The extent of lymphadenectomy seems to be associated with better survival in patients with nonmetastatic upper-tract urothelial carcinoma: how many lymph nodes should be removed?

Background: The role and extent of lymphadenectomy in patients with upper-tract urothelial carcinoma (UTUC) is debated.

Objective: To establish whether the number of lymph nodes (LNs) removed might be associated with better cause-specific survival in patients with UTUC.

Design, Setting, And Participants: The study included 552 consecutive patients who underwent radical nephroureterectomy (RNU) and lymphadenectomy between 1992 and 2006.

Cytoreductive nephrectomy for metastatic RCC in the era of targeted therapy.

Metastatic renal cell carcinoma (RCC) has traditionally been associated with a poor prognosis with few effective treatments. In the multimodal treatment of metastatic RCC, cytoreductive nephrectomy (CN) became the standard of care after two randomized trials demonstrated a benefit in overall survival in patients who received CN prior to treatment with interferon. More recently, several agents (sunitinib, sorafenib, temsirolimus, everolimus and bevacizumab) have been developed that target angiogenesis and the cellular growth pathways involved in metastatic RCC.

Genome-wide profiling of chromosomal alterations in renal cell carcinoma using high-density single nucleotide polymorphism arrays.

The identification of genetic aberrations may help understand the mechanisms of tumorigenesis and has important implications in diagnosis, prognosis and treatment. We applied Illumina's 317K high-density single nucleotide polymorphism (SNP) arrays to profile chromosomal aberrations in clear cell renal cell carcinoma (ccRCC) from 80 patients and analyzed the association of LOH/amplification events with clinicopathological characteristics and telomere length. The most common loss of heterozygosity (LOH) were 3p (69 cases) including 38 whole 3p arm losses, 30 large fragment LOH (spanning 3p21-36), and 1 interstitial LOH (spanning 3p12-14, 3p21-22, 3p24.

Papillary renal cell carcinoma: radiologic-pathologic correlation and spectrum of disease.

Papillary renal cell carcinoma (pRCC) is the second most common type of renal cell carcinoma (RCC). pRCC has unique imaging and clinical features that may allow differentiation from clear cell RCC (cRCC). There have been significant advances in our knowledge of the natural history and treatment of pRCC, with data suggesting that it may be best to manage pRCC differently from the other subtypes of RCC.

Neoadjuvant (presurgical) therapy for renal cell carcinoma: a new treatment paradigm for locally advanced and metastatic disease.

Background: Although upfront cytoreductive nephrectomy followed by systemic therapy remains the standard of care for metastatic renal cell carcinoma, the addition of novel targeted therapy has prompted a reevaluation of this treatment paradigm. The authors reviewed their experience with neoadjuvant systemic therapy administered before cytoreductive surgery for metastatic, locally recurrent, or regionally advanced renal cell carcinoma.

Methods: The authors compared patients treated with presurgical targeted therapy (with sunitinib, sorafenib, or bevacizumab) with a contemporary group that underwent up-front cytoreductive surgery.

Innovations and challenges in renal cancer: summary statement from the Third Cambridge Conference.

The Third Cambridge Conference on Innovations and Challenges in Renal Cancer, a symposium held in Cambridge, Massachusetts, June 27-28, 2008, and chaired by Michael B. Atkins, was convened to discuss the current state of knowledge in the field, critique new data, stimulate communication among those involved in basic and clinical research, and offer recommendations for further study. Four main topics were discussed: genetics and molecular biology of renal cell cancer, staging and prognosis, systemic therapy, and correlative science and biomarkers in stage IV disease.

Impact of lymph node dissection on cancer specific survival in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

Purpose: We examined the impact of lymphadenectomy on the clinical outcomes of patients with upper tract urothelial cancer treated with radical nephroureterectomy.

Materials And Methods: Data were collected on 1,130 consecutive patients with pT1-4 upper tract urothelial cancer treated with radical nephroureterectomy at 13 centers worldwide. Patients were grouped according to nodal status (pN0 vs pNx vs pN+).

Comparison of oncologic outcomes for open and laparoscopic nephroureterectomy: a multi-institutional analysis of 1249 cases.

Background: Data regarding the oncologic efficacy of laparoscopic nephroureterectomy (LNU) compared to open nephroureterectomy (ONU) are scarce.

Objective: We compared recurrence and cause-specific mortality rates of ONU and LNU.

Design, Setting, And Participants: Thirteen centers from three continents contributed data on 1249 patients with nonmetastatic upper tract urothelial carcinoma (UTUC).

Prospective assessment of systemic therapy followed by surgical removal of metastases in selected patients with renal cell carcinoma.

Objective: To prospectively establish objective selection criteria for metastasectomy in patients with metastatic renal cell carcinoma (mRCC).

Patients And Methods: Between 1991 and 1999, 38 patients with mRCC with responsive or stable disease after initial systemic therapy, and with potentially resectable disease, were enrolled. Patients had a metastasectomy with curative intent and received consolidative adjuvant systemic therapy.

Predictors of oncological outcome after resection of locally recurrent renal cell carcinoma.

Purpose: Local renal cell carcinoma recurrence is rare after radical nephrectomy with curative intent. We examined our experience to describe the natural history of isolated local recurrence and characterize important prognostic factors that predict the outcome in patients treated with aggressive resection.

Materials And Methods: In an institutional database of 4,800 patients with renal cell carcinoma, of whom 2,945 underwent radical nephrectomy with curative intent, 54 were subsequently found to have isolated local recurrence in the renal fossa, ipsilateral adrenal gland or ipsilateral retroperitoneal lymph nodes, which was managed by surgical resection.

Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer.

Background: Secondary analyses of two randomized, controlled phase III trials demonstrated that selenium and vitamin E could reduce prostate cancer incidence. To characterize pharmacodynamic and gene expression effects associated with use of selenium and vitamin E, we undertook a randomized, placebo-controlled phase IIA study of prostate cancer patients before prostatectomy and created a preoperative model for prostatectomy tissue interrogation.

Methods: Thirty-nine men with prostate cancer were randomly assigned to treatment with 200 microg of selenium, 400 IU of vitamin E, both, or placebo.

Family history and risk of renal cell carcinoma: results from a case-control study and systematic meta-analysis.

We conducted a case-control analysis, a family-based population analysis, and a meta-analysis to assess the role of family history of cancer and kidney cancer in association with the risk of renal cell carcinoma (RCC). A total of 325 cases and 329 controls were identified from an ongoing case-control study of RCC. Study variables were assessed through 45-minute structured face-to-face interviews.

Sensitivity to NNKOAc is associated with renal cancer risk.

Cigarette smoking has been investigated as a major risk factor for renal cell carcinoma (RCC). 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most abundant carcinogenic N-nitrosamines present in cigarette smoke. However, the association between repair capacity of NNK-induced DNA damage and RCC risk remains unknown.

Should patients undergoing surgery for renal cell carcinoma have a lymph node dissection?

While several retrospective studies have suggested a possible benefit of lymph node dissection (LND) for patients with clinically node-positive renal cell carcinoma (RCC), the value of LND in patients with clinically node-negative RCC has remained uncertain. LND undoubtedly improves the accuracy of staging and provides better prognostic information; however, much debate surrounds the impact of LND on progression-free and overall survival in patients with RCC. Additionally, the question remains as to whether LND at nephrectomy is associated with increased morbidity.

Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration.

Background: The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified.

Methods: Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected.

Long-term outcome for men with teratoma found at postchemotherapy retroperitoneal lymph node dissection.

Background: Patients with pure teratoma within the postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimen traditionally have been considered at low risk for disease progression. The objectives of this study were to determine the disease-related outcomes of patients who had pure teratoma identified at the time of PC-RPLND and to examine the prognostic value of clinical variables that were identified previously as important predictors of disease recurrence in these patients.

Methods: Between 1980 and 2003, 97 patients with metastatic nonseminomatous germ cell tumor and pure teratoma histology at the time of PC-RPLND were identified.

Cytoplasmic sequestration of p27 via AKT phosphorylation in renal cell carcinoma.

Purpose: p27 localization and expression has prognostic and predictive value in cancer. Little is known regarding expression patterns of p27 in renal cell carcinoma (RCC) or how p27 participates in disease progression or response to therapy.

Experimental Design: RCC-derived cell lines, primary tumors, and normal renal epithelial cells were analyzed for p27 expression, phosphorylation (T157 of the NLS), and subcellular localization.

Lymphovascular invasion predicts clinical outcomes in patients with node-negative upper tract urothelial carcinoma.

Purpose: To assess the association of lymphovascular invasion (LVI) with cancer recurrence and survival in a large international series of patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC).

Patients And Methods: Data were collected on 1,453 patients treated with RNU at 13 academic centers and combined into a relational database. Pathologic slides were rereviewed by genitourinary pathologists according to strict criteria.

Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma.

Purpose: MicroRNAs (miRNA) are a class of small noncoding RNA molecules that have been implicated in a wide variety of basic cellular functions through posttranscriptional regulations on their target genes. Compelling evidence has shown that miRNAs are involved in cancer initiation and progression. We hypothesized that genetic variations of the miRNA machinery genes could be associated with the risk of renal cell carcinoma.

Neoadjuvant platelet derived growth factor receptor inhibitor therapy combined with docetaxel and androgen ablation for high risk localized prostate cancer.

Purpose: Platelet derived growth factor receptor inhibitor therapy improves the efficacy of taxane chemotherapy in preclinical models of prostate cancer. Men with high risk localized prostate cancer were treated with platelet derived growth factor receptor inhibitor therapy, docetaxel and hormone ablation in the preoperative setting, and clinicopathological outcomes were evaluated.

Materials And Methods: A total of 36 men with cT2 or greater disease, Gleason grade 8-10, serum prostate specific antigen more than 20 ng/ml or cT2b and prostate specific antigen more than 10 ng/ml and Gleason 7 disease, without radiological evidence of metastases, were scheduled to receive intramuscular leuprolide, 600 mg daily oral imatinib and 30 mg/m(2) weekly docetaxel x 4 every 42 days for 3 cycles before radical prostatectomy (beta [0.

Pre-surgical targeted molecular therapy in renal cell carcinoma.

Pre-surgical systemic therapy with targeted molecular agents is an attractive option as an approach to the treatment of patients with renal cell carcinoma. This treatment strategy offers a rational approach for selecting patients with metastatic disease who are most likely to benefit from cytoreductive nephrectomy, but also allows access to treated tumour tissue to study the molecular mechanisms of response and resistance. In patients with locally advanced disease, this strategy offers the potential for improved resectability and timely delivery of systemic therapy to treat subclinical metastatic disease.

Risk stratification of patients with nodal involvement in upper tract urothelial carcinoma: value of lymph-node density.

Objective: To determine the risk factors associated with clinical outcome in patients with lymph node (LN)-positive urothelial carcinoma of the upper urinary tract (UTUC) treated with radical nephroureterectomy (RNU) and lymphadenectomy, focusing on the concept of LN density (LND).

Patients And Methods: Patients undergoing RNU with regional lymphadenectomy were identified through multi-institutional databases. All pathology slides were re-evaluated by genitourinary pathologists unaware of the clinical data.

Tumour architecture is an independent predictor of outcomes after nephroureterectomy: a multi-institutional analysis of 1363 patients.

Objective: To assess whether tumour architecture can help to refine the prognosis of patients treated with nephroureterectomy (NU) for urothelial carcinoma (UC) of the upper urinary tract (UT), as the prognostic value of tumour architecture (papillary vs sessile) in UTUC remains elusive.

Patients And Methods: The study included 1363 patients with UTUC and treated with radical NU at 12 centres worldwide. All slides were re-reviewed according to strict criteria by genitourinary pathologists who were unaware of the findings of the original pathology slides and clinical outcomes.

Randomized trial of adjuvant thalidomide versus observation in patients with completely resected high-risk renal cell carcinoma.

Objectives: To evaluate the effect of adjuvant thalidomide on recurrence-free survival (RFS) after nephrectomy for high-risk metastatic renal cell carcinoma (RCC).

Methods: Eligibility criteria for enrollment on this randomized trial included any histologic subtype, T2 (high grade, any N), T3/T4 (any grade, any N), or node-positive (any grade, any T) RCC. We randomized eligible patients to observation or to receive thalidomide 300 mg daily for 24 months.