A variety of nongerm cell histologies, including sarcoma, adenocarcinoma, primitive neuroectodermal tumor and leukemia, may occur in association with germ cell tumor. Chromosomal abnormalities in these tumors include i (12p), reflecting germ cell tumor clonality, as well as chromosomal abnormalities associated with the transformed histology. These tumors do not respond like germ cell tumor to cisplatin-containing chemotherapy regimens. Treatment should be tailored according to that used in standard management of the transformed histology, and surgical resection is the mainstay of therapy.

Purpose: Testis cancer is the most common solid malignancy in young males. The purpose of this guideline is to provide a useful reference on the effective evidence-based treatment of early stage testicular cancer. Methods: The systematic review utilized to inform this guideline was conducted by a methodology team at the Johns Hopkins University Evidence-based Practice Center. The methodology team searched using PubMedÒ, EmbaseÒ, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1980 through August 2018. The evidence review team also reviewed relevant systematic reviews and references provided by the panel to identify articles that may have been missed by the database searches. Results: When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low). Such evidence-based statements are provided as Strong, Moderate, or Conditional Recommendations. In instances of insufficient evidence, additional guidance is provided as Clinical Principles and Expert Opinions. Conclusions: This guideline attempts to improve a clinician's ability to evaluate and treat patients with testicular cancer, but higher quality evidence in future trials will be essential to improve level of care for these patients.

ESTICULAR CANCER IS THE MOST common cancer diagnosis in men between the ages of 15 and 35 years, with approximately 8000 cases detected in the United States annually. 1 The majority (95%) of testicular neoplasms are germ cell tumors (GCTs), with other testicular neoplasms (ie, sex-cord stromal tumors, lymphomas) occurring more rarely. Germ cell tumors may also arise in extragonadal locations, such as the mediastinum and retroperitoneum.Remarkable progress has been made in the medical treatment of advanced testicular cancer with a substantial increase in cure rates from approximately 25% in the mid-1970s to nearly 80% today. 2 This cure rate is the highest of any solid tumor and improved survival is primarily due to effective chemotherapy. 3 It is important for all physicians to be familiar with this malignancy, because patients may initially present to a variety of practitioners, and delays in therapy are associated with more extensive disease resulting in more intensive treatment and lower cure rates. 4 In addition, the immediate and longterm toxic effects of treatment often require management from physicians of various disciplines. This article reviews the current evidence-based treatments for advanced testicular GCT, and the acute and chronic toxic effects that may result. The management of early stage (I-IIA) testicular cancers has been reviewed elsewhere. [5][6][7] BACKGROUND GCT Histology and GeneticsGerm cell tumors are malignancies of primordial germ cells, the cells destined to become spermatozoa. With neoplastic transformation, these cells take on a variety of histologies, reflect-See also Patient Page. CME available online at www.jamaarchivescme.com and questions on p 706.

Large prospective studies are needed to confirm these results and to evaluate nuclear overexpression of p53 protein as a prognostic marker in bladder cancer.

Four cycles of TIP as second-line therapy achieved a durable CR rate in a high proportion of patients with relapsed testicular GCT. The high CR rate emphasizes the importance of patient selection according to prognostic factors to achieve a favorable outcome to conventional-dose salvage therapy.