452 THE REPORTING QUALITY OF RANDOMISED CONTROLLED TRIALS IN UROLOGICAL SURGERY

449

CAIX level and VHL mutation do not improve the ability to predict renal cell carcinoma-specific mortality in patients treated with nephrectomy

Karakiewicz P.I.1, Trinh Q.D.1, Fregelot P.2, Hutterer G.C.1, Rioux N.3, Belldegrun A.S.4, Figlin R.A.4, Pantuck A.J.4, Patard J.J.2 University of Montreal Health Center, Cancer Prognostics and Health Outcomes Unit, Montreal, Canada, 2Rennes University Hospital, Urology, Rennes, France, 3Rennes University Hospital, Pathology, Rennes, France, 4David Geffen School of Medicine, University of California, Urology, Los Angeles, United States of America 1

Introduction & Objectives: CAIX expression and the presence of VHL mutation represent promising predictors of renal cell carcinoma-specific mortality (RCC-SM) in patients with sporadic renal cell carcinoma (RCC). We tested the ability of these two variables to predict RCC-SM in a prospectively recorded cohort of patients treated with nephrectomy. Material & Methods: Radical nephrectomy was performed in 100 patients at two centers. Genomic DNA was extracted using the QIAmp® DNA mini kit (Qiagen) from frozen tumor samples. Four amplimers covering the whole coding sequence and exon/intron junctions of the VHL gene were synthesized by PCR followed by Big Dye sequencing (Applied Biosystems). Mutation-bearing sequences were confirmed in a second round of PCR and sequencing reactions. Tumor CAIX expression was determined by immunohistochemistry. Life table, Kaplan-Meier and Cox regression analyses addressed RCC-SM. Covariates included age, gender, TNM stage, tumor size, Fuhrman grade and ECOG performance status. Results: The median survival of the cohort was 5.5 years. Genomic VHL mutations were identified in 58 patients (58%) and CAIX level ranged from 0 to 100. The most informative CAIX cut-off corresponded to a breakpoint situated at 0.85, similar to what has been previously described. Categorically-coded CAIX represented a statistically significant predictor of RCC-SM (p=0.002). Conversely, VHL mutation failed to show statistical significance, although a trend was observed for a poorer outcome when VHL was not mutated (p=0.08). In multivariable Cox regression analyses, neither CAIX (p=0.06) nor VHL (p=0.4) achieved independent predictor status, when adjustment was made for age, gender, TNM stage, tumor size, Fuhrman grade and ECOG performance status.

Renal follow-up of HLRCC syndrome patients

450

Kujala M.1, Aittomäki K.2, Ruutu M.3 Helsinki University Hospital, University of Helsinki and Päijät-Häme Central Hospital, Dep. of Urology, Dep. of Medical Genetics and Dep. of Surgery, Helsinki and Lahti, Finland, 2 Helsinki University Hospital, Dep. of Clinical Genetics, Helsinki, Finland, 3Helsinki University Hospital, Dep. of Urology, Helsinki, Finland 1

Introduction & Objectives: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a recently identified rare autosomal dominant tumor susceptibility syndrome caused by mutations in fumarate hydratase (fumarase, FH) gene. A subset of HLRCC families is prone to early-onset aggressive renal cell carcinoma of papillary type 2 or collecting duct histology. The natural course of HLRCC is poorly known so far. Early detection of presymptomatic tumors potentially improves the prognosis. However, it is not known how and when the patients with FH mutations should be screened for RCC. Material & Methods: We have collected the first clinical data on the HLRCC patients who have been followed up in Helsinki University Hospital for known risk of RCC. Altogether five patients (aged 21-51, mean 34.8), confirmed by DNA analyses to have FH mutation, and with family history of early-onset RCC, have attended regular clinical and radiological followup, to date for 1.5-14 years (mean 5.2). Ultrasound (US) of the abdomen has been used as the main imaging tool, complemented with CT-scan or MRI in case of any suspicious findings. The routine follow-up interval has been one year. Results: Four patients have not had any signs of RCC in their yearly imaging, but two have simple cysts. In the remaining patient, a 51 year old lady, a 2.4 cm tumor developed on the right kidney during the one year follow-up interval. The tumor was clearly visible in MRI. Due to the tumor location and suspicion of multifocality, radical nephrectomy was done. Histological examination revealed one tumor, a typical papillary RCC type 2, Fuhrman grade 3. On the remaining left kidney with two cysts, one cyst has changed in its appearance and a kidney resection will be done promptly.

Conclusions: Neither CAIX nor VHL mutation improve the ability to predict RCC-SM in patients treated with nephrectomy.

Conclusions: The natural course of RCC in hereditary forms of the disease is still poorly understood. Since these syndromes are rare, the number of patients at any given institution is small. Therefore it is essential that the clinical data is shared. US has turned out to be unreliable in detecting type 2 papillary RCC. CT is more sensitive but will expose an already cancer prone patient to a fairly large amount of radiation during a follow-up of several decades. Therefore, we have experienced contrast medium enhanced MRI to be a sensitive and safe method for screening these tumors. Since our case with a relatively large and highly malignant tumor developing in less than one year, we have now compressed the screening interval of HLRCC patients into 6 months and recommend contrast enhanced MRI as the primary imaging method.



O10 BPH: INTERVENTION THERAPY 1 Thursday, 22 March, 14.00-15.30, Room 2

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Long-term follow-up of 814 cases with non-metastatic renal cell carcinoma: definition of a surveillance protocol based on UCLA integrated staging system Antonelli A., Cozzoli A., Zani D., Zanotelli T., Cosciani Cunico S., Simeone C.

Introduction & Objectives: 20-40% of patients undergoing surgery for non-metastatic renal cancer experience disease recurrence during follow-up. The purpose of the study is to define a follow-up protocol based on UCLA Integrated Staging System (UISS) for patients undergoing surgery for N0M0 renal cancer. Material & Methods: The clinical records of patients treated with radical surgery for N0/Nx M0 renal cell carcinoma and monitored through periodic follow-up studies (at least 24 months in cases of diseasefree patients) were reviewed retrospectively out of 1,399 cases surgically treated for renal neoplasm between 1983 and 2005. Each case was assigned to a UISS risk category. Recurrence features, time and site were recorded. In particular, recurrence sites were categorized into local, renal (homolateral or controlateral) and distant. Results: The records of 814 patients with mean follow-up of 75.6 months were reviewed. UISS risk categories were distributed as follows: high risk (HR) 17.2%; intermediate risk (IR) 51.6%; low risk (LR) 31.2%. Disease-free survival rates at 5 years were 96.5%, 88.3% and 63.9% (log rank test p<0.0001) respectively. The disease recurred in 193 cases (23.7%) at distant sites (73.0% of recurrences), locally (11.9%), in the controlateral kidney (10.9%) and in the homolateral kidney (4.1%). A significant correlation was identified between UISS category and risk of recurrence (p<0.0001). In the first 5 years of follow up recurrence time and site distribution show that LR group has a mild risk of abdominal recurrence, with a prevalence of renal recurrence, and a very low risk of thoracic metastasis. Differently, IR and HR groups has a risk respectively higher to recur both in the abdomen, usually with distant or local relapses, or in the chest. In the following 5 years for LR patients there is a further reduction of the risk, whereas a lower but significant number of recurrences, mainly in the chest and less in the abdomen, persisted for IR and HR patients. After 10 years of follow-up, recurrences were extremely rare and almost exclusively located in the controlateral kidney. The table shows the follow up scheme suggested. 0-5 years Thoracic study every 30 months and abdominal study yearly

IR HR

Thoracic and abdominal study every 6 months

6-10 years Thoracic and abdominal study every 30 months Thoracic study yearly and abdominal study every 30 months Thoracic and abdominal study yearly

Muir G., Agha R. King’s College Hospital, Urology, London, United Kingdom

University of Brescia, Urology, Brescia, Italy

UISS class LR

452

The Reporting Quality of Randomised Controlled Trials in Urological Surgery

>10 years

Abdominal study every 5 years

Conclusions: In our experience non-metastatic renal neoplasms recur in approximately 25% of cases, mainly taking the form of distant metastases. We confirm the prognostic accuracy and repeatability of UCLA Integrated Staging System.

Introduction & Objectives: The CONSORT statement on randomised trials (RCT’s) is accepted by the leading biomedical journals as the minimum standard for reporting. To assess compliance with the CONSORT statement, and quantify trends and patterns of compliance, we examined the reporting quality of RCT’s, involving urological surgical techniques (as the intervention) published in the years 2000-2003.. Following our initial findings in urology, we extended the methodology to a number of other specialties to assess whether our findings in urology could be generalised to other surgical disciplines. Material & Methods: The Royal Society of Medicine (RSM) Library was commissioned to search the Medline and Cochrane databases for RCTs published in English. Additional analyses of five other specialties (non-urological trials: cardiovascular, gastrointestinal, hepatobiliary, orthopaedic and vascular) were also made: 15 English language trials (from each specialty) were randomly picked from a blast search conducted by the RSM for the year 2003. The RCTs were given a score out of 22, reflecting how many of the CONSORT items were complied with (with each item being given equal weighting), this score was termed the “CONSORT score”. Results: In total 122 RCT abstracts were identified which met the inclusion criteria for this study. From these, 32 were excluded as they were follow-up studies, involved a virtual procedure or were a cost analysis, leaving 90 RCTs (68.2%) published across 35 different journals which were analysed. The range of scores was 6-18 (mean 11.1). No trials reported how they implemented their randomisation process. Only 46% of RCTs stated that they had permission from an ethics review board. 20% had declared sources of funding, 14% stated whether there were any conflicts of interest and only 1.1% stated their trial registry number. For non-urological studies, an average CONSORT score of 11.2 was obtained. Conclusions: RCTs in Urology and other surgical disciplines demonstrate poor compliance with the CONSORT statement. We would recommend that urological and other surgical Journals consider supporting the CONSORT statement and have compliance ‘hard-wired’ into their submission, editorial and peer-review processes. Since it seems the best researchers are unable to produce RCT results which enable surgical techniques to be critically assessed, we feel an open debate is needed on the possible role of other research designs such as tracker studies.

Eur Urol Suppl 2007;6(2):135