade , and Eastern Cooperative Oncology Group ( ECOG ) performance status ( PS ) into a clinical ly useful tool capable of stratifying the survival of renal cell carcinoma ( RCC ) patients . PATIENTS AND METHODS The medical records of 661 patients undergoing nephrectomy at University of California Los Angeles between 1989 and 1999 were evaluated . Median age was 61 years , male-to-female ratio was 2.2:1 , and median follow-up was 37 months .  Survival time was the primary end point assessed . Sixty-four possible combinations of stage , grade , and ECOG PS were analyzed and collapsed into distinct groups . The internal validity of the categorized was challenged by a univariate analysis and a multivariate analysis testing for the accountability of each UCLA Integrated Staging System ( UISS ) category against independent variables shown to have impact on survival . RESULTS Combining and stratifying 1997 tumor-node-metastasis stage , Fuhrman 's grade and ECOG PS result ed in five survival stratification groups design ated UISS , and numbered I to V. The projected 2- and 5-year survival for the UISS groups are as follows for the groups : I , 96 % and 94 % ; II , 89 % and 67 % ; III , 66 % and 39 % ; IV , 42 % and 23 % ; and V , 9 % and 0 % , respectively . UISS accounted for the significant variables in the variate analysis . CONCLUSION A novel system for staging and predicting survival for RCC integrating clinical variables is offered . UISS is simple to use and is superior to stage alone in differentiating patients ' survival . Our data suggests that UISS is an important prognostic tool for counseling patients with various stages of kidney cancer . Further prospect i ve large-scale validation with external data is awaited Objective . To evaluate the efficacy of autologous cytokine-induced killer ( CIK ) cells in patients with renal cell carcinoma ( RCC ) . Methods . 20 patients diagnosed with TNM stage I or II RCC were r and omly divided into two groups , a CIK cell treatment group and a control group . The endpoint was progression-free survival ( PFS ) evaluated by Kaplan-Meier analyses . Results . CD3 + , CD3+/CD8 + , CD3+/CD4 + , and CD3+/CD56 + levels increased after CIK cell culture ( P < 0.01 ) . The median PFS in CIK cell treatment group was significantly longer than that in control group ( PFS , 32.2 months versus 21.6 months ; log-rank , P = 0.032 ) , all patients were alive during the course of followup , and there are no statistically significant differences between two groups in OS ( log-rank , P = 0.214 ) . Grade III or greater adverse events were not observed . Conclusions . CIK cells treatment could prolong survival in patients with RCC after radical nephrectomy and showed acceptable curative effect with potential enhancement of cellular immune function . This trial is registered with Clinical trials.gov NCT01799083 BACKGROUND Sunitinib is a st and ard-of-care treatment in advanced clear cell renal cell carcinoma ( ccRCC ) . Retrospective and exp and ed access data suggest sunitinib has activity in advanced non-clear cell renal cell carcinoma ( nccRCC ) . OBJECTIVE To prospect ively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC . DESIGN , SETTING , AND PARTICIPANTS This is a single-arm phase 2 trial with a two-stage design . Eligibility criteria included pathologically confirmed nccRCC or ccRCC with ≥ 20 % sarcomatoid histology , performance status 0 - 2 , measurable disease , a maximum of two prior systemic therapies , and no prior treatment with tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptors . INTERVENTION Patients received sunitinib 50 mg daily on a 4-wk on , 2-wk off schedule . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary end points were objective response rate ( ORR ) and progression-free survival ( PFS ) . Secondary end points were safety and overall survival ( OS ) . RESULTS AND LIMITATIONS Fifty-seven patients were eligible ( nccRCC histology : papillary , 27 ; chromophobe , 5 ; unclassified , 8 ; collecting duct or medullary carcinoma , 6 ; sarcomatoid , 7 ; and others , 4 )  . Median PFS for 55 evaluable patients was 2.7 mo ( 95 % confidence interval [ CI ] , 1.4 - 5.4 ) . Two patients with chromophobe and one patient with unclassified histology had a confirmed partial response ( 5 % ORR ) . Median PFS for patients with papillary histology was 1.6 mo ( 95 % CI , 1.4 - 5.4 ) . Median PFS for patients with chromophobe histology was 12.7 mo ( 95 % CI , 8.5-NA ) . Median OS for all patients was 16.8 mo ( 95 % CI , 10.7 - 26.3 ) . Treatment-emergent adverse events were consistent with sunitinib 's mechanism of action . The nonr and omized design and small number of patients are limitations of this study . CONCLUSIONS The differential response of chromophobe histology to sunitinib suggests a therapeutically relevant biological heterogeneity exists within nccRCC . The low ORR and short PFS with sunitinib in the other nccRCC subtypes underscore the need to enroll patients with these diverse tumors in clinical trials Background Uro-oncological neoplasms have both a high incidence and mortality rate and are therefore a major public health problem . The aim of this study was to evaluate research activity in uro-oncology over the last decade . Methods We search ed MEDLINE and Clinical Trials.gov systematic ally for studies on prostatic , urinary bladder , kidney , and testicular neoplasms . The increase in newly published reports per year was analyzed using linear regression . The results are presented with 95 % confidence intervals , and a p value < 0.05 was considered statistically significant . Results The number of new publications per year increased significantly for prostatic , kidney and urinary bladder neoplasms ( all < 0.0001 ) . We identified 1,885 r and omized  controlled trials ( RCTs ) ; also for RCTs , the number of newly published reports increased significantly for prostatic ( p = 0.001 ) and kidney cancer ( p = 0.005 ) , but not for bladder ( p = 0.09 ) or testicular ( p = 0.44 ) neoplasms . We identified 3,114 registered uro-oncological studies in Clinical Trials.gov . However , 85 % of these studies are focusing on prostatic ( 45 % ) and kidney neoplasms ( 40 % ) , whereas only 11 % were registered for bladder cancers . Conclusions While the number of publications on uro-oncologic research rises yearly for prostatic and kidney neoplasms , urothelial carcinomas of the bladder seem to be neglected despite their important clinical role . Clinical research on neoplasms of the urothelial bladder must be explicitly addressed and supported Cytokine induced killer ( CIK ) cell-based treatments have shown antitumor activity against renal cell carcinoma ( RCC ) in vitro and in vivo . But the therapeutic options and benefits of various CIK cells were unknown for different stages of RCC . In this r and om clinical trial , the 3-year disease free survival ( DFS ) of operable RCC patients treated with autologous tumor lysate-pulsed dendritic cells co-cultured with cytokine induced killer ( Ag-DC-CIK ) was 96.7 % compared with 57.7 % in the control group . Ag-DC-CIK immunotherapy decreased the risk of post-operative disease progression and relapse ( P = 0.0418 ) . In inoperable RCC patients treated with CIK  , the 3-year overall survival ( OS ) and progression-free survival ( PFS ) were significantly longer than the control group ( P = 0.0116 and P = 0.0212 ) . The CD4(+)/CD8(+ ) T cell ratio in peripheral blood increased after the last cell infusion in the CIK treatment group , and especially further increased in the Ag-DC-CIK treatment group ( P = 0.002 ) . No severe toxicity was observed after infusion of CIK cells . Therefore , tumor antigen-sensitized Ag-DC-CIK cells might be more efficient and personalized for the patients with tumor resection , and CIK cells could improve the prognosis for those inoperable patients . According to the stages of RCC patients , different CIK cell-based immunotherapies would help to achieve more beneficial effects PURPOSE To compare the efficacy and local toxicity of the intravesical instillation of a cytostatic drug versus the same cytostatic agent in combination with local hyperthermia as an adjuvant treatment , after complete transurethral resection ( TURB ) of superficial transitional cell carcinoma ( TCC ) of the bladder . PATIENTS AND METHODS The study was design ed as a prospect i ve , multicentric , r and omized trial . Eighty-three patients suffering from primary or recurrent superficial ( Ta-T1 ) TCC of the bladder , after a complete TURB , were r and omly assigned to receive intravesical instillations of mitomycin C ( MMC ) alone , for 41 patients , and MMC in combination with local microwave-induced hyperthermia , for 42 patients . For the combined approach , a new system , Synergo101 - 1 ( Medical Enterprises , Amsterdam , the Netherl and s ) was used . The effectiveness evaluation end points of the study were evaluation of recurrence-free survival and the estimated probability of recurrence . The safety evaluation end points included subjective and objective side effects and clinical complications . For the efficacy end point , Kaplan-Meier analysis was employed , with the log-rank test for significance . Minimum follow-up time was 24 months . RESULTS Of the 83 r and omly assigned patients , 75 completed the study according to the protocol and had valid cystoscopy results . Survival analysis of the 75 assessable patients demonstrated a highly significant difference in the survival curves in favor of thermochemotherapy . Subjective intolerance and clinical complications were significantly higher but transient and moderate in the combined treatment group . CONCLUSION In our series , endovesical thermochemotherapy appears to be more effective than st and ard endovesical chemotherapy as an adjuvant treatment for superficial bladder tumors at 24-month follow-up , despite an increased but acceptable local toxicity PURPOSE To assess the effectiveness of two approaches of organ-sparing treatment in patients with invasive transitional cell bladder carcinoma . PATIENTS AND METHODS During the period from June 1996 to June 2000 , 33 patients with invasive transitional cell carcinoma ( T2 - 4 ) of the bladder were treated . Patients were divided into two groups . Group A included 17 patients treated with CMV systemic chemotherapy ( methotrexate 30 mg/m(2 ) and vinblastine 3 mg/m(2 ) , day 1 ; and cisplatin 70 mg/ m(2 ) , day 2 ) repeated every 3 weeks for 3 courses , combined with intravesical BCG . Complete responders ( CR ) received maintenance intravesical BCG , while partial responders ( PR ) were subjected to transurethral bladder resection ( TURB ) or partial bladder resection . Group B included 16 patients treated with maximal TURB followed by 2 CMV courses and radiotherapy . RESULTS Group A patients have been followed-up for a period of 7 to 48 months ( median 21.6 months ) . After completing the 2nd chemotherapy course , 2 patients refused further treatment and were excluded from the group . On completing chemoimmunotherapy 11 ( 73 % ) patients showed objective response ( CR+PR ) and preservation of the bladder was achieved . Four ( 27 % ) patients were treatment failures . Group B patients have been followed for a period of 9 to 47 months ( median 27.5 months ) . On completing treatment 12 of 16 ( 75 % ) patients showed an objective response with preservation of the bladder . Treatment failure was diagnosed in 4 ( 25 % ) patients . The 2 groups differed significantly in terms of side-effects , which were more pronounced in Group B patients . Of the late complications in Group B a serious problem was the development of severe radiation-induced fibrosis leading to microcystis and a cystectomy was indispensable in one of the patients . CONCLUSION The applied 2 approaches of combined organ-sparing treatment of invasive bladder carcinoma seem equally effective . Future r and omized studies are needed to define reliable criteria for patient selection BACKGROUND We investigated the efficacy of everolimus against nonclear-cell renal cell carcinoma ( nccRCC ) . Patients and methods Patients with nccRCC received 10-mg everolimus once daily until disease progression or unacceptable toxicity . PATIENTS who had received a VEGF- tyrosine kinase inhibitor ( TKI ) previously were included . RESULTS A total of 49 patients were enrolled . Twenty-three patients ( 46.9 % ) received prior anti-VEGF agents . A partial response was observed in five patients ( 10.2 % ) and stable disease in 25 patients ( 51.0 % ) . The disease progressed in 16 patients ( 32.7 % ) despite the administration of everolimus . Two of the five patients who showed an objective response to everolimus had chromophobe carcinoma , whereas two had papillary carcinoma and one had unclassifiable carcinoma . Thirty-six patients experienced disease progression during follow-up , and the median progression-free survival ( PFS ) was 5.2 months . Chromophobe RCC patients seemed to have longer PFS than nccRCC patients with the other histological subtypes ( P = 0.084 ) . Previous VEGF-TKI treatment did not influence the efficacy of everolimus , and the toxicity profiles were in line with previous reports . CONCLUSION Everolimus shows certain efficacy against nccRCC , particularly in patients with chromophobe RCC , and prior treatment with a VEGF-TKI appears not influencing the outcome of everolimus therapy in nccRCC patients . Clinical Trials.gov number NCT00830895 BACKGROUND Most early stage kidney cancers are renal cell carcinomas ( RCCs ) , and most are diagnosed incidentally by imaging as small renal masses ( SRMs ) . Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize . OBJECTIVE To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and /or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression . INTERVENTION Patients underwent serial imaging and needle core biopsies . MEASUREMENTS We measured rates of change in tumor diameter ( growth measured by imaging ) and progression to ≥ 4 cm , doubling of tumor volume , or metastasis with histology on biopsy . RESULTS AND LIMITATIONS Local progression occurred in 25 patients ( 12 % ) , plus 2 progressed with metastases ( 1.1 % ) . Of the 178 subjects with 209 SRMs , 127 with 151 SRMs had>12 mo of follow-up with two or more images , with a mean follow-up of 28 mo . Their tumor diameters increased by an average of 0.13 cm/yr . Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate . Limitations included no central review of imaging and pathology and a short follow-up . CONCLUSIONS This is the first SRM active surveillance study to correlate growth with histology prospect ively . In the first 2 yr , the rate of local progression to higher stage is low , and metastases are rare . SRMs appear to grow very slowly , even if biopsy proven to be RCC . Many patients with SRMs can therefore be initially managed conservatively with serial imaging , avoiding the morbidity of surgical or ablative treatment Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospect i ve bladder-preserving program consisting of  transurethral tumor resection , neoadjuvant chemotherapy ( methotrexate , cisplatin , and vinblastine [ MCV ] ) , and 4,000 cGy radiotherapy with concurrent cisplatin .  Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received  full-dose radiotherapy ( 6,480 cGy ) with cisplatin . Cystectomy was recommended to patients with residual disease . Distant metastasis rate was associated with tumor stage and size : 0 % in T2 patients , 39 % in T3 - 4 patients ( P = .035 ) , 6 % for tumors less than 5 cm , and 59 % for tumors greater than or equal to 5 cm ( P = .002 ) . Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ ( CIS ; 40 % ) than those without CIS ( 6 % ; P = .075 ) . Papillary tumors and solid tumors both had similar treatment outcomes . By multivariate analysis , tumor stage T2 ( P = .04 ) and absence of CIS ( P = .03 ) were significant predictors of complete response ; CIS was predictive of local bladder recurrence ( P = .07 ) ; and tumor size ( P = .03 ) , response after chemoradiotherapy ( P = .02 ) , and vascular invasion ( P = .08 ) were associated with distant metastasis . Six of eight local bladder tumor recurrences were superficial tumors . The low actuarial distant metastasis rate of T2 patients ( 0 % at 3 years ) , the 3-year actuarial overall survival rates for T2 ( 89 % ) and T3 - 4 ( 50 % ) patients , and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls . These results provide preliminary evidence ( median follow-up , 30 months ) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma . The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing r and omized trials
EVIDENCE SYNTHESIS The systematic review showed an absence of evidence for treating RKCs , with data only supporting sunitinib or MET inhibitors for some specific subtypes .
PATIENT SUMMARY Patients confronted with rare kidney cancers are often treated the same way as clear-cell renal cell carcinoma patients , despite little evidence from r and omized trials .
Molecular characterization of tumors to stratify patients may improve outcomes .
CONTEXT The European Association of Urology Renal Cell Carcinoma Guideline Panel recently conducted a systematic review of treatment options for patients with advanced non-clear-cell renal cell carcinomas ( RCCs ) , which showed a substantial lack of evidence for management recommendations .
OBJECTIVE To improve the outcomes of patients with rare kidney cancers ( RKCs ) , we performed a subsequent unstructured review to determine current treatment strategies and druggable pathways , involving key stakeholders with a global perspective to generate recommendations .