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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 nerve-sparing 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.

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 PubMed®, Embase®, 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.

Testicular cancer is the most common malignancy among men between 14 and 44 years of age, and its incidence has risen over the past two decades in Western countries. Both genetic and environmental factors contribute to the development of testicular cancer, for which cryptorchidism is the most common risk factor. Progress has been made in our understanding of the disease since the initial description of carcinoma in situ of the testis in 1972 (now referred to as germ cell neoplasia in situ), which has led to improved treatment options. The combination of surgery and cisplatin-based chemotherapy has resulted in a cure rate of >90% in patients with testicular cancer, although some patients become refractory to chemotherapy or have a late relapse; an improved understanding of the molecular determinants underlying tumour sensitivity and resistance may lead to the development of novel therapies for these patients. This Primer provides an overview of the biology, epidemiology, diagnosis and current treatment guidelines for testicular cancer, with a focus on germ cell tumours. We also outline areas for future research and what to expect in the next decade for testicular cancer.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 32-year-old man with a history of a mixed germ cell tumor of the testis presented with acute-onset, right-sided weakness and numbness. His previous treatment included orchiectomy, which revealed a 5-cm tumor that was 95% yolk sac tumor and 5% embryonal carcinoma, and retroperitoneal lymph node dissection for clinical stage I disease in January 2010, which revealed no nodal metastases. Starting in June 2010, he was treated with four cycles of etoposide and cisplatin for pulmonary and thoracic lymph node metastases and a rising serum alpha-fetoprotein (AFP) level. He subsequently received four cycles of paclitaxel, ifosfamide, and cisplatin for relapse in the lungs and mediastinal nodes with a rising AFP level starting in January 2011. He reported having a 2-week history of intermittent headaches in December 2011, when he presented with acute-onset, right-sided weakness and numbness. Computed tomographs of the head was obtained and demonstrated a left parietal intracranial hemorrhage without midline shift or hydrocephalus. Brain magnetic resonance imaging (MRI) showed a complex, 4.5-cm mass consistent with a hemorrhagic metastasis. His serum AFP level was elevated at 47 ng/mL. The patient became progressively obtunded and underwent emergency surgical decompression and resection of the tumor. Histopathologic evaluation of the resected tissue showed metastatic germ cell tumor predominantly consisting of a yolk sac element (Fig 1). His AFP level declined rapidly after resection, and computed tomography of the chest, abdomen, and pelvis showed no evidence of metastatic disease. However, 2 weeks later, his AFP level rose again, and repeat MRI of the brain showed a 3-cm mass in the left mesial parietal lobe adjacent to the resection site. He started treatment with filgrastim to facilitate collection of circulating hematopoietic stem cells. Several days later, after apheresis, he received his first of two cycles of high-dose carboplatin 700 mg/m(2) on days -5, -4, and -3 and etoposide 750 mg/m(2) on days -5, -4, and -3. The patient had a complete response to high-dose chemotherapy and no major acute complications. His cancer remains in complete remission 3 years later without additional treatment. His three lines of chemotherapy left him with chronic peripheral neuropathy., (© 2015 by American Society of Clinical Oncology.)

Background: As the most common cancer among males in late adolescence and early adulthood and as a disease with a 5-year relative survival rate of 96%, testis cancer has many survivors who live many years during which chronic toxicities may impair their quality of life., Methods: In this review, I aimed to summarize the most relevant literature on quality of life among testis cancer survivors identified via PubMed literature search between 1990 and 2015., Results: Survivors of testis cancer experience an overall quality of life (QOL) that is not measurably different from that of men of the same age in the general population. Nonetheless, testis cancer and its treatments can result in a variety of long-term conditions that affect QOL. These include peripheral neuropathy, hearing loss, tinnitus, fatigue, and Raynaud-like phenomenon. Exercise interventions have been shown to improve fatigue and overall QOL in cancer survivors, and there is evidence that psychosocial and mind-body interventions may also be beneficial. Pharmacological interventions have not been shown to be helpful for cancer-related fatigue, hearing loss, or neuropathy., Conclusions: Testis cancer survivors should be asked about symptoms related to the conditions above and referred to specialists as indicated. Survivors complaining of fatigue should be encouraged to adopt a regular program of aerobic exercise., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Testicular cancer (TC) is the most common neoplasm in males aged 15-40 years. The majority of patients have no evidence of metastases at diagnosis and thus have clinical stage I (CSI) disease [Oldenburg J, Fossa SD, Nuver J et al. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi125-vi132; de Wit R, Fizazi K. Controversies in the management of clinical stage I testis cancer. J Clin Oncol 2006; 24: 5482-5492.]. Management of CSI TC is controversial and options include surveillance and active treatment. Different forms of adjuvant therapy exist, including either one or two cycles of carboplatin chemotherapy or radiotherapy for seminoma and either one or two cycles of cisplatin-based chemotherapy or retroperitoneal lymph node dissection for non-seminoma. Long-term disease-specific survival is ∼99% with any of these approaches, including surveillance. While surveillance allows most patients to avoid additional treatment, adjuvant therapy markedly lowers the relapse rate. Weighing the net benefits of surveillance against those of adjuvant treatment depends on prioritizing competing aims such as avoiding unnecessary treatment, avoiding more burdensome treatment with salvage chemotherapy and minimizing the anxiety, stress and life disruption associated with relapse. Unbiased information about the advantages and disadvantages of surveillance and adjuvant treatment is a prerequisite for informed consent by the patient. In a clinical scenario like CSI TC, where different disease-management options produce indistinguishable long-term survival rates, patient values, priorities and preferences should be taken into account. In this review, we provide an overview about risk factors for relapse, potential benefits and harms of adjuvant chemotherapy and active surveillance and a rationale for involving patients in individualized decision making about their treatment rather than adopting a uniform recommendation for all., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The treatment of patients with Stage I-II seminoma has changed considerably in the past decade, and in November 2009, an International Consensus meeting was held under the sponsorship of the Union for International Cancer Control (UICC), Société Internationale d'Urologie (SIU), and International Consultation on Urological Diseases (ICUD) to review recent updates in the published data and develop international consensus guidelines on the treatment of this group of patients. In Stage I disease, the consensus conference recommended that patients should be informed of all treatment options, including the potential benefits and side effects of each treatment. It was agreed that this discussion should include a review of the possible salvage treatment effects. In addition, in patients willing and able to adhere to a surveillance program, this should be considered the management option of choice (assuming facilities are available for suitable monitoring). For Stage IIA disease, the consensus conference recommended that radiotherapy should be considered the standard treatment in the absence of contraindications. For Stage IIB disease, chemotherapy or radiotherapy were considered reasonable treatment approaches, and for Stage IIC disease, chemotherapy should be considered the standard treatment approach. For patients with a residual mass after chemotherapy, the consensus conference noted that patients with masses <3 cm in diameter could likely be safely observed, and patients with residual masses >3 cm in diameter could be considered for immediate surgery or close observation. It was also noted that surgery in this setting is technically challenging and could be associated with greater morbidity than in patients with nonseminomatous tumors., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Because of a rising incidence of, and declining mortality from, testicular cancer, there are an increasing number of survivors of testicular cancer. Given their young age at diagnosis, the survivors have many years of life ahead of them during which they may experience adverse consequences from cancer and its treatment. Over the past few decades and particularly in this century, research into the short- and long-term effects of treatments of testicular cancer has grown rapidly, and now there exist a much greater body of data to help us counsel patients about the risks and side effects of these treatments., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The optimal management of clinical stage I testicular germ cell tumors remains controversial despite a cure rate of 99%. Alternatives for stage I nonseminomas include close surveillance, retroperitoneal lymph node dissection, and chemotherapy. For pure seminomas, the options are surveillance, chemotherapy, and radiation. Understanding the pros and cons of each approach may help in choosing a management plan.

Testis cancer is rare and rapidly progressive but can almost always be cured. Early detection and prompt treatment by an experienced clinician are the cornerstones of successful management. A delay in diagnosis and inadequate or inappropriate treatment increase the risk of death. The author reviews risk factors, diagnostic features, and current treatment.

The optimal management of patients who have clinical stage I nonseminomatous germ cell tumors remains controversial. Surveillance, retroperitoneal lymph node dissection (RPLND), and chemotherapy with two cycles of bleomycin-etoposide-cisplatin are established treatment options and all are associated with long-term cancer control rates of 97% or greater. Studies have consistently identified the presence of lymphovascular invasion and a predominant component of embryonal carcinoma in the primary tumor as risk factors for occult metastatic disease in these patients. Patients who do not have these risk factors are optimally managed by active surveillance given the low risk for relapse. For patients at high risk for relapse and who are not candidates for surveillance, we believe the evidence supports RPLND over primary chemotherapy.

Stage I and II testicular germ cell tumors (GCTs) are almost always cured with appropriate treatment and most ongoing research regarding these tumors focuses on minimizing treatment toxicity. The management of clinical stage I testicular GCTs has grown more complicated due to the emergence of a brief course of chemotherapy as an additional treatment option for stage I seminomas and stage I nonseminomas. In addition, growing concern about radiation-induced cancers and other late toxicity has dulled enthusiasm for radiotherapy as a treatment for stage I seminomas. However, recent randomized trials have shown that radiotherapy doses and field sizes can be lowered without compromising cure rates and it is possible that this reduction in radiation exposure will reduce the rate of secondary cancers. At this point in history, stage I patients have three treatment options following radical orchiectomy: adjuvant (sometimes called "primary") chemotherapy (carboplatin for seminomas and the combined regimen of bleomycin, etoposide, and cisplatin for nonseminomas), surveillance, and either retroperitoneal lymph node dissection (for nonseminomas) or radiotherapy (for pure seminomas). Clinical studies have made it possible to identify subgroups of patients at high and low risk for relapse and this has made it possible to tailor treatment decisions to the individual patient's postorchiectomy relapse risk.