Jean-Christophe Bernhard

Magnetic Resonance Imaging–Transectal Ultrasound Image-fusion Biopsies Accurately Characterize the Index Tumor: Correlation with Step-sectioned Radical Prostatectomy Specimens in 135 Patients

BACKGROUND Prostate biopsies targeted by elastic fusion of magnetic resonance (MR) and three-dimensional (3D) transrectal ultrasound (TRUS) images may allow accurate identification of the index tumor (IT), defined as the lesion with the highest Gleason score or the largest volume or extraprostatic extension. OBJECTIVE To determine the accuracy of MR-TRUS image-fusion biopsy in characterizing ITs, as confirmed by correlation with step-sectioned radical prostatectomy (RP) specimens. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 135 consecutive patients who sequentially underwent pre-biopsy MR, MR-TRUS image-fusion biopsy, and robotic RP at two centers between January 2010 and September 2013. INTERVENTION Image-guided biopsies of MR-suspected IT lesions were performed with tracking via real-time 3D TRUS. The largest geographically distinct cancer focus (IT lesion) was independently registered on step-sectioned RP specimens. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS A validated schema comprising 27 regions of interest was used to identify the IT center location on MR images and in RP specimens, as well as the location of the midpoint of the biopsy trajectory, and variables were correlated. RESULTS AND LIMITATIONS The concordance between IT location on biopsy and RP specimens was 95% (128/135). The coefficient for correlation between IT volume on MRI and histology was r=0.663 (p<0.001). The maximum cancer core length on biopsy was weakly correlated with RP tumor volume (r=0.466, p<0.001). The concordance of primary Gleason pattern between targeted biopsy and RP specimens was 90% (115/128; κ=0.76). The study limitations include retrospective evaluation of a selected patient population, which limits the generalizability of the results. CONCLUSION Use of MR-TRUS image fusion to guide prostate biopsies reliably identified the location and primary Gleason pattern of the IT lesion in >90% of patients, but showed limited ability to predict cancer volume, as confirmed by step-sectioned RP specimens. PATIENT SUMMARY Biopsies targeted using magnetic resonance images combined with real-time three-dimensional transrectal ultrasound allowed us to reliably identify the spatial location of the most important tumor in prostate cancer and characterize its aggressiveness.

Update on the Medical Treatment of Metastatic Renal Cell Carcinoma

CONTEXT Metastatic renal cell carcinoma (mRCC) has long been treated only by immunotherapy with good results only in a small population of patients. In recent years, major improvements in treatment possibilities have occurred with the advent of anti-angiogenic drugs. In the past 2 yr, pivotal phase III trials have confirmed this major breakthrough by increasing the progression-free survival rates and/or overall survival rates provided by sunitinib, sorafenib, and bevacizumab, and more recently by the mTOR (mammalian target of rapamycin) inhibitors temsirolimus and everolimus. OBJECTIVE To update the previous review on smart drugs published in the European Journal in 2006 (Patard JJ, et al. Understanding the importance of smart drugs in renal cell carcinoma. Eur Urol 2006; 49:633-43). EVIDENCE ACQUISITION Critical review of published literature 2006-2008 (Pubmed website search words: renal cell carcinoma and/or targeted therapy and prospective trials) and more recent meeting abstracts (American Society of Clinical Oncology 2007). Quality assessment included prospective phase I-III trials and critical evaluations with low numbers of patients, retrospective analyses, and slide presentations of meeting abstracts. EVIDENCE SYNTHESIS This review presents the current situation and provides more recent data on sequential treatment, the association of targeted drugs, and the treatment of non-clear-cell histologies. CONCLUSIONS Treatment of mRCC with targeted therapy centers on at least two major pathways: angiogenesis and mTOR involving inhibiting drugs that may be used alone, in combination, or sequentially.

Renal Cell Carcinoma (RCC) in Patients With End-Stage Renal Disease Exhibits Many Favourable Clinical, Pathologic, and Outcome Features Compared With RCC in the General Population

BACKGROUND Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. OBJECTIVE Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. DESIGN, SETTING, AND PARTICIPANTS Twenty-four French university departments of urology participated in this retrospective study. INTERVENTION All patients were treated according to current European Association of Urology guidelines. MEASUREMENTS Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥ 3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. CONCLUSIONS RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.

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.

Predictive Value of Magnetic Resonance Imaging Determined Tumor Contact Length for Extracapsular Extension of Prostate Cancer

PURPOSE Tumor contact length is defined as the amount of prostate cancer in contact with the prostatic capsule. We evaluated the ability of magnetic resonance imaging determined tumor contact length to predict microscopic extracapsular extension compared to existing predictors of extracapsular extension. MATERIALS AND METHODS We retrospectively analyzed the records of 111 consecutive patients with magnetic resonance imaging/ultrasound fusion targeted, biopsy proven prostate cancer who underwent radical prostatectomy from January 2010 to July 2013. Median patient age was 64 years and median prostate specific antigen was 8.9 ng/ml. Clinical stage was cT1 in 93 cases (84%) and cT2 in 18 (16%). Postoperative pathological analysis confirmed pT2 in 71 patients (64%) and pT3 in 40 (36%). We evaluated 1) in the radical prostatectomy specimen the correlation of microscopic extracapsular extension with pathological cancer volume, pathological tumor contact length and Gleason score, 2) the correlation between microscopic extracapsular extension and magnetic resonance imaging tumor contact length, and 3) the ability of preoperative variables to predict microscopic extracapsular extension. RESULTS Logistic regression analysis revealed that pathological tumor contact length correlated better with microscopic extracapsular extension than the predictive power of pathological cancer volume (0.821 vs 0.685). The Spearman correlation between pathological and magnetic resonance imaging tumor contact length was r = 0.839 (p <0.0001). ROC AUC analysis revealed that magnetic resonance imaging tumor contact length outperformed cancer core involvement on targeted biopsy and the Partin tables to predict microscopic extracapsular extension (0.88 vs 0.70 and 0.63, respectively). At a magnetic resonance imaging tumor contact length threshold of 20 mm the accuracy for diagnosing microscopic extracapsular extension was superior to that of conventional magnetic resonance imaging criteria (82% vs 67%, p = 0.015). We developed a predicted probability plot curve of extracapsular extension according to magnetic resonance imaging tumor contact length. CONCLUSIONS Magnetic resonance imaging determined tumor contact length could be a promising quantitative predictor of microscopic extracapsular extension.

Cancer-specific and non-cancer-related mortality rates in European patients with T1a and T1b renal cell carcinoma

To examine cancer‐specific and non‐cancer‐related mortality rates in 451 patients with T1a–bN0M0 renal cell carcinoma (RCC) treated with either radical or partial nephrectomy (RN or PN) in Europe.

Early unclamping technique during robot-assisted laparoscopic partial nephrectomy can minimise warm ischaemia without increasing morbidity.

To compare perioperative outcomes of early unclamping (EUC) vs standard unclamping (SUC) during robot‐assisted partial nephrectomy (RAPN), as early unclamping of the renal pedicle has been reported to decrease warm ischaemia time (WIT) during laparoscopic PN.

Therapeutic Management of De Novo Urological Malignancy in Renal Transplant Recipients: The Experience of the French Department of Urology and Kidney Transplantation from Bordeaux

OBJECTIVES To determine and analyze the incidence, prognosis, and therapeutic strategy of de novo urological malignancies in a series of renal transplant recipients (RTRs). METHODS A retrospective study of 1350 recipients between January 1998 and January 2008 was carried out; we reviewed the data of 42 de novo urological malignancies in 39 recipients. RESULTS There were 21 cases of prostate cancer, 13 cases of renal cell carcinoma in 10 patients, 3 cases of renal graft tumors, and 5 cases of transitional cell carcinoma of the bladder. The overall incidence of urological neoplasms was 3.1%. The mean age of cancer diagnosis was 60 +/- 8.3 years. The mean duration of dialysis before cancer diagnosis was 35 +/- 37.5 months. About 92% of patients underwent hemodialysis (34/39) and the remaining underwent peritoneal dialysis (5/39). All the 39 recipients received cadaveric kidneys. The mean follow-up period for this study was 33 +/- 34.4 months (range 2-160 months). There appears to be a greater risk of urological neoplasm in RTRs. Prostate cancer and renal carcinoma can be treated in a similar manner than in general population with encouraging oncological results and low morbidity. However, the transitional cell carcinoma of the bladder remains particularly aggressive requiring optimal treatment despite the morbidity concerning the intravesical therapy. CONCLUSIONS We can apply the standard medical and surgical treatment in RTRs, with encouraging oncological results if a strict screening program is established and followed by the patients.

Predictive Factors for Ipsilateral Recurrence After Nephron-sparing Surgery in Renal Cell Carcinoma

BACKGROUND Ipsilateral recurrence after nephron-sparing surgery (NSS) is rare, and little is known about its specific determinants. OBJECTIVE To determine clinical or pathologic features associated with ipsilateral recurrence after NSS performed for renal cell carcinoma (RCC). DESIGN, SETTING, AND PARTICIPANTS We analysed 809 NSS procedures performed at eight academic institutions for sporadic RCCs retrospectively. MEASUREMENTS Age, gender, indication, tumour bilaterality, tumour size, tumour location, TNM stage, Fuhrman grade, histologic subtype, and presence of positive surgical margins (PSMs) were assessed as predictors for recurrence in univariate and multivariate analysis by using a Cox proportional hazards regression model. RESULTS AND LIMITATIONS Among 809 NSS procedures with a median follow-up of 27 (1-252) mo, 26 ipsilateral recurrences (3.2%) occurred at a median time of 27 (14.5-38.2) mo. In univariate analysis, the following variables were significantly associated with recurrence: pT3a stage (p=0.0489), imperative indication (p<0.01), tumour bilaterality (p<0.01), tumour size >4cm (p<0.01), Fuhrman grade III or IV (p=0.0185), and PSM (p<0.01). In multivariate analysis, tumour bilaterality, tumour size >4cm, and presence of PSM remained independent predictive factors for RCC ipsilateral recurrence. Hazard ratios (HR) were 6.31, 4.57, and 11.5 for tumour bilaterality, tumour size >4cm, and PSM status, respectively. The main limitations of this study included its retrospective nature and a short follow-up. CONCLUSIONS RCC ipsilateral recurrence risk after NSS is significantly associated with tumour size >4cm, tumour bilaterality (synchronous or asynchronous), and PSM. Careful follow-up should be advised in patients presenting with such characteristics.

Recommandations en onco- urologie 2013 du CCAFU : Cancer du rein

Resume Introduction L’objectif de ce travail a ete d’etablir par le sous-comite rein du CCAFU des recommandations pour le diagnostic, le bilan, les traitements et la prise en charge des tumeurs du rein. Methodes Le sous-comite a remis a jour les recommandations de 2010 en s’appuyant sur une revue exhaustive de la litterature effectuee sur PubMed, en evaluant les references et leur niveau de preuve. Resultats Le scanner renal multiphasique est le standard diagnostique pour les tumeurs renales. Les biopsies renales sont d’importance croissante dans la mesure ou elles peuvent modifier la prise en charge. La nephrectomie partielle est a envisager systematiquement pour les tumeurs cT1. La voie incisionnelle reste le standard pour les cancers du rein localement avances. Le traitement des cancers du rein metastatiques inclut de nouvelles drogues. Le role de la nephrectomie en situation metastatique reste a demontrer dans le cadre de l’essai Carmena. Conclusions Les therapies mini-invasives et conservatrices prennent une part croissante dans les cancers du rein localises. L’arsenal therapeutique continue a s’enrichir pour les formes metastatiques.