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Advanced germ cell cancer can be cured in most patients using chemotherapy with or without surgery. A small fraction of patients with nonseminomatous tumors (NSGCT) and an even smaller percentage of seminoma patients are destined to have a less favorable outcome, due to an inadequate response to first-line chemotherapy (failure to achieve remission, finding of residual viable carcinoma at post-chemotherapy surgery, or relapse after achieving a remission). Despite the apparent salvage potential for regimens containing ifosfamide or paclitaxel, no proof exists that such combinations are superior to the standard regimen of four cycles of cisplatin, etoposide, and bleomycin (PEB) in the front-line therapy of patients with advanced NSGCT. Other modifications of first-line therapy, such as the addition of paclitaxel or the use of escalated doses of cisplatin, also have failed to increase the cure rate. The use of single or tandem cycles of high-dose chemotherapy (HDT with autologous hematopoietic cell transplant [aHCT]) in various settings (for selected patients with poor prognostic features before therapy, patients predicted to have a poor outcome based on the rate of serum tumor marker decline while on therapy, and patients in relapse or failure to achieve adequate response to standard therapy) has been evaluated in many phase II and a limited number of phase III trials, which are summarized in this review. Important questions that remain to be answered include the role of new agents and the use of more sophisticated techniques to understand prognostic and predictive factors in selecting therapy for GCT.

Testicular cancer is the most common cancer in men aged 15 to 40 years in the United States, Canada, and many European countries. Given the excellent prognosis of most men with testicular cancer, updates in care after treatment have become very important. This article provides a review of the available evidence, integrated with expert medical judgment, in the area of testicular cancer follow-up.

The outcome of patients with metastatic renal cell carcinoma has been substantially improved with administration of the currently available molecularly targeted therapies. However, proper selection of therapy and management of toxicities remain challenging. NCCN convened a multidisciplinary task force panel to address the clinical issues associated with these therapies in attempt to help practicing oncologists optimize patient outcomes. This report summarizes the background data presented at the task force meeting and the ensuing discussion.

These NCCN Guidelines Insights highlight treatment recommendations and updates specific to the management of patients with advanced non-clear cell carcinoma included in the 2014 version of the NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer.

Over the past few years, the NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways for treatment of microscopic satellitosis (added in v2.2020), and the following Principles sections: Molecular Testing (added in v2.2019), Systemic Therapy Considerations (added in v2.2020), and Brain Metastases Management (added in v3.2020). The v1.2021 update included additional modifications of these sections and notable revisions to Principles of: Pathology, Surgical Margins for Wide Excision of Primary Melanoma, Sentinel Lymph Node Biopsy, Completion/Therapeutic Lymph Node Dissection, and Radiation Therapy. These NCCN Guidelines Insights discuss the important changes to pathology and surgery recommendations, as well as additions to systemic therapy options for patients with advanced disease.

The NCCN Guidelines for Uveal Melanoma include recommendations for staging, treatment, and follow-up of patients diagnosed with uveal melanoma of the choroid or ciliary body. In addition, because distinguishing between uveal melanoma and benign uveal nevi is in some cases difficult, these guidelines also contain recommendations for workup of patients with suspicious pigmented uveal lesions, to clarify the tests needed to distinguish between those who should have further workup and treatment for uveal melanoma versus those with uncertain diagnosis and low risk who should to be followed and later reevaluated. These NCCN Guidelines Insights describe recommendations for treatment of newly diagnosed nonmetastatic uveal melanoma in patients who have already undergone a complete workup.