Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

Question: What is the etiology of cryptorchidism? What are the environmental factors (maternal smoking, maternal diabetes mellitus etc.) that may contribute to the development of this condition?

Question: What is the ideal diagnostic workup for accurate identification of cryptorchidism? What are the relative benefits of imaging vs. laparoscopy in determining the location of the cryptorchid testis? Question: What are the relative benefits of the various treatment interventions (surgical vs. hormonal, early vs. late orchiopexy, different surgical techniques) for this condition, particularly with regard to infertility/sub-fertility, and the risk of development of testicular malignancy??

Question: How does the form of cryptorchidism (unilateral vs. bilateral, palpable vs. non-palpable, anatomic location) and the occurrence of associated abnormalities (hernia, hypospadias etc.) impact treatment and outcomes? Question: What are the complications associated with the various treatment alternatives?

Question: What is the appropriate follow-up care for patients treated for cryptorchidism? For those in whom the condition is observed but not treated? Question: What information must be conveyed to the patient’s parents or guardians during counseling to enable them to make an informed decision about their child’s treatment?

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

• Imaging techniques vs. laparoscopy for localization of testis
• Hormonal vs. surgical vs. combination (hormonal+ surgical) treatments
• Early vs. late orchiopexy, various surgical techniques

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

• The question applies to the male neonate/pediatric population, and is the most common congenital defect found in male neonates (Kojima, Mizuno, Kohri, & Hayashi, 2009).
• Significant comorbidities include hypospadias and hernia (patent processus vaginalis), among others.
• Therapy, either surgical or medical (hormonal), is generally recommended if symptoms do not resolve within the first 6-12 months after birth (Gapany et al., 2008).

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

• There are a wide range of presentations of the disease: cryptorchidism may be unilateral or bilateral; palpable or non palpable, and may vary by anatomic location. Indication for therapy may vary by presentation.
• Concurrence of hypospadias or ambiguous genitalia with bilateral non-palpable testes may represent more severe developmental abnormalities that can be life threatening and may indicate specific testing/treatment (Wein, 2007). Bilateral non-palpable testes, even in the absence of hypospadias, is an important predictor of an intersex state and may also require specific testing/treatment (Kaefer et al., 1999).
• Cryptorchidism has been found to be more common among Asians, and delayed testicular descent has been correlated with ethnicity as well, being more common among Hispanics and Blacks (Berkowitz & Lapinski, 1996). In addition, some evidence suggests that black and mixed-race men with cryptorchidism are more likely to develop testicular cancer than white patients with the condition (Abratt, Reddi, & Sarembock, 1992).

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

Cryptorchidism carries an inherent psychological and emotional burden, in addition to being associated with both infertility and testicular malignancy. Timely treatment may be able to prevent these problems.

• It is commonly believed that ‘early surgical repositioning of the testis into the scrotum before the onset of histopathological changes can reduce the risk of subfertility’ (Thorup & Cortes, 2009; Wein, 2007).
• Evidence suggests that prepubertal orchiopexy could reduce or eliminate the increased risk of testicular cancer (Thorup & Cortes, 2009; Thorup et al., 2007; Walsh, Dall'Era, Croughan, Carroll, & Turek, 2007).
• Establishing the best methods for diagnosis and treatment of cryptorchidism and associated defects would be beneficial, and in some cases life-saving, for patients that suffer from cryptorchidism and associated conditions such as hypospadias, hernia, testicular torsion, ambiguous genitalia etc.

Describe any health-related risks, side effects, or harms that you are concerned about.

• Risk of radiation exposure from diagnostic imaging (CT).
• Risks of orchiopexy may include damage to the vas deferens, bleeding, and infection. There is a small chance of testicular atrophy, or that the testicle/s will retract following surgery, and additional treatment may be necessary (Elyas et al., 2010).
• Side effects of hormone therapy may include enlargement of penis and/or testicles, growth of genital hair and aggression (Mathers, Sperling, Rubben, & Roth, 2009). In addition, success of human chorionic gonadotropin (hCG) has varied widely in different studies and needs to be reviewed systematically.

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

• Cancer
• Depression and other mental health disorders
• Developmental delays, attention-deficit hyperactivity disorder, and autism
• Pregnancy, including preterm birth

AHRQ Priority Populations

• Low income groups
• Minority groups
• Children

Federal Health Care Program

• Medicaid
• State Children's Health Insurance Program (SCHIP)

Importance

Describe why this topic is important.

Cryptorchidism, also known as undescended testicle, has been estimated to affect over 3% of full-term newborns as well as up to 30% of premature infants making it the most common genital problem encountered in pediatrics (Barthold & Gonzalez, 2003). Although about 70% of the cryptorchid testes spontaneously descend within the first year, the rate of boys that continue to suffer from the condition remains

more or less constant at approximately 1% (Berkowitz et al., 1993; Ritzen & Kollin, 2009).

It has been estimated that there were over 600,000 (96 per 100,000) physician office visits with cryptorchidism as the primary diagnosis between 1992 and 2000 and a constant annualized rate of orchiopexy of 18 per 100,000 in 1994 to 1996 (Miller, Saigal, & Litwin, 2009; Pohl, Joyce, Wise, & Cilento, 2007). Given that the average submitted charges in 2008 for a level 3 in-office exam was $146 for new patients and $87 for established patients according to CMS physician payment information for value driven healthcare data, and the cost of infant and postpubertal orchiopexy has been estimated to be $7500 and $10,928 respectively (Hsieh, Roth, & Meng, 2009), this condition incurs direct costs of millions of dollars annually, even by the most modest estimates.

Cryptorchidism is, therefore, both a significant and costly health problem in the United States. It may be the most common congenital abnormality in male neonates and is certainly considered the most common genital abnormality in males.

It is widely accepted that cryptorchidism is associated with subfertility or infertility. Campbell’s Urology considers it a tenet of treatment that ‘early surgical repositioning of the testis into the scrotum before the onset of histopathological changes can reduce the risk of subfertility’. The validity of this claim is still debated by some, and could be examined by conducting an evidence review.

It is has been clearly established that there is a strong positive correlation bet

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

The AUA intends to produce a clinical practice guideline on cryptorchidism in late 2011 or in 2012 from an AHRQ evidence report if the topic is accepted. AUA has previous experience in partnering with AHRQ on the Treatment of Overactive Bladder in Women, which is currently being developed into a guideline by AUA. The organization also looks forward to beginning work on the Medical Management of Stones Guideline which will be developed from the evidence report that AHRQ will soon develop, based on a previous topic submission by the AUA.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

• Cryptorchidism is not simply a single disease process but a collection of clinical abnormalities with varied causes. This makes it difficult to classify, and there are considerable variations in presentation and treatment of the condition.
• The inherent diversity of cryptorchidism has led to controversy and uncertainty in the means identification and treatment of the condition. Among the common variations of cryptorchidism are differences in the anatomic position of the testes, unilateral and bilateral cryptorchidism, structural and hormonal abnormalities, and association with other conditions such as hernia and hypospadias. Classification of cryptorchidism by anatomical position is often difficult, and although there are a number of classification systems the most popular is simply palpable (80%) vs. non palpable (20%). Accurate classification of position often only occurs during surgery, when it can be categorized as ‘intra-abdominal, intracanalicular, extracanilicular (suprapubic or infrapubic), or ectopic’ (Wein, 2007).
• There is also no single widely accepted theory on testicular descent and maldescent. Although new research is shedding light on the etiology of the disease, including maternal factors (Giordano et al., 2008), there have been no comprehensive evidence reviews to assess them.
• The effectiveness of early surgical repositioning of the testis to reduce the chances of infertility or subfertility remains controversial.
• Although there is growing evidence that early orchiopexy can reduce the risk of testicular neoplasia associated with cryptorchidism, the issue remains controversial as some of the literature reaches conflicting conclusions (Walsh, Dall'Era, Croughan, Carroll, & Turek, 2007; Wood & Elder, 2009).
• The effectiveness of various imaging modalities in localizing the testis is disputable. Some of the issues to be examined include lack of accuracy, high false negative rates, or in the case of magnetic resonance angiography (MRA), th

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

The AUA intends to use systematic reports developed by AHRQ on urologic topics such as cryptorchidism into evidence-based guidelines. The creation of an evidence report on this topic would allow the AUA to create a clinical practice guideline in a relatively short timeframe, as the data collection, extraction and analysis would have already have been completed in adherence with the highest standards of systematic review. With a staff of six full-time professionals as well as extensive consultant support, the AUA Guidelines Department is well positioned to develop high quality guidelines from evidence reviews in a timely, efficient, and effective manner. AUA guidelines are scientifically rigorous and evidence-based, and the organization has previously partnered with AHRQ in the development of an evidence report on the Management of Female Overactive Bladder (OAB). The AUA is currently developing the AHRQ report on OAB into a clinical practice guideline, and has established an efficient mechanism to do the same for any future AHRQ evidence reports on urologic topics. This mechanism will be further refined as the AUA develops a guideline on the Medical Management of Stones, another topic submitted by AUA and recently accepted by AHRQ.

The AUA Guidelines Department works closely with the AUA Foundation, dedicated to patient education and advocacy, to develop patient guides from its clinical practice guidelines. The development of a clinical practice guideline on cryptorchidism would thus enable the AUA to develop a patient guide on this condition as well. A strong focus on the importance of parental counseling and education would be an important component of such a product.

Describe the timeframe in which an answer to your question is needed.

AUA would hope to begin work on this guideline in late 2011 or early 2012, so it would be desirable to have the evidence report completed at this time.

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

• Cryptorchidism is strongly correlated with low birth weight which, as has long been established, is more prevalent in low income groups (Kramer, 1987), exposing them to higher risk of developing this condition.
• Cryptorchidism has been found to be more common among Asians, and delayed testicular descent has been correlated with ethnicity as well, being more common among Hispanics and Blacks (Berkowitz & Lapinski, 1996).

Nominator Information

Other Information About You: (optional)

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

The AUA intends to use systematic reports developed by AHRQ on urologic topics such as cryptorchidism into evidence-based guidelines. The creation of an evidence report on this topic would allow the AUA to create a clinical practice guideline in a relatively short timeframe, as the data collection, extraction and analysis would have already have been completed in adherence with the highest standards of systematic review. With a staff of six full-time professionals as well as extensive consultant support, the AUA Guidelines Department is well positioned to develop high quality guidelines from evidence reviews in a timely, efficient, and effective manner. AUA guidelines are scientifically rigorous and evidence-based, and the organization has previously partnered with AHRQ in the development of an evidence report on the Management of Female Overactive Bladder (OAB). The AUA is currently developing the AHRQ report on OAB into a clinical practice guideline, and has established an efficient mechanism to do the same for any future AHRQ evidence reports on urologic topics. This mechanism will be further refined as the AUA develops a guideline on the Medical Management of Stones, another topic submitted by AUA and recently accepted by AHRQ.

The AUA Guidelines Department works closely with the AUA Foundation, dedicated to patient education and advocacy, to develop patient guides from its clinical practice guidelines. The development of a clinical practice guideline on cryptorchidism would thus enable the AUA to develop a patient guide on this condition as well. A strong focus on the importance of parental counseling and education would be an important component of such a product.

Are you making a suggestion as an individual or on behalf of an organization?

Organization

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

Familiarity with AHRQ program in general.