Testicular cancer is relatively uncommon and accounts for ,1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nervesparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with .50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.

BackgroundThe delivery of DNA into human cells has been the basis of advances in the understanding of gene function and the development of genetic therapies. Numerous chemical and physical approaches have been used to deliver the DNA, but their efficacy has been variable and is highly dependent on the cell type to be transfected.ResultsStudies were undertaken to evaluate and compare the transfection efficacy of several chemical reagents to that of the electroporation/nucleofection system using both adherent cells (primary and transformed airway epithelial cells and primary fibroblasts as well as embryonic stem cells) and cells in suspension (primary hematopoietic stem/progenitor cells and lymphoblasts). With the exception of HEK 293 cell transfection, nucleofection proved to be less toxic and more efficient at effectively delivering DNA into the cells as determined by cell proliferation and GFP expression, respectively. Lipofectamine and nucleofection of HEK 293 were essentially equivalent in terms of toxicity and efficiency. Transient transfection efficiency in all the cell systems ranged from 40%-90%, with minimal toxicity and no apparent species specificity. Differences in efficiency and toxicity were cell type/system specific.ConclusionsIn general, the Amaxa electroporation/nucleofection system appears superior to other chemical systems. However, there are cell-type and species specific differences that need to be evaluated empirically to optimize the conditions for transfection efficiency and cell survival.

PURPOSE To provide recommendations for the management of patients with metastatic clear cell renal cell carcinoma (ccRCC). METHODS An Expert Panel conducted a systematic literature review to obtain evidence to guide treatment recommendations. RESULTS The panel considered peer-reviewed reports published in English. RECOMMENDATIONS The diagnosis of metastatic ccRCC should be made using tissue biopsy of the primary tumor or a metastatic site with the inclusion of markers and/or stains to support the diagnosis. The International Metastatic RCC Database Consortium risk criteria should be used to inform treatment. Cytoreductive nephrectomy may be offered to select patients with kidney-in-place and favorable- or intermediate-risk disease. For those who have already had a nephrectomy, an initial period of active surveillance may be offered if they are asymptomatic with a low burden of disease. Patients with favorable-risk disease who need systemic therapy may be offered an immune checkpoint inhibitor (ICI) in combination with a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI); patients with intermediate or poor risk should be offered a doublet regimen (no recommendation was provided between ICIs or an ICI in combination with a VEGFR TKI). For select patients, monotherapy with either an ICI or a VEGFR TKI may be offered on the basis of comorbidities. Interleukin-2 remains an option, although selection criteria could not be identified. Recommendations are also provided for second- and subsequent-line therapy as well as the treatment of bone metastases, brain metastases, or the presence of sarcomatoid features. Participation in clinical trials is highly encouraged for patients with metastatic ccRCC. Additional information is available at www.asco.org/genitourinary-cancer-guidelines

PURPOSE Nearly all men with prostate cancer treated with androgen receptor (AR) signaling inhibitors (ARSIs) develop resistance via diverse mechanisms including constitutive activation of the AR pathway, driven by AR genomic structural alterations, expression of AR splice variants (AR-Vs), or loss of AR dependence and lineage plasticity termed neuroendocrine prostate cancer. Understanding these de novo acquired ARSI resistance mechanisms is critical for optimizing therapy. MATERIALS AND METHODS A novel liquid biopsy technology was used to collect mRNA from circulating tumor cells (CTCs) to measure expression of AR-Vs, AR targets, and neuroendocrine prostate cancer markers. An institutional review board–approved prospective cohort (N = 99) was used to identify patterns of gene expression. Two prospective multicenter phase II clinical trials of ARSIs for men with castration-resistant prostate cancer (ClinicalTrials.gov: NCT01942837 [enzalutamide, N = 21] and NCT02025010 [abiraterone, N = 27]) were used to further validate these findings. RESULTS Hierarchical clustering of CTC transcripts identified two distinct clusters. Cluster 2 (C2) exhibited increased expression of AR-regulated genes and was associated with worse overall survival (median 8.6 v 22.4 months; P < .01; hazard ratio [HR] = 3.45 [1.9 to 6.14]). In multivariable analysis, C2 was prognostic independent of other clinicopathologic variables. AR-V status was not significant when accounting for C2. Upon further validation in pooled multicenter phase II trials, C2 was associated with worse overall survival (15.2 months v not reached; P < .01; HR = 8.43 [2.74 to 25.92]), prostate-specific antigen progression-free survival (3.6 v 12 months; P < .01; HR = 4.64 [1.53 to 14.11]), and radiographic progression-free survival (2.7 v 40.6 months; P < .01; HR = 4.64 [1.82 to 17.41]). CONCLUSION We demonstrate that a transcriptional profile detectable in CTCs obtained from liquid biopsies can serve as an independent prognostic marker beyond AR-V7 in patients with metastatic prostate cancer and can be used to identify the emergence of multiple ARSI resistance mechanisms. This is currently being investigated in additional prospective trials.