Challenging the treatment paradigm for advanced renal cell carcinoma: a review of systemic and localized therapies.

The current standard of care for the management of advanced renal cell carcinoma (RCC) revolves around systemic therapy with molecularly targeted agents. Over the last decade, a total of seven targeted drugs have been approved but, altogether, only exploit two molecular targets in this disease: the vascular endothelial growth factor (VEGF) axis and the mammalian target of rapamycin (mTOR). Introduction of these agents has markedly improved outcomes compared with those in the cytokine era, yet comparatively little progress has been made since registration of the first targeted therapeutics occurred 10 years ago.

EAU guidelines on renal cell carcinoma: 2014 update.

Context: The European Association of Urology Guideline Panel for Renal Cell Carcinoma (RCC) has prepared evidence-based guidelines and recommendations for RCC management.

Objectives: To provide an update of the 2010 RCC guideline based on a standardised methodology that is robust, transparent, reproducible, and reliable.

Evidence Acquisition: For the 2014 update, the panel prioritised the following topics: percutaneous biopsy of renal masses, treatment of localised RCC (including surgical and nonsurgical management), lymph node dissection, management of venous thrombus, systemic therapy, and local treatment of metastases, for which evidence synthesis was undertaken based on systematic reviews adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.

[Ischemia is not an independent predictive factor of chronic renal failure after partial nephrectomy in a solitary kidney in patients without pre-operative renal insufficiency].

Objective: To assess the influence of vascular clamping and ischemia time on long-term post-operative renal function following partial nephrectomy (PN) for cancer in a solitary kidney.

Patients And Methods: This is a retrospective study including 259 patients managed by PN between 1979 and 2010 in 13 centers. Clamping use, technique choice (pedicular or parenchymal clamping), ischemia time, and peri-operative data were collected.

Local treatments for metastases of renal cell carcinoma: a systematic review.

Local treatment of metastases such as metastasectomy or radiotherapy remains controversial in the treatment of metastatic renal cell carcinoma. To investigate the benefits and harms of various local treatments, we did a systematic review of all types of comparative studies on local treatment of metastases from renal cell carcinoma in any organ. Interventions included metastasectomy, radiotherapy modalities, and no local treatment.

Single fraction radiosurgery for the treatment of renal tumors.

Purpose: High dose local stereotactic radiosurgery was performed in select patients to improve local tumor control and overall survival. We report on patients with renal tumors treated with single fraction robotic stereotactic radiosurgery.

Materials And Methods: A total of 40 patients with a median age of 64 years who had an indication for nephrectomy and subsequent hemodialysis were entered in a prospective case-control study of single fraction stereotactic radiosurgery.

A systematic review of sequencing and combinations of systemic therapy in metastatic renal cancer.

Context: The introduction of novel molecular-targeted agents has revolutionised the management of patients with metastatic renal cell carcinoma (mRCC). However, uncertainties remain over sequential or simultaneous combination therapies.

Objective: To systematically review relevant literature comparing the clinical effectiveness and harms of different sequencing and combinations of systemic targeted therapies for mRCC.

Carbonic anhydrase 9 expression increases with vascular endothelial growth factor-targeted therapy and is predictive of outcome in metastatic clear cell renal cancer.

Background: There is a lack of biomarkers to predict outcome with targeted therapy in metastatic clear cell renal cancer (mccRCC). This may be because dynamic molecular changes occur with therapy.

Objective: To explore if dynamic, targeted-therapy-driven molecular changes correlate with mccRCC outcome.

Follow-up after cystectomy: regularly scheduled, risk adjusted, or symptom guided? Patterns of recurrence, relapse presentation, and survival after cystectomy.

Aims: To evaluate the efficacy of follow-up based on the patterns of recurrence, relapse presentation and survival after cystectomy, and to define a risk adjusted follow-up schedule.

Patients And Methods: The records of 343 patients with regular follow-up after cystectomy were reviewed for primary site of recurrence, accompanying symptoms, means of recurrence diagnosis, and clinicopathological factors. Based on Cox proportional hazard models, and the results of imaging studies low and high risk groups are identified and a risk adjusted follow-up protocol is proposed.

Penile sparing surgery for penile cancer-does it affect survival?

Purpose: Management of squamous cell carcinoma of the penis changed in recent decades in favor of penile sparing surgery. We assessed whether penile sparing therapies were increasingly applied in our penile squamous cell carcinoma cohort with time and whether penile sparing affected 5-year cancer specific survival.

Materials And Methods: We reviewed the records of 1,000 patients treated between 1956 and 2012, of whom 859 with invasive tumors were eligible for analysis.

Lymphatic drainage from renal cell carcinoma along the thoracic duct visualized with SPECT/CT.

Background: Lymphatic drainage of renal cell carcinoma is unpredictable. Renal lymphatics directly joining the thoracic duct without traversing any lymph nodes have been described in cadaver studies, yet to date, this has never been visualized using functional imaging in vivo.

Methods And Results: Patients with renal tumors <10 cm (cT1-cT2) and clinical absence of metastases (cN0, cM0) took part in a prospective institutional review board approved study investigating sentinel node mapping.

A hybrid radioactive and fluorescent tracer for sentinel node biopsy in penile carcinoma as a potential replacement for blue dye.

Background: Sentinel node (SN) biopsy in penile cancer is typically performed using a combination of radiocolloid and blue dye. Recently, the hybrid radioactive and fluorescent tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was developed to combine the beneficial properties of both radio-guidance and fluorescence imaging.

Objective: To explore the added value of SN biopsy using ICG-(99m)Tc-nanocolloid in patients with penile carcinoma.

Assessing the response to targeted therapies in renal cell carcinoma: technical insights and practical considerations.

Context: The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to significant necrosis without significant reduction in tumour size. In addition, the vascular effects of antiangiogenic therapy may occur long before there is any reduction in tumour size.

Prostate sparing cystectomy for bladder cancer: 20-year single center experience.

Purpose: We evaluated long-term oncologic and functional results after prostate sparing cystectomy for bladder cancer.

Materials And Methods: A total of 120 patients with cT1-4N0-3 bladder cancer were treated with prostate sparing cystectomy between 1994 and 2013, of whom 110 had a followup of 2 years or greater and were eligible for analysis. To rule out tumor in the bladder neck, prostatic urethra or prostate cancer all patients underwent preoperative transurethral biopsy of the bladder neck and prostatic urethra, prostate specific antigen measurement and transrectal ultrasound with biopsies.

Induction chemotherapy followed by surgery in node positive bladder cancer.

Objective: To evaluate the outcome and prognostic factors of patients with node positive bladder cancer (NPBC), who were eligible for surgery and treated with induction chemotherapy.

Methods: All consecutive patients with NPBC, who were treated with at least 2 cycles of induction chemotherapy and initially scheduled for surgery, between 1990 and 2012, were identified from an institutional bladder cancer database. Induction chemotherapy consisted of MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) or gemcitabine with cisplatin (Gem/Cis) or carboplatin (Gem/Carbo).

The effect of VEGF-targeted therapy on biomarker expression in sequential tissue from patients with metastatic clear cell renal cancer.

Purpose: To investigate how biologically relevant markers change in response to antiangiogenic therapy in metastatic clear cell renal cancer (mRCC) and correlate these changes with outcome.

Experimental Design: The study used sequential tumor tissue and functional imaging (taken at baseline and 12-16 weeks) obtained from three similar phase II studies. All three studies investigated the role of VEGF tyrosine kinase inhibitors (TKI) before planned nephrectomy in untreated mRCC (n = 85).

Occult lymph node metastases in patients with carcinoma invading bladder muscle: incidence after neoadjuvant chemotherapy and cystectomy vs after cystectomy alone.

Objective: To investigate the effect of neoadjuvant chemotherapy (NAC) on the incidence of lymph node (LN) metastases in clinically node-negative (cN0) patients with carcinoma invading the bladder muscle (MIBC).

Patients And Methods: Between 1990 and 2012, 828 consecutive patients underwent radical cystectomy (RC) with extended pelvic LN dissection (ePLND), of whom 441 had cT2-4N0M0 stage disease. A total of 83 patients received NAC then underwent RC and 358 patients underwent RC only.

Refining the use of cytoreductive nephrectomy in metastatic renal cell carcinoma.

Cytoreductive nephrectomy (CN) was regarded standard of care for patients with metastatic renal cellcarcinoma (mRCC) in the cytokine era. After the introduction of therapies targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways, improved median survival and primary tumor responses are observed. Prognostic models have been validated and the clinical significance of tumor heterogeneity and histological subtypes has been recognized.

Contemporary management of regional nodes in penile cancer-improvement of survival?

Purpose: The management of regional nodes of penile squamous cell carcinoma has changed with time due to improved knowledge about diagnosis and treatment. To determine whether changes in the treatment of regional nodes have improved survival, we compared contemporary 5-year cancer specific survival of patients with squamous cell carcinoma of the penis with that of patients in previous cohorts.

Materials And Methods: In an observational cohort study of 1,000 patients treated during 56 years 944 were eligible for analysis.

Fusion of planning CT and cystoscopy images for bladder tumor delineation: a feasibility study.

Purpose: Bladder tumor delineation and localization during treatment are challenging problems in radiotherapy for bladder cancer. The purpose of this study is to investigate improvement of tumor delineation by the fusion of cystoscopy images with the planning CT-scan using lipiodol markers injected around the visible tumor during cystoscopy.

Methods: A registration method was developed for the fusion of cystoscopy images with a planning CT-scan and was tested on a phantom and retrospectively on the imaging data of four bladder cancer patients.

A prospective evaluation of VEGF-targeted treatment cessation in metastatic clear cell renal cancer.

Background: Vascular endothelial growth factor (VEGF)-targeted therapy is administered continuously until progression in metastatic clear cell renal cancer (mRCC). The role of intermittent therapy is under investigation. Preclinical data raise concerns about this approach.

Do targeted agents offer clinical benefit as presurgical therapy?

Introduction: In the era of targeted therapy, management of patients with primary metastatic renal cell carcinoma and the tumour in place is again under investigation in randomized controlled trials. Proper patient selection for cytoreductive nephrectomy (CN) remains challenging. Presurgical targeted therapy may have potential advantages in this setting.