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Timing for Surgery for Cryptorchidism: Is There a Consensus?
By: Nikhil V. Batra, MD; Romano T. DeMarco, MD; Christopher E. Bayne, MD | Posted on: 01 Oct 2022
The AUA guidelines on cryptorchidism recommend boys with an undescended testis which does not spontaneously descend by 6 months of age be referred to a specialist for surgery within the next year (see Figure).1 Other societal guidelines are similar or recommend surgery at even an earlier age. The term “timely orchidopexy” is commonly used to describe orchidopexy within the desired timeframe of 6 to 18 months of age. There is evidence orchidopexy timing trends have improved since publication of the first AUA cryptorchidism guidelines in 2014, yet a substantial proportion of children ages 1–5 years are still not undergoing timely orchidopexy.2 The purpose of this article is to briefly review the evidence for timely orchidopexy in the context of an ongoing global pandemic that may force clinicians to consider timing of referrals to a specialist or elective surgery.
Fertility
The temporal relationship between cryptorchidism and histological structural changes to the testes that impact fertility has been known and studied extensively for the better part of the last century. Early work by Hedinger in 1982 evaluated testicular biopsies from boys with undescended testes versus age-matched controls.3 He observed significant reductions in the number of germ cells per transverse tubular section (G/T ratio) and spermatogonia per transverse tubular section (S/T ratio) in boys in the second and third years of life compared to those in the first year of life.3 Since that time, an abundance of data support structural benefits to cryptorchid testes undergoing early orchidopexy, including a notable randomized trial in which Kollin et al reported improved volumetric and morphometric measurements in boys undergoing orchidopexy at 9 months compared to 3 years.4 Heterogeneity in study design has prevented robust systematic review.
Future fertility for boys born with unilateral cryptorchidism is thought to be generally excellent. Work by Lee and Coughlin in 2001 evaluated formerly cryptorchid boys versus normal controls in a prospective cohort study focused on paternity.5 No significant difference in paternity rates was observed between formerly unilateral cryptorchid men versus normal controls (93% vs 90%). Formerly bilateral cryptorchid men had significantly reduced rates of paternity at 67% despite prior surgical correction (p <0.001).5 Timing of surgery was not evaluated in their study. More contemporary data by Schneuer et al in 2018 support early repair based on paternity concerns.6 The authors prospectively followed a population-based cohort of boys born in Western Australia from 1977–1999 into adulthood. For every 6-month delay in orchidopexy after 18 months of age, the authors reported a 5% increased risk of need for future assisted reproductive therapy and 1% reduction in paternity.6
There is controversy whether current markers at the time of orchidopexy are prognostic for future fertility. Kraft et al found no significant association between total germ cell counts at the time of orchidopexy and hormone levels or semen analysis in adulthood in a cohort of formerly cryptorchid boys who underwent semen and hormone analyses at age 18 following prior surgical repair.7 These results may be most relevant in cases of unilateral cryptorchidism.
Malignancy
Data supporting early repair of cryptorchid testes to minimize the risk of malignancy are robust and widely accepted. Pettersson et al published a landmark study in 2007 reporting on the risk of carcinogenesis in nearly 17,000 patients undergoing orchidopexy between 1964 and 1999.8 The authors reported markedly reduced risk of carcinogenesis (2–6-fold reduction in relative risk) with surgical repair prior to puberty (defined as age 13 in their study), with a relative risk (RR) of malignancy of 2.23 in those undergoing orchidopexy prior to puberty versus a RR of 5.4 for those repaired after puberty.8 Large scale systematic review and meta-analysis by Cook et al9 and Banks et al10 have reiterated these findings. Cook et al reported a RR of 4.3 (95% CI 3.6–5.1) of malignancy in cryptorchid testes.9 Banks et al reported a RR of 3.1 (95% CI 1.6–5.8), 3.8 (95% CI 2.9–5.0), and 5.0 (95% CI 3.5–7.2) for boys undergoing orchidopexy in age groups 0–9 years, 10–14 years, and ≥15 years, respectively.10 The Schneuer et al prospective cohort of cryptorchid boys offered more concrete support for early surgical repair.6 Their group found a 6% increased risk for testicular cancer for every 6 months delay in orchidopexy after 18 months of age.
Conclusion
Strong data support early surgical repair of cryptorchidism. Timely orchidopexy seems to improve testicular volumetric and morphometric parameters, and delay in orchidopexy seems to have a defined impact on future fertility, though prognostic markers remain unclear. Puberty seems to have a strong impact on carcinogenesis of the cryptorchid testis, with children undergoing orchidopexy prior to puberty having 2–6-fold decreased risk of malignancy. Knowing these data, early in the pandemic it was our opinion that orchidopexy remained a time-sensitive procedure.
The AUA guidelines recommended children with an undescended testis be referred for surgical repair by 6 months of age and undergo surgical repair between 6–18 months. Most urologists are likely aware of these data, yet there have only been mild improvements in early orchidopexy rate since release of the guidelines; therefore, it seems likely community education on timing of referral is a critical step in improving timing of orchidopexy on a larger, population level.
- Kolon TF, Herndon CD, Baker LA, et al. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol. 2014;192(2):337-345.
- Holzman SA, Davis-Dao CA, Huen KH, et al. Timely orchiopexy by 18 months of age: are we meeting the standards defined by the 2014 AUA guidelines? J Pediatr Urol. 2022; https://doi.org/10.1016/j.jpurol.2022.07.008.
- Hedinger CE. Histopathology of undescended testes. Eur J Pediatr. 1982;139(4):266-271.
- Kollin C, Stukenborg JB, Nurmio M, et al. Boys with undescended testes: endocrine, volumetric and morphometric studies on testicular function before and after orchidopexy at nine months or three years of age. J Clin Endocrinol Metab. 2012;97(12):4588-4595.
- Lee PA, Coughlin MT: Fertility after bilateral cryptorchidism. Evaluation by paternity, hormone, and semen data. Horm Res. 2001;55(1):28-32.
- Schneuer FJ, Milne E, Jamieson SE, et al. Association between male genital anomalies and adult male reproductive disorders: a population-based data linkage study spanning more than 40 years. Lancet Child Adolesc Health. 2018;2(10):736-743.
- Kraft KH, Canning DA, Snyder HM 3rd, Kolon TF. Undescended testis histology correlation with adult hormone levels and semen analysis. J Urol. 2012;188(4 Suppl):1429-1435.
- Pettersson A, Richiardi L, Nordenskjold A, Kaijser M, Akre O. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med. 2007;356(18):1835-1841.
- Cook MB, Akre O, Forman D, Madigan MP, Richiardi L, McGlynn KA. A systematic review and meta-analysis of perinatal variables in relation to the risk of testicular cancer—experiences of the son. Int J Epidemiol. 2010;39(6):1605-1618.
- Banks K, Tuazon E, Berhane K, et al. Cryptorchidism and testicular germ cell tumors: comprehensive meta-analysis reveals that association between these conditions diminished over time and is modified by clinical characteristics. Front Endocrinol (Lausanne). 2013;3:182.
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