Christian Beisland

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

BACKGROUND Renal masses diagnosed in older and comorbid patients represent a challenge with regard to treatment. OBJECTIVE To evaluate clinical outcome and tumor progression in patients with renal masses managed by observation due to age and comorbidity. DESIGN, SETTING, AND PARTICIPANTS The medical records of 63 consecutive patients with renal masses primarily managed by observation during 2002-2007 were reviewed retrospectively and analyzed. The mean age for all patients at diagnosis was 76.6 yr, and 59% were male. Mean tumor size was 4.3 cm in diameter at diagnosis. Of these, 30% had Eastern Cooperative Oncology Group performance status (PS) of 2 or 3, 78% were American Society of Anesthesiologists (ASA) class 3, and the patients had a mean of 2.8 other medical conditions. MEASUREMENTS Registration of age, ASA class, PS, comorbid conditions, computed tomography scans, primary tumor size, tumor growth rate, pathology parameters, observation time, survival time. RESULTS AND LIMITATIONS Five-year overall survival (OS) and cancer-specific survival (CSS) rates were 42.8% and 93.3%, respectively. For tumors < or =4.0 cm in size, 5-yr CSS was 100%. Nine patients received delayed radical treatment, none of whom had later progression of the disease. In 18 patients histopathologic diagnosis of the renal masses were available, and in 15 patients (83%) renal cell carcinoma (RCC) was verified. The annual growth rate was <1cm/yr in 85.4% of the cases. In tumors < or =4.0 cm, only 1 of 27 tumors (3.7%) grew faster than 1cm/yr. CONCLUSIONS Management of renal masses by observation among older and comorbid patients seems to give acceptable results with regard to OS and CSS rates after 5 yr. The risk of disease progression is significantly higher in patients with larger sized renal masses (>4 cm). Thus, selection for observation in this group has to be stricter than in a group of patients with smaller sized renal masses (< or =4.0 cm).

Multiple primary malignancies in patients with renal cell carcinoma: a national population-based cohort study.

To determine the possibly greater occurrence of multiple malignancies in patients with renal cell carcinoma (RCC).

Renal Cell Carcinoma: Gender Difference in Incidental Detection and Cancer-specific Survival

Objective : To look for an increase in the incidental detection of renal cell carcinoma (RCC) over the last two decades and to see if different patterns of healthcare use for men and women have implications for tumour detection and survival. Material and Methods : We present an historical series of 368 consecutive patients treated with nephrectomy for RCC during the period 1978-2000. The patients were classified according to detection mode (incidental or symptomatic disease), TNM stage and cancer-related death. Results : The frequency of incidentally detected RCC (IRCC) increased from 21.1% to 34.7% between the first and second decades of the study. The IRCC group had significantly more low-stage (I-II) tumours ( p = 0.002), a smaller tumour size ( p < 0.0001) at operation and significantly better cancer-specific survival ( p = 0.0048) than the symptomatic renal cell carcinoma (SRCC) group. The frequency of women was significantly higher in the IRCC group than in the SRCC group ( p = 0.02). Females had significantly more low-stage (I-II) tumours ( p = 0.02) and better cancer-specific survival ( p = 0.05) than males. Conclusions : The number of incidentally discovered renal tumours is increasing. IRCC have lower TNM-stage and are smaller than SRCC. IRCC have better long term cancer specific survival than SRCC. The better survival rate found in females may be due to more extensive use of the healthcare system by females than males.

Nephrectomy – Indications, Complications and Postoperative Mortality in 646 Consecutive Patients

Objective: To gain information about the indications for and complications of conventional nephrectomy, also to create standards for future evaluation of nephrectomies performed by minimal invasive techniques.Methods: We present a historical 20 years’ series of 646 consecutive nephrectomies performed in the period of 1978–1997. Malignant disease led to the operation in 437 cases, of which 98 were urothelial tumors in the renal pelvis or ureter. 209 kidneys were removed due to benign conditions. The incidence of nephrectomy for benign conditions has declined from 75 in the first 5–year period to 32 in the last.Results and Discussion: Postoperative complications occurred in 100 patients (15.5%). Nephrectomy for malignant disease had a significantly higher rate of complications than operations for benign conditions (p<0.001), especially hemorrhagic complications and pneumonias were more frequent. There were no differences as a result of the operative approach. Reoperation was carried out in 3.0% of the cases. Overall mortality rate (<30 days) was 3.1%.

Obesity is associated with an improved cancer-specific survival, but an increased rate of postoperative complications after surgery for renal cell carcinoma.

Abstract Objective. This study aimed to assess the impact of preoperative body mass index (BMI) on postoperative complications, cancer-specific survival (CSS) and overall survival (OS) in patients operated for renal cell carcinoma (RCC). Material and methods. The study included 397 patients with BMI values, who underwent surgery for RCC between 1 January 1997 and 31 December 2010. Obese patients (BMI > 30 kg/m2) were compared to non-obese patients (BMI < 30 kg/m2) in regard to CSS and OS. A Cox proportional hazard model was used for the multivariate survival analyses. The mean age of the patients was 62.1 years. There were 259 males (65%) and 325 patients (82%) were non-obese. Mean BMI was 26 kg/m2. Results. In the total material, CSS was 94.7% for obese patients and 74.8% for non-obese patients (p = 0.06). The obese group had significantly better CSS in univariate analysis for presumed radically treated disease (pT1–3N0M0). Obesity was a significant protective prognostic factor in multivariate analysis. An accelerating protective effect for CSS was found with increasing levels of BMI. In regard to OS, no difference was found between the two groups. Obese patients had a significantly lower age, and a higher rate of diabetes mellitus, hypertension and incidental detection. Obese patients had a significantly higher total incidence of postoperative complications, but not surgery-related complications. Conclusions. In this material, increasing BMI was associated with improved CSS for presumed radically treated patients. However, obese patients had a higher total rate of postoperative complications.

1.5-T multiparametric MRI using PI-RADS: a region by region analysis to localize the index-tumor of prostate cancer in patients undergoing prostatectomy

Background The use of multiparametric magnetic resonance imaging (mpMRI) to detect and localize prostate cancer has increased in recent years. In 2010, the European Society of Urogenital Radiology (ESUR) published guidelines for mpMRI and introduced the Prostate Imaging Reporting and Data System (PI-RADS) for scoring the different parameters. Purpose To evaluate the reliability and diagnostic performance of endorectal 1.5-T mpMRI using the PI-RADS to localize the index tumor of prostate cancer in patients undergoing prostatectomy. Material and Methods This institutional review board IRB-approved, retrospective study included 63 patients (mean age, 60.7 years, median PSA, 8.0). Three observers read mpMRI parameters (T2W, DWI, and DCE) using the PI-RADS, which were compared with the results from whole-mount histopathology that analyzed 27 regions of interest. Inter-observer agreement was calculated as well as sensitivity, specificity, positive predictive value (PPV), and negative predicted value (NPV) by dichotomizing the PI-RADS criteria scores ≥3. A receiver-operating curve (ROC) analysis was performed for the different MR parameters and overall score. Results Inter-observer agreement on the overall score was 0.41. The overall score in the peripheral zone achieved sensitivities of 0.41, 0.60, and 0.55 with an NPV of 0.80, 0.84, and 0.83, and in the transitional zone, sensitivities of 0.26, 0.15, and 0.19 with an NPV of 0.92, 0.91, and 0.92 for Observers 1, 2, and 3, respectively. The ROC analysis showed a significantly increased area under the curve (AUC) for the overall score when compared to T2W alone for two of the three observers. Conclusion 1.5 T mpMRI using the PI-RADS to localize the index tumor achieved moderate reliability and diagnostic performance.

Transcriptome Sequencing (RNAseq) Enables Utilization of Formalin-Fixed, Paraffin-Embedded Biopsies with Clear Cell Renal Cell Carcinoma for Exploration of Disease Biology and Biomarker Development.

Formalin-fixed, paraffin-embedded (FFPE) tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater® (Qiagen, Germany) stored samples from clear cell renal cell carcinoma (ccRCC) patients to investigate feasibility of RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater®. RNA sequencing libraries were generated applying the new Illumina TruSeq® Access library preparation protocol. Comparative analysis was done using voom/Limma R-package. The analysis of the FFPE and RNAlater® datasets yielded similar numbers of detected genes, differentially expressed transcripts and affected pathways. The FFPE and RNAlater datasets shared 80% (n = 1106) differentially expressed genes. The average expression and the log2 fold changes of these transcripts correlated with R2 = 0.97, and R2 = 0.96, respectively. Among transcripts with the highest fold changes in both datasets were carbonic anhydrase 9 (CA9), neuronal pentraxin-2 (NPTX2) and uromodulin (UMOD) that were confirmed by immunohistochemistry. IPA revealed the presence of gene signatures of cancer and nephrotoxicity, renal damage and immune response. To simulate the feasibility of clinical biomarker studies with FFPE samples, a classifier model was developed for the FFPE dataset: expression data for CA9 alone had an accuracy, specificity and sensitivity of 94%, respectively, and achieved similar performance in the RNAlater dataset. Transforming growth factor-ß1 (TGFB1)-regulated genes, epithelial to mesenchymal transition (EMT) and NOTCH signaling cascade may support novel therapeutic strategies. In conclusion, in this proof of concept study, RNAseq data obtained from FFPE kidney biopsies are comparable to data obtained from fresh stored material, thereby expanding the utility of archival tissue specimens.

Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma

BACKGROUND Cytoreductive nephrectomy has been the standard of care in metastatic renal‐cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal‐cell carcinoma who were receiving targeted therapies. METHODS In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with confirmed metastatic clear‐cell renal‐cell carcinoma at presentation who were suitable candidates for nephrectomy to undergo nephrectomy and then receive sunitinib (standard therapy) or to receive sunitinib alone. Randomization was stratified according to prognostic risk (intermediate or poor) in the Memorial Sloan Kettering Cancer Center prognostic model. Patients received sunitinib at a dose of 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The primary end point was overall survival. RESULTS A total of 450 patients were enrolled from September 2009 to September 2017. At this planned interim analysis, the median follow‐up was 50.9 months, with 326 deaths observed. The results in the sunitinib‐alone group were noninferior to those in the nephrectomy–sunitinib group with regard to overall survival (stratified hazard ratio for death, 0.89; 95% confidence interval, 0.71 to 1.10; upper boundary of the 95% confidence interval for noninferiority, ≤1.20). The median overall survival was 18.4 months in the sunitinib‐alone group and 13.9 months in the nephrectomy–sunitinib group. No significant differences in response rate or progression‐free survival were observed. Adverse events were as anticipated in each group. CONCLUSIONS Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal‐cell carcinoma who were classified as having intermediate‐risk or poor‐risk disease. (Funded by Assistance Publique–Hôpitaux de Paris and others; CARMENA ClinicalTrials.gov number, NCT00930033.)

Presumed radically treated renal cell carcinoma: Recurrence of the disease and prognostic factors for subsequent survival

Objective: To gain knowledge about when, where and how metastases after presumed radical treatment for renal cell carcinoma (RCC) are detected, and to use this information to establish a follow‐up programme for radically treated RCC. Further aims were to establish survival rates, together with identifying prognostic factors influencing survival for different groups of patients after recurrence of the disease. Material and Methods: A retrospective study of 305 pT1‐4N0M0/pT1‐4NxM0 (clinically N0) tumours treated with nephrectomy was performed. Results: A total of 89 patients (29.2%) developed metastases, with a median time to recurrence of 25.1 months. Within 5 years, 80% of the metastases had been detected. The lungs were the commonest metastatic site. A total of 34.8% of the recurrences were diagnosed as a result of routine follow‐up. Median cancer‐specific survival (CSS) after recurrence was 9.8 months. For patients with a disease‐free interval (DFI) ≥24 months the median CSS was 35 months. In a univariate analysis, performance status, DFI ≥24 months, metastases in a single organ, primary tumour size ≤70 mm, primary tumour stage pT1‐2 and age <65 years were all associated with better survival. In a multivariate analysis, performance status, DFI and number of organs affected were independent predictors of survival. Conclusion: The information from this material is used to suggest a simple, but adequate, follow‐up protocol. Easily accessible information can be used to identify groups with different prognoses regarding survival after recurrence of the disease.

Incidentally detected renal cell carcinomas are highly associated with comorbidity and mortality unrelated to renal cell carcinoma

Abstract Objective. The aim of this study was to investigate the underlying reasons for symptomatic (SRCC) and incidental diagnosis of renal cell carcinoma (IRCC), and possible differences in cancer-specific (CSS) and overall survival (OS) with regard to reasons for detection. Material and methods. Between 1997 and 2010, 413 patients underwent surgery for renal cell carcinoma (RCC). SRCCs were divided into groups with general and classical symptoms. IRCCs were divided into “true” IRCCs, found owing to investigation of another definitive medical condition, and “unrelated” IRCCs, found owing to investigation for signs and symptoms presumed to be unrelated to RCC. Gender- and age-adjusted estimated overall survival (EOS) rates based on national mortality data were calculated for both the total material and the subgroups. Results. IRCC tumours were smaller, and of lower stage and grade than SRCCs, which was also reflected in the lower CSS in this group. Most IRCCs were found during investigations related to another definitive condition. There was a significantly higher level of comorbidity in the IRCC group, and the “true” IRCC group had the highest rates. The two IRCC subgroups had similar CSS and tumour characteristics. In the SRCC group, however, those with general symptoms had worse tumour characteristics and lower rates of CSS compared to those with classical symptoms. The true IRCC group had significantly inferior OS compared to the unrelated IRCCs (p = 0,040). Only the unrelated IRCC patients had an OS similar to the EOS; for all other subgroups the OS was inferior to the EOS. Conclusions. Most IRCCs were found during investigations for other medical conditions, and the OS rate in this group of patients was lower than expected.