Systemic therapy in metastatic renal cell carcinoma (mRCC): an evidence-based recommendation of the German interdisciplinary RCC guidelines group.

PURPOSE: The treatment landscape in metastatic renal cell carcinoma (mRCC) has evolved dramatically in recent years. Within the German guideline committee for RCC we evaluated current medical treatments and gave recommendations. METHODS: A systematic review of published evidence for medical treatment of mRCC was performed (July 2016-August 2019) to cover the duration from last guideline update in 2016. Evidence was graded according to SIGN ( http://www.sign.ac.uk/pdf/sign50.pdf ). Recommendations were made on the basis of a nominal group work with consensus approach and included patient advocates and shareholder of the German RCC treatment landscape. Each recommendation was graded according to its strength as strong recommendation (A) or recommendation (B). Expert statements were given, where appropriate. RESULTS: Strong first-line recommendations (IA) exist for axitinib + pembrolizumab (all risk categories) and ipilimumab + nivolumab (intermediate or poor risk only). Axitinib + avelumab is a recommended first-line treatment across patients with any risk category (IB). In patients who are not candidates for immune check point inhibitor (ICI) combinations, targeted agents should be offered as an alternative treatment. Subsequent treatment after ICI-based combinations remain ill-defined and no standard of care can be formulated. CONCLUSION: ICI-based combinations are the first-line standard of care and should be considered accordingly. There is an unmet medical need for pivotal studies that define novel standards in patients with failure of ICI-based combinations.

18F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing tyrosine kinase or checkpoint inhibitor therapy: preliminary results.

INTRODUCTION: Tyrosine kinase (TKI) and checkpoint inhibitors (CI) prolonged overall survival in metastatic renal cell carcinoma (mRCC). Early prediction of treatment response is highly desirable for the individualization of patient management and improvement of therapeutic outcome; however, serum biochemistry is unable to predict therapeutic efficacy. Therefore, we compared 18F-PSMA-1007 PET imaging for response assessment in mRCC patients undergoing TKI or CI therapy compared to CT-based response assessment as the current imaging reference standard. METHODS: 18F-PSMA-1007 PET/CT was performed in mRCC patients prior to initiation of systemic treatment and 8 weeks after therapy initiation. Treatment response was evaluated separately on 18F-PSMA-PET and CT. Changes on PSMA-PET (SUVmean) were assessed on a per patient basis using a modified PERCIST scoring system. Complete response (CRPET) was defined as absence of any uptake in all target lesions on posttreatment PET. Partial response (PRPET) was defined as decrease in summed SUVmean of > 30%. The appearance of new, PET-positive lesions or an increase in summed SUVmean of > 30% was defined as progressive disease (PDPET). A change in summed SUVmean of ± 30% defined stable disease (SDPET). RECIST 1.1 criteria were used for response assessment on CT. Results of radiographic response assessment on PSMA-PET and CT were compared. RESULTS: Overall, 11 mRCC patients undergoing systemic treatment were included. At baseline PSMA-PET1, all mRCC patients showed at least one PSMA-avid lesion. On follow-up PET2, 3 patients showed CRPET, 3 PRPET, 4 SDPET, and 1 PDPET. According to RECIST 1.1, 1 patient showed PRCT, 9 SDCT, and 1 PDCT. Overall, concordant classifications were found in only 2 cases (2 SDCT + PET). Patients with CRPET on PET were classified as 3 SDCT on CT using RECIST 1.1. By contrast, the patient classified as PRCT on CT showed PSMA uptake without major changes during therapy (SDPET). However, among 9 patients with SDCT on CT, 3 were classified as CRPET, 3 as PRPET, 1 as PDPET, and only 2 as SDPET on PSMA-PET. CONCLUSION: On PSMA-PET, heterogeneous courses were observed during systemic treatment in mRCC patients with highly diverging results compared to RECIST 1.1. In the light of missing biomarkers for early response assessment, PSMA-PET might allow more precise response assessment to systemic treatment, especially in patients classified as SD on CT.

Advanced Molecular Imaging in Histologically Verified Metanephric Adenoma.

Metanephric adenoma (MA) describes a rare renal tumor and is generally considered a benign lesion. However, there are cases with regional lymphogenic and distant metastases. Noninvasive diagnosis of MA using conventional imaging remains challenging. Here, we describe a case of histologically verified MA with additional advanced molecular imaging consisting of 18F-PSMA-1007 PET/CT, 99mTc-Sestamibi SPECT and contrast-enhanced ultrasound.

Adjuvant therapy in renal cell carcinoma: the perspective of urologists.

BACKGROUND: Until recently, there was no approved adjuvant therapy (AT) for renal cell carcinoma (RCC) unless sunitinib was approved in the US. We evaluated clinical opinion and estimated use regarding different treatment options and patient selection of AT in RCC patients based on current scientific data and individual experience in Germany. METHODS: We conducted an anonymous survey during a national urology conference in 01/2017. Answers of 157 urologists treating RCC patients could be included. Questions were related to practice setting, treatment of RCC, follow-up strategy, physicians' personal opinion and individually different important parameters regarding S-TRAC and ASSURE-trial. RESULTS: 82% were office based. 67% were located in larger cities. 83% reported that nephron-sparing surgery (NSS) was performed in tumors with diameter < 4 cm. Follow-up was done mainly in concordance with guideline recommendations. 68% treated an average of 2.9 patients/year with systemic therapy. Therapy was predominantly advocated using sunitinib (94%). Urologists were informed about S-TRAC and ASSURE-trial. For 47%, reported hazard ratio is the most important parameter to understand trial results followed by overall survival (OS) in 46%, disease-free survival in 38%, and results of other trials in 34%. The most convincing parameter to decide on AT is OS (69%). 62% placed their confidence in ASSURE over STRAC-trial. 44% would use AT for 12 months. Nodal involvement was the most common denominator for use of AT. 82% favor sunitinib as AT. CONCLUSIONS: A minority of urologists would use AT and are more confident in ASSURE-trial. Reluctance of prescribing AT mainly is based on lack of OS data and conflicting trial results.

[Follow-up of renal cell carcinoma in a nonmetastatic stage]. / Nachsorge beim Nierenzellkarzinom im nicht fernmetastasierten Stadium.

Postoperative follow-up care after curative surgery or ablative treatment is the standard of care in patients with nonmetastatic renal cell carcinoma. The goal is to identify and treat postoperative complications and local recurrences early on. Follow-up investigations and their relevance are widely acknowledged and validated and patients undergoing follow-up seem to benefit from a longer survival in nonmetastatic renal cell carcinoma. Hence there is no consensus on a standardized follow-up strategy. The most disputed question is around the frequency of the investigations and the duration of the follow-up. Without an evidence-based follow-up protocol, urologists should carry out an individualized, potentially lifelong follow-up regimen, which also includes the patients' needs and perspectives.

Adjuvant sunitinib in patients with high-risk renal cell carcinoma: safety, therapy management, and patient-reported outcomes in the S-TRAC trial.

Background: Adjuvant sunitinib has significantly improved disease-free survival versus placebo in patients with renal cell carcinoma at high risk of recurrence post-nephrectomy (hazard ratio 0.76; 95% confidence interval, 0.59-0.98; two-sided P = 0.03). We report safety, therapy management, and patient-reported outcomes for patients receiving sunitinib and placebo in the S-TRAC trial. Patients and methods: Patients were stratified by the University of California, Los Angeles Integrated Staging System and Eastern Cooperative Oncology Group performance status score, and randomized (1 : 1) to receive sunitinib (50 mg/day) or placebo. Single dose reductions to 37.5 mg, dose delays, and dose interruptions were used to manage adverse events (AEs). Patients' health-related quality of life, including key symptoms typically associated with sunitinib, were evaluated with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Results: Patients maintained treatment for 9.5 (mean, SD 4.4) and 10.3 (mean, SD 3.7) months in the sunitinib and placebo arms, respectively. In the sunitinib arm, key AEs occurred ∼1 month (median) after start of treatment and resolved within ∼3.5 weeks (median). Many (40.6%) AEs leading to permanent discontinuation were grade 1/2, and most (87.2%) resolved or were resolving by 28 days after last treatment. Patients taking sunitinib showed a significantly lower EORTC QLQ-C30 overall health status score versus placebo, although this reduction was not clinically meaningful. Patients reported symptoms typically related to sunitinib treatment with diarrhea and loss of appetite showing clinically meaningful increases. Conclusions: In S-TRAC, AEs were predictable, manageable, and reversible via dose interruptions, dose reductions, and/or standard supportive medical therapy. Patients on sunitinib did report increased symptoms and reduced HRQoL, but these changes were generally not clinically meaningful, apart from appetite loss and diarrhea, and were expected in the context of known sunitinib effects. Clinical trial registration: ClinicalTrials.gov, NCT00375674.

A new setup for the quantitative analysis of drying by the use of gas-phase FTIR-spectroscopy.

Drying rates are important for the manufacture of thin films and in specific for the production of electrodes used in electrochemical devices such as fuel cells and electrolyzers. The known procedures to investigate time-dependent sample compositions and selective evaporation rates are insufficient to obtain mean information about the full area instead of a single point analysis. Therefore, a new setup is presented using gas-phase Fourier-transform infrared spectroscopy. This method analyzes the gas-phase composition to recalculate the layer composition in electrode fabrication at any time during drying. According to the golden rule of measurement technology, manufacturer specifications are often overestimated. Therefore, our alternative procedures were used to evaluate the precision of devices used. The calculated measurement precision is confirmed by validation. The expected deviation is quantified to be less than 2% for the common application. Further on, the relative test-retest standard deviation is determined to be 0.3%-0.4%. As a result of the error propagation, the measurement precision is limited by the background gas flow rate precision for common application. At low volume fractions, the influence of the substance flow rate deviations becomes significant. However, further studies will focus on increasing the gas flow rate precision.

[Epidemiology and diagnostic assessment of small renal masses]. / Epidemiologie und Diagnostik kleiner Nierentumoren.

BACKGROUND: The incidence of small renal masses has been rising over the last few decades. At the same time, mortality of renal cell carcinoma (RCC) is decreasing. These trends can be explained by the availability of improved therapeutic measures and the good prognosis of small renal masses (SRM) turning out to be histopathologically benign or of low malignancy in many cases. OBJECTIVES: The aim of this article is to present epidemiology and diagnostic assessment of SRM. MATERIALS AND METHODS: Statistics, basic research, guidelines. RESULTS: The incidence of SRM is rising due to the widespread use of imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and contrast-enhanced ultrasound (CEUS). Sensitivity is excellent for CEUS and for CECT in the characterization of SRM, while good specificity values can be reached by MRI. For characterization of complex cystic renal masses, CEUS has good diagnostic accuracy. CONCLUSIONS: Due to improved diagnostic possibilities, SRMs can be diagnosed in early asymptomatic stages. As SRM have a good prognosis and often are of low malignancy therapy, options should be carefully considered; especially in older patients, active surveillance should considered.

Recommendations on managing lenvatinib and everolimus in patients with advanced or metastatic renal cell carcinoma.

INTRODUCTION: There are several second-line treatment options for patients with renal cell carcinoma after first-line failure of a tyrosine kinase inhibitor, especially with the recent approvals of cabozantinib, nivolumab, and the lenvatinib plus everolimus combination. A lack of reliable biomarkers and an overall lack of prospective head-to-head comparisons make it a challenge to choose a second-line treatment in the clinic. Areas covered: In this review/meta-opinion, we describe the safety profile of the lenvatinib plus everolimus combination in renal cell carcinoma. The combination of lenvatinib plus everolimus has achieved the highest rates of objective responses and the longest progression free and overall survival in cross-comparison trials. At the same time, the safety profile of this combination, including the rate of total and severe adverse events, the percentage of dose reductions required, and the rate of treatment discontinuation, was less favorable compared with available monotherapy options, suggesting that better management could help to maximize the activity of this combination while protecting patients from undue harm. Expert opinion: Herein, we aim to postulate multidisciplinary recommendations on the advice to offer to patients and caregivers before starting treatment and how to manage the combination from the perspective of daily clinical practice.

Clinical Usage of Different Guidelines in Routine Management, Therapy and Follow-Up of Patients with Renal Cell Cancer in Germany.

OBJECTIVES: To evaluate the usage of different guidelines and to estimate the impact of changed recommendation in routine management, therapy and follow-up of patients with renal cell cancer (RCC). METHODS: An anonymous questionnaire was sent to 600 urologists in Germany. Twenty-seven percent of them were included in the analysis. The questions were about the practice setting, surgical and medical treatment of RCC, follow-up modalities, knowledge and usage of RCC guidelines. Results were correlated with the recommendations of the EAU-guideline. RESULTS: Sixty-eight percent of the urologists were office based. Sixty percent were located in bigger cities. Ninety-eight percent of the colleagues reported to be knowledgeable about the EAU-guidelines, 62% reported to know the American Urological Association, 59% DGU/AWMF, 19% National Comprehensive Cancer Network, 19% European Society for Medical Oncology, 13% Onkopedia, and 3% British Association of Urological Surgeons-guidelines. Eighty-seven percent reported that partial nephrectomy (Nx) was performed in tumours with diameter <4 cm. Forty-one percent performed a radical Nx for tumours that were 4-7 cm. Follow-up of RCC was done in 99%. Fifty-nine percent underwent an abdominal CT scan after 6 months. Thirty-nine percent got a chest X-ray done. Among those with metastatic RCC, only 84% were offered systemic therapy. First-line therapy was predominantly advocated using sunitinib. CONCLUSION: Almost all urologists know and use the EAU-guidelines. Other guidelines are rarely used. Follow-up is performed in discordance with the EAU-recommendations. Interestingly, only 84% with metastatic disease are introduced to systemic therapy.

Renal Pseudoaneurysms and Arteriovenous Fistulas as a Complication of Nephron-Sparing Partial Nephrectomy: Technical and Functional Outcomes of Patients Treated With Selective Microcoil Embolization During a Ten-Year Period.

PURPOSE: The aim of this study was to evaluate the clinical and functional outcomes in patients who underwent selective interventional embolization of renal pseudoaneurysms or arteriovenous fistulas at our center. MATERIALS AND METHODS: Our retrospective analysis included all consecutive patients who received selective transcatheter embolization of renal pseudoaneurysms or arteriovenous fistulas after partial nephrectomy in our department from January, 2003 to September, 2013. The technical and clinical success rate and functional outcome of every procedure was collected and analyzed. Furthermore, the change in renal parenchymal volume before and after embolization was determined in a subgroup. RESULTS: A total of 1425 patients underwent partial nephrectomy at our hospital. Of these, 39 (2.7 %) were identified with a pseudoaneurysm or an arteriovenous fistula after partial nephrectomy. The diagnosis of the vascular lesions was made by means of biphasic CT or CEUS. Technical success by means of selective microcoil embolization was achieved in all 39 patients (100 %). Clinical success, defined as no need for further operation or nephrectomy during follow-up, was achieved in 35 of 39 patients (85.7 %). Renal function, as measured by eGFR before and after the intervention, did not change significantly. However, a mean loss of parenchymal volume of 25.2 % was observed in a subgroup. No major or minor complications were attributable to the embolization procedure. CONCLUSION: Transcatheter embolization is a promising method for treating vascular complications which may occur after partial nephrectomy. We confirm the high success rate of this technique while discussing renal functional outcomes and potential safety aspects. KEY POINTS: Arterial pseudoaneurysms and arteriovenous fistulas are rare but severe complications after partial nephrectomy. Selective microcoil embolization is a safe and effective kidney-preserving procedure for treating these complications. Embolization leads to a significant loss of renal parenchymal volume but not to a loss of renal function.

Dual energy can accurately differentiate uric acid-containing urinary calculi from calcium stones.

PURPOSE: To retrospectively evaluate the accuracy of dual-energy CT (DECT) in the detection of the chemical composition of urinary calculi in correlation with infrared spectroscopic stone analysis. METHODS: We reviewed the CT scans of 255 patients who underwent DECT due to a clinical suspicion of urolithiasis. Out of this group, we included 64 patients with clinically symptomatic urolithiasis requiring stone removal. After surgical removal of the stone by ureterorenoscopy, chemical composition was analyzed with infrared spectroscopy. We correlated DECT stone characterization results with chemical stone composition based on dual-energy indices (DEI). A total of 213 renal and ureteral stones could be removed and chemically analyzed. RESULTS: A total of 213 calculi were evaluated. Thirty eight out of sixty four (59 %) patients had >1 stone. DECT was used to differentiate stones by using DEI. Stones harboring calcium (CA) were color-coded in blue, while stones containing uric acid (UA) were colored red. Median DEI in UA-containing stones were 0.001. Non-UA-containing stones had a DEI between 0.073 for pure CA stones and 0.077 containing CA and other substances (p = 0.001; p = 0.03, respectively). Sensitivity of DECT was 98.4 % for differentiation of UA from non-UA-containing calculi. Specificity was 98.1 %. Mean effective radiation dose of DECT was 4.18 mSv (0.44-14.27 mSv), thus comparable to conventional CT scans of the abdomen. Conventional measurement of Hounsfield units did not correlate with stone composition. CONCLUSION: DECT with image post-processing reliably discriminates UA-containing calculi from all other stones, but the study offered limitations. Discrimination within the non-UA stones cannot be reliably achieved but is clinically insignificant.

Characterization of histological subtypes of clear cell renal cell carcinoma using contrast-enhanced ultrasound (CEUS).

INTRODUCTION: The aim of this study was to analyze the histological subtypes of clear cell renal cell carcinoma (RCC) examined by means of contrast-enhanced ultrasound (CEUS) and a second generation blood pool agent (SonoVue®, Bracco, Milan, Italy) during the pre-operative phase. MATERIALS AND METHODS: 29 patients with histologically proven subtypes of clear cell RCC were examined. A total of three patients were diagnosed with highly differentiated clear cell RCC, 21 out of 29 cases with moderately differentiated clear cell RCC and five out of 29 patients had insufficiently differentiated clear cell RCC. An experienced radiologist examined the patients with CEUS. The following parameters were analyzed: maximum signal intensity (PEAK), time elapsed until PEAK is reached (MTT), local blood flow (RBF), area under the time intensity curve (AUC) and the signal intensity (SI) during the course of time. For the groups all comparisons are made based on healthy renal parenchyma. RESULTS: In the clear cell RCC significant differences (significance level p < 0.05) between cancerous tissue and the healthy renal parenchyma were noticed in all four parameters. Therefore, the clear cell RCC stands out due to its reduced blood volume. However, it reached the PEAK reading relatively rapidly and its signal intensity was always lower than that of the healthy renal parenchyma. In the arterial phase retarded absorption of the contrast agent was observed, followed by fast washing out of the contrast agent bubbles.In all three histological subgroups no significant differences were noticed in PEAK and SI. However, the diagrams showed the possible bias, that the group of the insufficiently differentiated clear cell RCC had the highest PEAK-value and the highest signal intensity when compared with highly and moderately differentiated clear cell RCC. CONCLUSION: Our study suggests that CEUS may be an additional tool for non-invasive characterisation and differentiation of the three histological subtypes of clear cell RCC. Furthermore, it seems to have an additional diagnostic value in daily clinical.

Parametric imaging of clear cell and papillary renal cell carcinoma using contrast-enhanced ultrasound (CEUS).

PURPOSE: The aim of this study was to analyse clear cell and papillary renal cell carcinoma (RCC) examined with contrast-enhanced ultrasound (CEUS) and a second generation blood pool agent (SonoVue®, Bracco, Milan, Italy) before clinical intervention. MATERIALS AND METHODS: A total of 41 patients with histologically proven subtypes of RCC were examined. 29 patients had a clear cell RCC and 12 patients showed a papillary RCC. Average size in the clear cell RCC group was 6.07 cm and 1.88 cm in the papillary RCC group. An experienced radiologist examined all patients with CEUS. The following parameters were analysed: maximum signal intensity (PEAK), time elapsed until PEAK is reached (MTT), local blood flow (RBF), area under the time intensity curve (AUC) and the signal intensity (SI) during the course of time. For both groups all comparisons were made based on healthy renal parenchyma. RESULTS: In the clear cell RCC significant differences (significance level p < 0.05) between cancerous tissue and the healthy renal parenchyma were noticed in all four parameters. The clear cell RCC showed a significant reduced blood volume. It reached the PEAK reading relatively rapidly and its signal intensity was always lower than that of the healthy renal parenchyma. In the arterial phase retarded absorption of the contrast agent was observed, followed by fast washing out of the contrast agent bubbles.In the papillary RCC group, significant findings as to PEAK and RBF as well as a slightly significant difference as to AUC were recorded. The papillary RCC had a lower blood supply and reached its PEAK reading later. Its signal intensity was also reduced. The signal intensity of papillary NCC was significantly lower compared with clear cell RCC; absorption and washing out of the contrast agent was delayed. CONCLUSION: CEUS seems to be an useful additional method to clinically differentiate between clear cell and papillary RCC. In daily clinical use, patients with contraindication for other imaging methods, especially the magnetic resonance imaging, might particularly benefit from this method.

[Cross-sectional imaging evaluation of renal masses]. / Schnittbildgebung der Nierentumoren.

Cross-sectional imaging modalities including multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) are the diagnostic standard in detection, characterization, and staging of renal masses due to their high sensitivity and specificity. Currently, most renal masses are incidentally diagnosed by imaging for other medical reasons. Recent developments have improved image acquisition with high resolution, while simultaneously reducing radiation dose. CT imaging is the most accessible cross-sectional imaging method and is, therefore, the standard technique. MRI is indicated in patients who are allergic to intravenous CT contrast medium, in patients with renal insufficiency, or in younger patients. Further characterization of renal masses is possible with functional imaging including dual energy CT, perfusion CT, or diffusion-weighted MRI. Contrast-enhanced ultrasound allows detection of even subtle enhancement in hypovascular lesions with high sensitivity and can add valuable information to CT and MRI studies.

Axitinib versus sorafenib in advanced renal cell carcinoma: subanalyses by prior therapy from a randomised phase III trial.

BACKGROUND: In the AXIS trial, axitinib prolonged progression-free survival (PFS) vs sorafenib in patients with advanced renal cell carcinoma (RCC) previously treated with sunitinib or cytokines. METHODS: In post hoc analyses, patients were grouped by objective response to prior therapy (yes vs no), prior therapy duration (< vs ⩾median), and tumour burden (baseline sum of the longest diameter < vs ⩾median). PFS and overall survival (OS), and safety by type and duration of prior therapy were evaluated. RESULTS: Response to prior therapy did not influence outcome with second-line axitinib or sorafenib. PFS was significantly longer in axitinib-treated patients who received longer prior cytokine treatment and sorafenib-treated patients with smaller tumour burden following sunitinib. Overall survival with the second-line therapy was longer in patients who received longer duration of prior therapy, although not significant in the sunitinib-to-axitinib sequence subgroup; OS was also longer in patients with smaller tumour burden, but not significant in the cytokine-to-axitinib sequence subgroup. Safety profiles differed modestly by type and duration of prior therapy. CONCLUSIONS: AXIS data suggest that longer duration of the first-line therapy generally yields better outcome with the second-line therapy and that lack of response to first-line therapy does not preclude positive clinical outcomes with a second-line vascular endothelial growth factor-targeted agent in patients with advanced RCC.

A new concept for early recovery after surgery for patients undergoing radical cystectomy for bladder cancer: results of a prospective randomized study.

PURPOSE: Early recovery after surgery concepts have gained wide acceptance in various surgical specialties. However, limited data are available for radical cystectomy. A new early recovery after surgery concept was compared to a more conservative regimen in patients undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS: A total of 101 consecutive patients were prospectively randomized to early recovery after surgery (62) or a conservative regimen (39) (intended randomization ratio was 2 early recovery after surgery-to-1 conservative regimen). Primary end points were differences in quality of life, and secondary end points included postoperative morbidity, demand for analgesics, time spent in the intermediate care unit, mobility and number of gastrointestinal events during hospital stay. RESULTS: Quality of life parameters, as measured by the EORTC (European Organization for the Research and Treatment of Cancer) Quality of Life questionnaire QLQ-30 did not change significantly between postoperative days 3 and 7 and at discharge from hospital in the conservative regimen group, whereas a significant improvement was observed in the early recovery after surgery group. Postoperative morbidity was lower in the early recovery after surgery group in terms of wound healing disorders (p = 0.006), fever (p = 0.004) and thrombosis (p = 0.027). The demand for analgesics was significantly lower in the early recovery after surgery group. The amount of food consumed in relation to the amount of food offered was significantly higher for the early recovery after surgery group as early as day 3 (p = 0.02). Time spent in the intermediate care unit was significantly shorter for the early recovery after surgery group (p <0.001). There were no significant differences between the groups with respect to gastrointestinal events. The main limitations of this study were the lack of long-term data as well as the single center approach. CONCLUSIONS: Early recovery after surgery of patients who underwent radical cystectomy appears to have significant benefits compared to a conservative regimen in terms of postoperative morbidity, quality of life, use of analgesics and time spent in the intermediate care unit.

A multinational phase II trial of bevacizumab with low-dose interferon-α2a as first-line treatment of metastatic renal cell carcinoma: BEVLiN.

BACKGROUND: Avastin and Roferon in Renal Cell Carcinoma (AVOREN) demonstrated efficacy for bevacizumab plus interferon-α2a (IFN; 9 MIU tiw) in first-line metastatic renal cell carcinoma (mRCC). We evaluated bevacizumab with low-dose IFN in mRCC to determine whether clinical benefit could be maintained with reduced toxicity. METHODS: BEVLiN was an open-label, single-arm, multinational, phase II trial. Nephrectomized patients with treatment-naive, clear cell mRCC and favourable/intermediate Memorial Sloan-Kettering Cancer Center scores received bevacizumab (10 mg/kg every 2 weeks) and IFN (3 MIU thrice weekly) until disease progression. Descriptive comparisons with AVOREN patients having favourable/intermediate MSKCC scores treated with bevacizumab plus IFN (9 MIU) were made. Primary end points were grade ≥3 IFN-associated adverse events (AEs) and progression-free survival (PFS). All grade ≥3 AEs and bevacizumab/IFN-related grade 1-2 AEs occurring from first administration until 28 days after last treatment were reported. RESULTS: A total of 146 patients were treated; the median follow-up was 29.4 months. Any-grade and grade ≥3 IFN-associated AEs occurred in 53.4% and 10.3% of patients, respectively. The median PFS and overall survival were 15.3 [95% confidence interval (CI): 11.7-18.0] and 30.7 months (95% CI: 25.7-not reached), respectively. The ORR was 28.8%. CONCLUSIONS: Compared with a historical control AVOREN subgroup, low-dose IFN with bevacizumab resulted in a reduction in incidence rates of IFN-related AEs, without compromising efficacy [NCT00796757].

[Partial nephrectomy. Rationale and limitations of an organ-preserving approach]. / Partielle Tumornephrektomie. Sinn und Grenzen des Organerhalts.

The rising incidence of renal cell cancer in recent decades has led to a revision in the therapy of this malignancy. For small renal masses, partial nephrectomy has become the standard surgical treatment instead of radical nephrectomy. This approach can lead to a higher overall survival due to preservation of renal function. Avoiding chronic kidney disease is mandatory for patients with benign or small non-aggressive tumors; however, partial nephrectomy correlates with higher complication rates and is conditioned by operator skills. The role of partial nephrectomy compared to radical nephrectomy is still to be established particularly for larger tumors. The results of studies so far are mostly based on non-randomized retrospective data. This article will present the pros and cons of partial nephrectomy and will focus on the steps required to promulgate the indications of nephron-sparing surgery.