Outcomes and Evidence Based Medicine Systematic Reviews Management - PowerPoint PPT Presentation

Outcomes and Evidence Based Medicine Systematic Reviews Management of the Undescended Testicle Meghan A. Arnold, Karen Diefenbach, Robert Gates, Julia Shelton APSA Outcomes and Evidence Based Medicine Committee

Discl closures • We have no disclosures • There is some discussion of non-FDA approved therapies as some studies outside of the US have evaluated the use of LHRH analogs

Commonalities • UDT = failure of the testis to descend into a scrotal position • Extrascrotal (prescrotal, superficial inguinal pouch, external ring, canalicular, abdominal or ectopic) vs absent “vanishing” • Congenital vs acquired (ascending, entrapped, retractile, atrophic) • Orchidopexy = Orchiopexy https://uroweb.org/wp-content/uploads/EAU-Guidelines-Paediatric-Urology-2016-1.pdf

Questi tions s posed in t this s s systemati tic r review For children with undescended testicle 1. When is pre-operative imaging indicated and if so, which study is most appropriate? 2. What is the role of medical management in undescended testicle? 3. What is the appropriate timing of intervention and how is this affected by associated clinical factors? 4. What is the evidence supporting type of operative intervention? 5. What are the long term outcomes after orchiopexy? 5

Sea Search Resu esult lts • MeSH headings searched back to 2007: • Cryptorchid/cryptorchidism, undescended testicle/testis, orchidopexy/orchiopexy, intraabdominal testis, impalpable/nonpalpable testis, • Infant, child or adolescent • 417 articles total • All abstracts reviewed and categorized • Cross referenced between reviewers • Snowballing technique used to obtain additional papers • 388 chosen for full review • 180 included in the review

Question 1 For children with undescended testicle: When is pre-operative imaging indicated and if so, which study is most appropriate?

Sea Search Resu esult lts • 19 studies obtained from initial search • 5 added after further review • 7 suitable for inclusion – 3 prospective – 4 retrospective • Imaging modalities: MRI, CT and US

Consensus us S Statements • American Urological Association 2014 (http://www.auanet.org/guidelines/cryptorchidism-(published- 2014)) Providers should not perform ultrasound (US) or other imaging modalities in the evaluation of boys with cryptorchidism prior to referral, as these studies rarely assist in decision making • European Association of Urology 2016 (https://uroweb.org/wp-content/uploads/EAU-Guidelines- Paediatric-Urology-2016-1.pdf) Use of US, CT or MRI is limited and only recommended in specific and selected clinical scenarios

When i is pre-op oper erative e imagi ging g indicated ed? • Ultrasounds should not be obtained prior to being seen by surgeon (pediatric surgeon or pediatric urologist) Wayne et al. 2017 (Level II) and Kanaroglou et al. 2017 (Level II) - May not be necessary as >50% referrals were normal on exam by specialist (Wayne) - Children who had an US prior referral had an approximate 3 month delay in definitive surgical management (Kanaroglou) 10

When p pre-operativ ive im imaging is is in indic icated, , which study i is most appropri riate? • Cross-sectional imaging (CT/MRI) – no evidence that this is indicated for locating testes • May be helpful when evaluating for other anomalies associated with undescended testes

When p pre-operativ ive im imaging is is in indic icated, , which study i is most appropri riate? • Ultrasound may be helpful in select patients • Moriya et al. 2017 (Level III) • Berger et al. 2017 (Level II) • Abdulrahman et al. 2016 (Level III) • Vos et al. 2014 (Level II) • Adesanya et al. 2013 (Level II)

When p pre-operativ ive im imaging is is in indic icated, , which study i is most appropri riate? • Recommendations • Ultrasound may be helpful in select patients: • Patients with non-palpable testes (unilateral or bilateral) in which location may alter operative approach or avoid diagnostic laparoscopy (Abdulrahman, Vos, Adesanya) • Evaluation of volume of contralateral testis may predict viability or increase accuracy of approach (Moriya, Berger) (Level II-III evidence, Grade B recommendation)

Question 2 For children with undescended testicle: What is the role of medical management?

Sea Search Resu esult lts • 12 studies obtained from initial search • 1 added after further review • 7 suitable for inclusion • 4 prospective • 3 retrospective • Hormonal therapy investigated as • Medical therapy alone to induce descent • Adjuvant to surgery to improve fertility

Consensus us S Statements • American Urological Association 2014 (http://www.auanet.org/guidelines/cryptorchidism-(published-2014)) Providers should not use hormonal therapy to induce testicular descent as evidence shows low response rates and lack of evidence for long-term efficacy. • European Association of Urology 2016 (https://uroweb.org/wp-content/uploads/EAU-Guidelines-Paediatric- Urology-2016-1.pdf) Endocrine treatment to achieve testicular descent is not recommended. • Nordic consensus (Ritzen et al, 2007) Hormonal treatment following orchiopexy has been proposed to have beneficial effects on sperm count but these findings need confirmation by other groups before being incorporated into clinical practice. 16

What i is the role of medical management t in undescended d testicle? • Hormone therapy to induce descent of testes - Aycan et al. 2006 (Level II), Marchetti et al. 2012 (Level III), Pirgon et al. 2009 (Level III) - Variable results from >65% successful descent into scrotum (Aycan) to 25% (Marchetti) - May have side effects including increased left ventricular mass (Pirgon) 17

What i is the role of medical management t in undescended d testicle? • Hormone therapy as an adjuvant to surgery to improve fertility - Spinelli et al. 2014 (Level II) – GnRHa effect on TAIn - Thorup et al. 2012 (Level III) – endocrine and histopathology of testis in determining possible improvement of fertility after orchiopexy - Jallouli et al. 2009 (Level II) – GnRH effect on fertility index - Hadziselimovic 2008 (Level II) – LH-RH Analogue (GnRH) effect on sperm concentration after puberty 18

What i is the role of medical management t in undescended d testicle? • Hormone therapy as an adjuvant to surgery to improve fertility • Additional clinical information may be required: - Ultrasound of testes to determine volume and calculate TAIn - Endocrine evaluation (serum levels of LH, FSH, and inhibin B) - Histopathologic evaluation of testes (bilateral biopsy of testes) 19

What i is the role of medical management t in undescended d testicle? • Recommendations • Reserve consideration of hormonal therapy for select patients as it may improve fertility after orchiopexy (Level II evidence, Grade C recommendation)

Question 3 For children with undescended testicle: What is the appropriate timing of intervention and how is this affected by other clinical factors?

Consensus us S Statements – Timing o of f Orchi hiope pexy • American Urological Association 2014 (http://www.auanet.org/guidelines/cryptorchidism-(published- 2014)) <18 months • European Association of Urology 2016 (https://uroweb.org/wp-content/uploads/EAU-Guidelines- Paediatric-Urology-2016-1.pdf) Treatment should be completed by 12 months or 18 months at the latest • Nordic consensus (Ritzen et al, 2007) 6-12 months 22

Sea Search resu esult lts • 61 studies obtained from initial search • 22 added after further review • 16 suitable for inclusion • 6 prospective • 10 retrospective • Data on timing related to • Outcome • Testicular growth • Germ cell development • [Sperm count/extraction and testicular cancer discussed elsewhere] • Laterality • Associated gastroschisis/omphalocele • Concurrent inguinal hernia • No data on timing related to • Other comorbid conditions; associated torsion; palpable/non-palpable; symptoms; ascending/retractile 23

Timi ming o of Orchi hiope pexy – Testicular G r Growth • 4 papers representing 3 patient populations • Prospective RCT • Prospective case series • Retrospective • Kollin et al. 2006, 2007 • Kim et al. 2011 • Tseng et al. 2017 24

Timi ming o of Orchi hiope pexy – Testicular G r Growth • Kollin et al. 2006, 2007 • N = 155 boys with unilateral, UDT • Randomized at 6 months to surgery at 9 months or 3 years • Serial ultrasounds Testicular volume ratio (undescended/descended) 25

Timi ming o of Orchi hiope pexy – Testicular G r Growth • Kim et al. 2011 • N = 108 • Divided by age at orchiopexy • Group 1 = <2 years • Group 2 = ≥2 to <5 years • Group 3 = ≥5 years • Serial ultrasounds 26

Timi ming o of Orchi hiope pexy – Testicular G r Growth • Tseng et al. 2017 • N = 134 • Divided by age at orchiopexy • ≤ 1 year • >1 to ≤ 2 years • > 2 years • Serial ultrasounds 27

Timi ming o of Orchi hiope pexy – Testicular G r Growth • Recommendation • Orchiopexy should be performed between 9 months and 2 years of age to optimize testicular growth (Level II-III evidence, Grade B recommendation) 28