Evolving role of cytoreductive nephrectomy in metastatic renal cell carcinoma of variant histology

PURPOSE OF REVIEW: Summarize current evidence for cytoreductive nephrectomy in patients with metastatic renal cell carcinoma (mRCC) of variant histology. RECENT FINDINGS: The mainstream treatment for advanced malignancy is systematic therapy, including chemotherapy, targeted therapy, and immunotherapy. Nonetheless, cytoreductive nephrectomy has been used in the management of mRCC including variant (nonclear cell) histology. Prospective data supported cytoreductive nephrectomy for clear cell mRCC in the cytokine immunotherapy era in the late 1990s. In the targeted therapy era, the practice of cytoreductive nephrectomy in nonclear and clear cell histology had been largely based on retrospective data, but a recent phase III trial showed that targeted therapy alone is noninferior to targeted therapy combined with cytoreductive nephrectomy, therefore, questioning the clinical benefit of cytoreductive nephrectomy in this context. However, this trial had excluded patient with nonclear cell histology. With the potential for checkpoint inhibitor combinations to achieve long-term complete durable response, cytoreductive nephrectomy is a subject of ongoing debate especially, in nonclear cell histology as those were excluded from prospective trials. SUMMARY: Data are very sparse in nonclear histology. Although retrospective data favor the use of cytoreductive nephrectomy in nonclear cell mRCC, clinicians must carefully select patients and balance risks of surgery and delayed systemic therapy

Systemic Therapies for the Management of Non–Clear Cell Renal Cell Carcinoma: What Works, What Doesn't, and What the Future Holds

Non–clear cell renal cell carcinoma (nccRCC) is a broad term that refers to a diverse group of tumors, each with its own distinct biologic and therapeutic profile. The management of nccRCCs is often based on extrapolating data from clinical trials in the more common clear cell renal cell carcinoma, but our emerging prospective and retrospective clinical experience in nccRCC allows us to make more precise recommendations tailored to each histology. The systemic therapy options for metastatic nccRCC include targeted therapies such as tyrosine kinase inhibitors, immune checkpoint inhibitors, and, for specific rare subtypes, cytotoxic chemotherapy. Each nccRCC histology may respond differently to these regimens, which makes accurate pathologic diagnosis imperative. In the present review, we discuss the available clinical and biological data that can help guide systemic therapy recommendations for specific nccRCC subtypes. © 2020 Elsevier Inc

Long-term survival outcomes of cytoreductive nephrectomy combined with targeted therapy for metastatic renal cell carcinoma: A systematic review and individual patient data meta-analysis

The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains controversial during the targeted therapy era. To reconcile the current literature, we analyzed the reported survival data at the individual patient level and compared the long-term survival outcomes of CN combined with targeted therapy vs. targeted therapy alone in patients with mRCC. We performed a systematic review of the literature using the MEDLINE, Scopus, and Cochrane Library databases (end-of-search date: 21 July 2020). We recuperated individual patient data from the Kaplan–Meier curves for overall (OS), progression-free (PFS), and cancerspecific survival (CSS) from each study. We subsequently performed one-stage frequentist and Bayesian random-effects meta-analyses using both Cox proportional hazards and restricted mean survival time (RMST) models. Two-stage random-effects meta-analyses were also performed as sensitivity analyses. A subgroup analysis was also performed to determine the effect of CN timing. Fifteen studies fulfilling our inclusion criteria were identified, including fourteen retrospective cohort studies and one randomized controlled trial. In the one-stage frequentist meta-analysis, the CN group had superior OS (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.54–0.62, p < 0.0001) and CSS (HR: 0.63, 95% CI: 0.53–0.75, p < 0.0001). No meaningful clinical difference was observed in PFS (HR: 0.90, 95% CI: 0.80–1.02, p = 0.09). One-stage Bayesian meta-analysis also revealed superior OS (HR: 0.59, 95% credibility interval [CrI]: 0.55–0.63) and CSS (HR: 0.63, 95% CrI: 0.53–0.75) in the CN group, while no meaningful clinical difference was detected in PFS (HR: 0.91, 95% CrI: 0.80–1.02). Similar results were obtained with the RMST models. The OS benefit was also noted in the two-stage meta-analyses models, and in the subgroup of patients who received upfront CN. The combination of CN and targeted therapy for mRCC may lead to superior long-term survival outcomes compared to targeted therapy alone. Careful patient selection based on prognostic factors is required to optimize outcomes. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Next-generation sequencing of translocation renal cell carcinoma reveals novel RNA splicing partners and frequent mutations of chromatin-remodeling Genes

10.1158/1078-0432.CCR-13-3036Clinical Cancer Research20154129-414

Linnaeus was right all along: <i>Ulva</i> and <i>Enteromorpha</i> are not distinct genera.

Ulva, one of the first Linnaean genera, was later circumscribed to consist of green seaweeds with distromatic blades, and Enteromorpha Link was established for tubular forms. Although several lines of evidence suggest that these generic constructs are artificial, Ulva and Enteromorpha have been maintained as separate genera. Our aims were to determine phylogenetic relationships among taxa currently attributed to Ulva, Enteromorpha, Umbraulva Bae et I.K. Lee and the monotypic genus Chloropelta C.E. Tanner, and to make any nomenclatural changes justified by our findings. Analyses of nuclear ribosomal internal transcribed spacer DNA (ITS nrDNA) (29 ingroup taxa including the type species of Ulva and Enteromorpha), the chloroplast-encoded rbcL gene (for a subset of taxa) and a combined data set were carried out. All trees had a strongly supported clade consisting of all Ulva, Enteromorpha and Chloropelta species, but Ulva and Enteromorpha were not monophyletic. The recent removal of Umbraulva olivascens (P.J.L. Dangeard) Bae et I.K. Lee from Ulva is supported, although the relationship of the segregate genus Umbraulva to Ulvaria requires further investigation. These results, combined with earlier molecular and culture data, provide strong evidence that Ulva, Enteromorpha and Chloropelta are not distinct evolutionary entities and should not be recognized as separate genera. A comparison of traits for surveyed species revealed few synapomorphies. Because Ulva is the oldest name, Enteromorpha and Chloropelta are here reduced to synonymy with Ulva, and new combinations are made where necessary