Key Questions

KEY QUESTIONS INVOLVING THE DIAGNOSIS AND INITIAL MANAGEMENT OF TESTICULAR CANCER: i.After a suspicious physical or self-examination, what is the diagnostic accuracy (sensitivity, specificity, positive and negative predictive values, likelihood ratios, area under the ROC curve or diagnostic odds ratio) of magnetic resonance imaging (MRI) of the scrotum and testis and scrotal ultrasound to diagnose stage IA, IB and IIA primary testicular seminoma and non-seminomatous germ cell tumor (NSGCT) respectively?

a.Should an MRI of the scrotum and testis be performed prior to orchidectomy to evaluate an indeterminate testicular mass?

ii.In what context should the following tests be offered during staging of IA, IB and IIA seminoma and NSGCT?

a.Chest x-ray or Chest CT b.CT or MRI of the abdomen and pelvis

c.Bone scan d.Assessment of fertility (total testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), semen analysis)

iii.What is the optimal local surgical therapy for a man with a suspicious testicular mass that is associated with good oncologic outcomes? a.The role of radical inguinal orchidectomy b.The role of testis-sparing/partial orchidectomy c.The role of routine contralateral testis biopsy

iv.To whom and when should testicular prosthesis and sperm banking be offered?

KEY QUESTIONS REGARDING COMPARATIVE EFFICACY OF MANAGEMENT STRATEGIES FOR EARLY-STAGE TESTICULAR CANCER: v.Among men with Stage IA and IB NSGCT, what is the relative effectiveness of active surveillance vs. RPLND vs. chemotherapy on

a.oncologic outcomes b.short and long term morbidity c.quality of life

vi.Among men with Stage IIA NSGCT, what is the relative effectiveness of RPLND vs. chemotherapy on

a.oncologic outcomes b.short and long term morbidity c.quality of life

vii.Among men with stage IA and IB seminoma, what is the relative effectiveness of active surveillance vs. radiation vs. chemotherapy on

a.oncologic outcomes b.short and long term morbidity c.quality of life

viii.Among men with stage IIA seminoma, what is the relative effectiveness of radiation vs. chemotherapy on

a.oncologic outcomes b.short and long term morbidity c.quality of life

ix.For men with stage IA and IB seminoma or NSGCT who elect active surveillance, what is the efficacy and comparative efficacy of existing active surveillance protocols? (i.e. is there an optimal active surveillance regimen)

x.For men with stage IA, IB and IIA seminoma or NSGCT, what is the efficacy and comparative efficacy of existing survivorship surveillance protocols? (i.e. what is the optimal post-treatment surveillance strategy to improve survival, early detection of relapses and quality of life?)

Relevant patients

i.Adolescent and adult males with previously untreated stage I testicular cancer of germ cell origin

The National Cancer Institute estimates that there will be 8,720 new testicular cancer cases in the United States in 2016, more than 95% of which will likely be of germ cell origin.1 The vast majority ( 90%) of these cases will be in post-pubertal young males between the ages of 15 and 35 years.1,2 Two distinct variants of testicular germ cell tumors (GCT) exist and they include seminomas, which makes up approximately half of all testicular GCT, and non-seminomatous germ cell tumor (NSGCT) which makes up the other half, and includes mixed seminomas.2 Approximately 75% of new cases are diagnosed in the early stages of the disease process when the tumor is still confined to the testis and has not shown any evidence of regional or distant metastasis.3 This topic nomination is going to be focused only on patients that are being worked up for and newly diagnosed with localized seminoma and NSGCT (stages IA, IB and IIA).

Relevant subpopulations

i.Young men aged between 13

40 years

ii.Normalized serum tumor markers post-orchidectomy

Health-related benefits

i.Improved consistency of diagnostic testing and management among providers ii.Improved early detection rates iii.Reduced relapse rates iv.Improved overall survival

v.Improved quality of life vi.Improved patient-reported outcomes (sexual, relational, emotional health)

Health-related harms, risks, side effects

i.Tumor persistence ii.Risk of under-diagnosis iii.Risk of over-staging or over-treatment iv.Early and late treatment morbidity (neurotoxicity, nephrotoxicity, cardiovascular events, pulmonary toxicity, androgen deficiency and secondary malignancies)

References: 1.SEER Cancer Statistics Factsheets: testis Cancer. National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/statfacts/html/testis.html 2.Campbell, Meredith F, Wein, Alan J. Kavoussi, Louis R. (Eds) (2016) Campbell-Walsh Urology (11th ed)/ editor-in-chief, Alan J. Wein; Stephenson AJ, Gilligan TD. Neoplasms of the Testis. 34: 784-814.

3.McGlynn KA, Devesa SS, Graubard BI, Castle PE. Increasing incidence of testicular germ cell tumors among black men in the United States. JCO. 2005; 23(24): 5757-5761.

Primary testicular cancer is the most common cancer among young men in many industrialized countries, including the United States.1 Over the past five decades, its age-adjusted incidence has increased from 2.9 per 100,000 in 19752 to 5.7 per 100,000 in 2013.1 Despite this increase, fatality rates have decreased considerably over time and testicular cancer is now one of the models for curable cancer.1 However, treatment success relies heavily on early detection and prompt, appropriate multidisciplinary care, which can be a complex act in a complex health system.

Advancements in treatment strategies over the years, particularly cisplatin-based chemotherapy and integrative surgery, have resulted in excellent overall survival rates regardless of stage at diagnosis, but the obvious step-wise decrease in survival odds cannot be ignored. When localized and confined to the testis, there is a 99.3% 5-year relative survival, but once regional spread has occurred, 5-year survival drops to 96.1%. If distant metastasis is present, only 75% of patients live to the 5-year mark.1

In addition, given the oncologic successes, testicular cancer can be considered a disease of survivors

with nearly 250,000 estimated survivors currently living in the US.1 Given the relatively young age at diagnosis and high curability, these men represent a unique population subject to long-term side effects and survivorship issues related to curative treatments that are not considered in other malignancies, which are more commonly represented by elderly, comorbid patients.

Treatment complexity and the presence of controversial treatment protocols contribute to the presence of variations in care that could greatly influence treatment and outcome inequalities. A recent study by Wymer et al reported a disturbing 27% of patients with stage I testicular cancer receiving non-guideline directed care (NGDC) across three large academic centers in the United States.3 Overtreatment and inappropriate imaging were the two most common causes of NGDC. In addition, a striking 11% of the 177 patients who received NGDC also experienced a delay to diagnosis, which is known to lead to poorer treatment outcomes.3

Several organizations have published testicular cancer guidelines, such as the National Comprehensive Cancer Network (NCCN)4 which was the basis by which the Wymer study was conducted, as well as the European Association of Urology (EAU).5 However, both of these guidelines have an expansive scope covering all stages of the disease process. The management of advanced testicular cancer is completed through chemotherapy and there are minimal, if any controversies regarding regimen and timing which have been addressed in a number of randomized, controlled trials. These existing guidelines thus provide more comprehensive guidance on the management of advanced testicular cancer but fail to provide sufficient focus on early stage disease, which is more prevalent, and may have more controversial aspects of care where more detailed guidance will be helpful to the providers. The AUA s goal is to develop a single, comprehensive guidance document for early-stage testicular cancer that is focused on which tests to use to accurately stage the cancer, which treatment protocols to choose from which would confer patients with the best outcomes whilst minimizing harm, and how best to surveil and address survivorship aspects of care, that are pertinent to maintain a man s sexual, emotional, relational and overall well-being.

References: 1.SEER Cancer Statistics Factsheets: testis Cancer. National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/statfacts/html/testis.html 2.Holmes L Jr, Escalante C, Garrison O, et al. Testicular Cancer Incidence Trends in the United States (1975-2004): Plateau or shifting racial paradigm? Public Health. 2008; 122(9): 862-872. 3.Wymer KM, Pearce SM, Harris KT, et al. Adherence to National Comprehensive Cancer Network Guidelines for Testicular Cancer. J Urology. 2016 [In press] 4.NCCN Clinical Practice Guidelines in Oncology. Testicular Cancer. 2015. https://www.tri-kobe.org/nccn/guideline/urological/english/testicular.pdf 5.European Association of Urology. Guidelines on Testicular Cancer. 2015. http://uroweb.org/wp-content/uploads/11-Testicular-Cancer_LR1.pdf

This evidence report produced by AHRQ that will be very focused only on localized, early stage testicular GCT, which forms the greatest proportion of all testicular cancers and has the greatest potential for cure, will form the foundation with which the AUA will use to develop a comprehensive evidence-based clinical guideline on how best to approach the work-up/diagnosis, treatment and post-treatment surveillance and survivorship aspects of care. This guideline can be produced in a relatively short time-frame given that the data collection, review and synthesis of the evidence report would have already been performed by AHRQ using the highest quality standards of a systematic review. Following publication of the full guideline on the AUA website, the executive summary will be published in manuscript form in the Journal of Urology, the official journal of the AUA with extensive readership spanning both national and international clinical communities. This model has worked extremely well, for example, with the recently updated AUA guideline on the Management of Clinically Localized Kidney Cancer. The comprehensive systematic review produced by the AHRQ-selected Evidence-Based Practice Center (EPC) served as the evidence base for the guideline update, which is in the process of finalization through the AUA. The AUA and its panel of experts were impressed with the quality of report and ease at which the evidence transitioned into guideline statements for its readership and beyond. The proposed testicular cancer evidence report would similarly serve as the evidence base for a new guideline publication from the AUA.

Upon publication of the guideline, the AUA will disseminate information about the guideline through its annual meeting, the AUA Health Policy Brief, AUA News and through its Board of Directors and members. The AUA Guidelines Department also works closely with the AUA Foundation, committed to patient education and advocacy, to develop patient guides from its clinical practice guidelines. The AUA will also disseminate pocket guides to both urologic specialists and primary care physicians in easy-to-access formats. The development of a focused clinical practice guideline on early stage testicular cancer would also enable the AUA to develop materials with a strong focus on patient counseling and education, which is essential to promote shared decision-making when discussing treatment options. The AUA concurrently works with health informatics specialists to make guideline statements more actionable and relevant for electronic health records (EHRs). Thus, the creation of an AHRQ evidence report on early stage testicular cancer will enable the AUA to continue its tradition of providing quality; evidence-based education and guidance to various stakeholders involved with the care of patients with testicular cancer.

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Professional Society

If you are you making a suggestion on behalf of an organization, please state the name of the organization

American Urological Association

Please tell us how you heard about the Effective Health Care Program

The AUA has previously partnered with AHRQ via the Effective Health Care Program in the development of evidence reports on the Management of Female Overactive Bladder (OAB), Medical Management of Recurrent Nephrolithiasis, Cryptorchidism, Renal Mass and Bladder Cancer. Following the publication of each of these guidelines, the AUA was able to carry out extensive dissemination efforts that included the production of high-quality videos for the purposes of continuing medical education (CME), patient and medical provider trifolds, Clinical Problem Solving Protocols, and a compendium of all AUA guidelines in both an App and in a Pocket-Guide format. Using the AHRQ-produced evidence report on early stage testicular cancer, the AUA is prepared to continue such efforts with the aim of providing carefully synthesized knowledge and guidance in easily accessible formats to reduce practice variations and improve health outcomes for all patients.