- Email: [email protected]
Factors associated with delay in undescended testis referral
Journal of Pediatric Urology (2019) 15, 380.e1e380.e6
Factors associated with delay in undescended testis referral a
Department of Urology, Oregon Health & Sciences University, Portland, OR, USA
b Department of Pediatric Urology, Doernbecher, Portland, OR, USA
* Corresponding author. Doernbecher Children’s Hospital, Department of Pediatric Urology, 700 S.W. Campus Drive, Portland, OR 97239, USA. Tel.: þ1 503 346 0640; fax: þ1 503 346 1501. [email protected] (C.A. Seideman) Keywords Undescended testis; Cryptorchidism; Timing; Delay in referral
Abbreviations UDT, Undescended testis; AUA, American Urological Association; EAU, European Association of Urology; MVA, Multivariate analysis; PCP, Primary care provider
D.D. Jiang a, A.M. Acevedo a, A. Bayne b, J.C. Austin b, C.A. Seideman b,* Summary Introduction Undescended testis (UDT) is one of the most common congenital disorders and is associated with infertility and testicular cancer. Multiple guidelines internationally have recommended orchiopexy by 18 months. Multiple large retrospective studies published in the last decade have found persistent delay in timing of orchiopexy.
Objective The aim of the study was to determine timing at which UDTs are referred at the tertiary pediatric hospital and assess factors that are associated with delay in UDT referral.
Study design Based on clinical observations and previous data, a series of clinical and socio-economic variables were constructed to design a prospective database. All patients who underwent orchiopexy for UDT from March 1, 2017, to August 31, 2018, were reviewed for demographic and clinical data. Referral appointments after 18 months were considered delayed. Factors associated with delay in UDT referral were analyzed using univariate and multivariate analysis with logistic regression.
Results Received 8 January 2019 Accepted 29 March 2019 Available online 4 April 2019
of them had delay in referral. On univariate analysis, normal birth testicular examination, diagnosis of ‘retractile testicle,’ long gap without seeing pediatrician, diagnosis by a new physician, and primary language non-English were associated with delayed UDT referral. On multivariate analysis, delayed referral was associated with normal testicular examination at birth, history of ‘retractile testis,’ diagnosis not by the regular primary care provider, and other health or social issues that may have led to delay.
One hundred seventy-eight patients underwent orchiopexy for UDT. The median age was 44 months, and 64%
Discussion This is the first prospective study analyzing timing of referral for boys with cryptorchidism. It was found that timing of treatment of UDT with orchiopexy has not improved over the last decade. Major causes in delay in referral may be due to poor of education of families and lack of routine testicular examinations by referring providers. Secondary ascent may account a significant number of delayed orchiopexy cases.
Conclusion Most patients at Doernbecher had delayed referral of cryptorchidism. Factors associated with delay were determined. To improve treatment of cryptorchidism, quality-based interventions and the importance of education and routine testicular examinations need to be focused on.
Figure https://doi.org/10.1016/j.jpurol.2019.03.029 1477-5131/ª 2019 Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company.
Factors associated with delay in undescended testis referral
Introduction Cryptorchidism is one of the most common congenital disorders in males. It has been reported that 1.0e4.6% of fullterm infants have undescended testis (UDT) [1]. The incidence is even higher in premature and low birth weight infants with reports up to 45% [1,2]. Although UDT after birth can undergo spontaneous descent within the first few months of life, this event is uncommon and rare beyond 6 months of age [3]. Furthermore, evidence exists to support that the testis can undergo secondary ascent after being down in the scrotum [4]. Cryptorchidism has been found to be a risk factor for testicular cancer with increased risk if treated after puberty [5,6]. It has also been associated with compromised fertility [7]. In 1996, American Academy of Pediatrics guidelines formally recommended surgical repair by the age of one for boys with UDT [8]. More recently, American Urologic Association and European Association of Urology/European Society for Paediatric Urology have released consensus guideline statements recommending treatment of orchiopexy by 18 months at the latest [9,10]. A recent large population-based cohort study concluded that for every 6-month delay in orchiopexy, there is a 6% increase in risk of testicular cancer, a 5% increase in risk of future use of assisted reproductive technologies, and 1% reduction in paternity [11]. Despite clear consensus guideline statements, multiple large retrospective studies in the United States, as well as globally, have found persistent delay in the timing of orchiopexy, with less than half of the patients receiving orchiopexy in a timely manner [12e20]. Factors associated with delay in orchiopexy vary between studies. It is hypothesized in many of these studies that lack of education or full examinations by the referral provider contribute to the either referral or diagnostic delay [13e18]. An additional hypothesis is that the rate of secondary testicular ascent is much higher than traditionally estimated; reported rates of orchiopexy due to secondary ascent vary greatly from 2% to 73% [4]. The timing at which UDTs are referred at the tertiary pediatric hospital was determined. Furthermore, the aim was to define which social, clinical, and demographic factors are associated with delayed referral. It was hypothesized that a significant portion of patients with cryptorchidism seen at the institution are older than 18 months and that inadequate genital examinations by primary care providers (PCPs) may be contributing to the delay.
Materials and methods Based on clinical observations and previous data, a series of clinical and socio-economic variables were constructed to design a prospective database (Supplemental Data). After obtaining institutional review board approval (IRB 000169916), these elements were prospectively collected during clinic visits on all boys with UDT on examination at Doernbecher Children’s Hospital (Portland, OR). The data were collected from the referral packet, chart review; if those were not available, parents’ recall was used. All
380.e2 patients who underwent orchiopexy for UDT from March 1, 2017, to August 31, 2018, were reviewed for demographic and clinical data. Referral appointments after 18 months of age were considered delayed. Factors associated with delay in UDT referral were explored using univariable analysis (body mass index [BMI], birth testicular examination, examination documented in subsequent visits, parents’ recall of examination, told it come down later, diagnosis of retractile testis, any issues causing delay, long gap without seeing pediatrician, circumcision at birth, person who discovered the issue, primary language at home, distance to facility, insurance, and unilateral or bilateral). Those factors significant on univariate analysis were then used in the multivariable analysis model with logistic regression. All statistical analyses were performed using Stata/MP version 14.1.
Results During the 18-month study period, 178 patients underwent routine orchiopexy for UDT. The median age of referral visit was 44 months (interquartile range [IQR], 11e91); of those, 114 (64%) patients were seen after 18 months of age (Fig. 1). The majority of patients had an abnormal testicular examination at birth (61%). Apart from birth examination, genital examinations were documented in 89% of patients, and almost all parents (93%) recall genital examinations at the PCP office (Table 1). A third (35%) of the patients were told it would come down later, and 22% were previously diagnosed as ‘retractile testicle.’ Only 7% of patients had a long gap without seeing a pediatrician (>1.5 years). Approximately two-thirds of the patients (62%) were diagnosed by their regular PCP, 38% of the patients were diagnosed by a new PCP, a specialty provider, the emergency department, the parent, or the patient himself. Fifteen percent of the patients have a family history of undescended testis. It was also noted that 28% had bilateral UDT and 45% had a patent processus vaginalis with UDT on at least one side. On univariate analysis (Table 2), normal birth testicular examination (P < 0.001), diagnosis of retractile testicle (P < 0.001), long gap without seeing a pediatrician (P Z 0.004), discovery not by the regular PCP (P < 0.001), and primary language not English at home (P Z 0.011) were associated with delay in UDT referral. Of those patients who were found to have other potential health or social issues that may have contributed to delay, 83% were seen for referral after 18 months, which was also statistically significant (P Z 0.001). On multivariate analysis (MVA) (Table 3), after controlling for significant variables from the univariate analysis, delayed UDT referral was associated with normal birth examination (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.3e2.7; P < 0.001), diagnosis of ‘retractile testis’ (OR, 3.2; 95% CI, 1.4e7.2; P Z 0.004), health or social issues that may have led to delay (OR, 3.6; 95% CI, 1.2e11.0; P Z 0.024), and discovery by someone who is not the patient’s regular PCP (OR, 4.3; 95% CI, 1.4e13.2; P Z 0.010). Primary language non-English was not significant on multivariable analysis, P Z 0.268.
380.e3
D.D. Jiang et al.
Fig. 1 Histogram representing age at referral. The red line demarcates the 18-month mark. All patients later than this line represent delayed referral, which represents 64% of the total patients. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
Discussion There have been many national retrospective studies evaluating the timing of orchiopexy [12,13,15,16,18,20]. This study is the first prospective analysis of children with
Table 1
Baseline characteristics of patients (n Z 178).
Baseline characteristics (n Z 178) Age in months (median, IQR) Age at referral visit>18 mo BMI (median, IQR) Abnormal examination at birth Examination documented in subsequent wellchild visit Parents remember genital examinations at the pediatrician They were told it would come down later Diagnosed as retractile testicle Any issue causing delay Long gap without seeing a pediatrician Circumcised at birth Regular PCP discovered it Family history of UDT Primary language not English Distance Local Regional Beyond Private insurance Bilateral UDT
44 (11e91) 114 (64%) 17 (16e19) 88 (61%) 133 (89%) 140 (93%) 56 (35%) 36 (22%) 52 (29%) 12 (7%) 85 (49%) 111 (62%) 26 (15%) 24 (13%) 52 72 54 75 50
(29%) (40%) (30%) (42%) (28%)
BMI, body mass index; IQR, interquartile range; PCP, primary care provider; UDT, undescended testis.
cryptorchidism. The largest retrospective study was by McCabe and Kenny [20] from the United Kingdom (UK). Between 1997 and 2005, approximately 35 thousand orchiopexies were performed in the UK, and 76% of them were performed after the age of two years; they found that the type of surgeon (urologist vs. pediatric surgeon vs. general surgeon) was associated with delay of orchiopexy [20]. The largest study in the United States identified 28,000 children from the Pediatric Health Information System who underwent orchiopexy between 1999 and 2008; 57% had orchiopexy after age of two years [12]. This study found that race, insurance status, and treating hospital were significantly associated with timing of orchiopexy [12]. A study in the USA in patients with private insurance (UnitedHealthcare) between 2002 and 2007 found that 87% of children had a timely orchiopexy before 18 months of age; they found that the number of well-care visits and examination by pediatricians rather than family medicine providers were more likely to refer in a timely manner [13]. However, this study excluded patients aged more than five years, those with low birth weight and prematurity, and those with complex genital conditions. Interestingly, this study did not demonstrate insurance status or number of well-child visits to be associated with delay in care. The institution was part of a multicenter study in 1995 reviewing the timing of orchiopexy. In that study, the mean age at surgery was 4.2 years [21]. Despite the number of studies on this subject and highlighting the importance of early intervention, the referral age of boys with cryptorchidism was not improved over the past two decades. It was found that most patients at Doernbecher who received treatment for UDT had a delayed referral, with 64% of patients seen after 18 months of age. Referrals at the institution were processed in a timely manner, with most patients being seen within 2 months of referral. The
Factors associated with delay in undescended testis referral Table 2
380.e4
Univariate analysis of variables with regard to delayed referral (>18 months).
Univariate analysis Clinical variables BMI Birth testicular examination Examination documented in subsequent visits Parents remember GU examinations at the PCP Told it would come down later Diagnosed as retractile testicle Any issues causing delay Long gap without seeing a pediatrician Circumcised at birth Who discovered it Family History of UDT Primary language Distance
Insurance Unilateral or bilateral
Not normal Normal Not documented Documented No Yes No Yes, wait No Yes No Yes No Yes No Yes PCP Other provider No Yes English Not English Local Regional Beyond Private Medicaid Unilateral Bilateral
18 mo
Delayed >18 mo
P-value
17.5 (2.7) 53 (60%) 7 (13%) 4 (25%) 60 (45%) 1 (9%) 63 (45%) 40 (38%) 22 (39%) 62 (49%) 2 (6%) 55 (44%) 9 (17%) 64 (40%) 0 (0%) 29 (33%) 34 (40%) 57 (51%) 7 (10%) 57 (40%) 6 (23%) 61 (40%) 3 (13%) 23 (44%) 25 (35%) 16 (30%) 29 (39%) 35 (34%) 48 (38%) 16 (32%)
18.3 (3.7) 35 (40%) 49 (88%) 12 (75%) 73 (55%) 10 (91%) 77 (55%) 66 (62%) 34 (61%) 64 (51%) 34 (94%) 71 (56%) 43 (83%) 98 (60%) 12 (100%) 58 (67%) 51 (60%) 54 (49%) 60 (90%) 86 (60%) 20 (77%) 93 (60%) 21 (88%) 29 (56%) 47 (65%) 38 (70%) 46 (61%) 68 (66%) 80 (63%) 34 (68%)
0.175 <0.001 0.125 0.025 0.847 <0.001 0.001 0.004 0.364 <0.001 0.104 0.011 0.282
0.520 0.492
Significant P-values are highlighted in bold. Chi-squared analysis was used for all except for long gap without seeing a pediatrician (Fisher’s exact test), retractile testis diagnosis (Fisher’s exact test), primary language at home (Fisher’s exact test), and BMI (t-test). BMI, body mass index; PCP, primary care provider; GU, genitourinary; UDT, undescended testis.
majority of patients (61%) had an abnormal testicular examination at birth. Interestingly, 15% of the patients in the cohort had a family history of UDT, yet 77% of patients with a family history had a delay in UDT referral. Primary language non-English at home was associated with 88% rate of referral delay compared with 60% for those who speak English primarily; this was statistically significant on Chisquared analysis (P Z 0.011), but it was not significant on multivariable analysis. This may suggest a deficiency in the education of the family regarding the diagnosis of cryptorchidism or improper counseling. An area of future improvement is targeting education of the family to ensure full comprehension, especially for those who do not speak English as a primary language at home. It was found that the patient, his family, or another provider who was not their regular PCP was more likely to discover the UDT. This scenario is encountered when a toddler transfers care; the new pediatrician does a complete history and physical examination and discovers the UDT that had remained undiagnosed. Another scenario is when an infant is found to have an undescended testicle on examination but is told to wait by the PCP for more than
one year. These findings indicate a lack of education or failure of complete physical examination by the regular PCP, which is an area of improvement. Targeted intervention toward PCPs has previously been performed with success [22]. A hospital in the UK was able to reduce the median age to surgery for cryptorchidism by 2.5 years with a multimodal quality improvement project [22]. The initial hospital audit between 1992 and 1994 revealed a median age of orchiopexy of 4 years; they identified delayed referral as the major culprit, with 45% of patients who were self-referred after parents noticed the issue. They initiated a mandatory 8-month check by general practitioners (GPs). They disseminated the information to GPs in writing as well as in education events for primary care and hospital staff in 1997. They also made information leaflets for parents and management guidelines for junior pediatric staff. For patients who had UDT at birth, a special written reminder slip was added to the personal child health record at the 8-month tab to prompt the GP to place the referral. With these changes, they were able to reduce their median age of orchiopexy from 4.5 in 1996 to 2.0 in 2001 [22].
380.e5 Table 3
D.D. Jiang et al. Multivariate analysis of variables.
Factors associated with delayed UDT >18 mo (MVA logistic regression results) Clinical variables
Odds ratio
95% CI
P value
Normal birth examination Retractile testicle diagnosis Primary language not English Any potential issues leading to delay Not discovered by the regular PCP
1.9 3.2 2.4 3.6 4.3
1.3e2.7 1.3e7.2 0.5e11.1 1.2e11.0 1.4e13.3
<0.001 0.004 0.268 0.024 0.010
Associated diagnosis of retractile testicle, primary language at home not English, discovery by a new PCP, discovery by someone other than PCP. Statistically significant factors are highlighted in bold. CI, confidence interval; MVA, multivariate analysis; PCP, primary care provider; UDT, undescended testis.
Another important aspect of delay in referral is the possibility of secondary ascent or acquired UDT. Traditionally, this was believed to be a rare occurrence [23]; however, in a large UK prospective study, the incidence of congenital cryptorchidism was 1.6% at 3 months, but the cumulative orchiopexy rate in the country was 3% [24]. Other single-institutional studies also support a significant rate of ascending testes as the explanation for the delay in treatment [25,26]. In a larger retrospective study, the rate of ascended testis was found to be 44% and associated with a history of being retractile [25]. With regard to the study, 39% of the patients had a normal testicular examination at birth. Furthermore, MVA demonstrated that ‘retractile testis’ diagnosis increased the risk of referral delay by approximately 3-fold. These findings are also consistent with a recent review analysis on cryptorchidism [27]. Although strict-protocolled temporal testicular examinations that may provide insight into the true rate of secondary assent were lacking, these findings suggest a significant number of patients can have secondary ascent. Furthermore, it highlights the importance of thorough annual testicular examinations even in patients with previously normal findings. For an ad hoc subanalysis, patients who had a normal testicular examination at birth (n Z 56) were excluded: the median age at the referral visit was 24 months (IQR, 8e72), and 65 patients (53%) were seen after the age of 18 months. For these patients compared with allcomers, the median age at the referral visit decreased by almost half, but more than half the patients still had a delay in referral. These findings highlight that secondary ascent may account for a significant number of delayed orchiopexies, but there are still areas of improvement even when these are excluded from analyses. Twenty-nine percent of patients were identified with either health or social complications that may have led to delay in care. For example, many health concerns affecting the child such as serious cardiopulmonary defects, serious congenital pathologies, and psychiatric problems were identified. Other non-clinically related concerns such as adoption, foster home, lack of insurance, and refugee status contributed to some of the patient delay. These possible reasons of delays were not homogenous. Care for pediatric patients can be challenging; clinicians need to address not only the needs of the patient but also the family’s. There are limitations to this study. The cohort of patients is small, with only 178 patients; it may not be powered to detect subtle differences in factors such as BMI or insurance
that may contribute to delay. In addition, there are other potential factors that may contribute to delay in referral that are not captured including palpable or non-palpable testis, other concurrent genitourinary abnormalities, income, race, and so on. Race was not included in this study because of the lack of diversity in the region, thus making it difficult to be powered appropriately. Another potential source of bias was parents’ recall when documentation of the newborn and subsequent genital examinations was not available. Additionally, a control cohort, such as retractile testicles, was not included to use a comparison. Although this study is limited to just over one year, the reported rates of delayed referral are similar to previously reported rates.
Conclusion Within the tertiary pediatric hospital, 64% of patients who underwent orchiopexy had a delay for the referral visit at age greater than 18 months. This was associated with the diagnosis of ‘retractile testis,’ non-English primary language, and discovery by someone who is not the routine PCP. Secondary ascent may play a significant role, representing up to 39% of cryptorchidism. Future efforts to improve timing of referral are underway.
Author statements Ethical approval The study was approved by the IRB (IRB 000169916).
Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-forprofit sectors.
Competing interests None declared.
Disclaimer The opinions expressed in this article are the authors’ own and do not reflect those of the Doernbecher Children’s Hospital.
Factors associated with delay in undescended testis referral
References [1] Sijstermans K, Hack WW, Meijer RW, et al. The frequency of undescended testis from birth to adulthood: a review. Int J Androl 2008;31:1e11. [2] Buemann B, Henriksen H, Villumsen AL, et al. Incidence of undescended testis in the newborn. Acta Chir Scand Suppl 1961;(Suppl. 283):289e93. [3] Wenzler DL, Bloom DA, Park JM. What is the rate of spontaneous testicular descent in infants with cryptorchidism? J Urol 2004;171:849e51. [4] Taghizadeh AK, Thomas DF. Ascent of the testis revisited: fact not fiction. BJU Int 2008;102:676e8. [5] Pettersson A, Richiardi L, Nordenskjold A, et al. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med 2007;356:1835e41. [6] Walsh TJ, Dall’Era MA, Croughan MS, et al. Prepubertal orchiopexy for cryptorchidism may be associated with lower risk of testicular cancer. J Urol 2007;178:1440e6. discussion 1446. [7] Lee PA. Fertility after cryptorchidism: epidemiology and other outcome studies. Urology 2005;66:427e31. [8] Timing of elective surgery on the genitalia of male children with particular reference to the risks, benefits, and psychological effects of surgery and anesthesia. American Academy of Pediatrics. Pediatrics 1996;97:590e4. [9] Kolon TF, Herndon CD, Baker LA, et al. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol 2014;192: 337e45. [10] Radmayr C, Dogan HS, Hoebeke P, et al. Management of undescended testes: European association of Urology/European Society for Paediatric Urology guidelines. J Pediatr Urol 2016; 12:335e43. [11] 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 2018:736e43. [12] Kokorowski PJ, Routh JC, Graham DA, et al. Variations in timing of surgery among boys who underwent orchidopexy for cryptorchidism. Pediatrics 2010;126:e576e82. [13] Yiee JH, Saigal CS, Lai J, et al. Timing of orchiopexy in the United States: a quality-of-care indicator. Urology 2012;80:1121e6. [14] Bradshaw CJ, Corbet-Burcher G, Hitchcock R. Age at orchidopexy in the UK: has new evidence changed practice? J Pediatr Urol 2014;10:758e62.
380.e6 [15] Bruijnen CJ, Vogels HD, Beasley SW. Age at orchidopexy as an indicator of the quality of regional child health services. J Paediatr Child Health 2012;48:556e9. [16] Hidas G, Ben Chaim J, Udassin R, et al. Timing of orchidopexy for undescended testis in Israel: a quality of care study. Isr Med Assoc J 2016;18:697e700. [17] Wei Y, Wu SD, Wang YC, et al. A 22-year retrospective study: educational update and new referral pattern of age at orchidopexy. BJU Int 2016;118:987e93. [18] Hrivatakis G, Astfalk W, Schmidt A, et al. The timing of surgery for undescended testis e a retrospective multicenter analysis. Dtsch Arztebl Int 2014;111:649e57. [19] Bayne AP, Alonzo DG, Hsieh MH, et al. Impact of anatomical and socioeconomic factors on timing of urological consultation for boys with cryptorchidism. J Urol 2011;186:1601e5. [20] McCabe JE, Kenny SE. Orchidopexy for undescended testis in England: is it evidence based? J Pediatr Surg 2008;43:353e7. [21] Steckler RE, Zaontz MR, Skoog SJ, et al. Cryptorchidism, pediatricians, and family practitioners: patterns of practice and referral. J Pediatr 1995;127:948e51. [22] Brown JJ, Wacogne I, Fleckney S, et al. Achieving early surgery for undescended testes: quality improvement through a multifaceted approach to guideline implementation. Child Care Health Dev 2004;30:97e102. [23] Stec AA, Thomas JC, DeMarco RT, et al. Incidence of testicular ascent in boys with retractile testes. J Urol 2007;178:1722e4. discussion 1724-5. [24] Cryptorchidism: a prospective study of 7500 consecutive male births, 1984-8. John Radcliffe hospital cryptorchidism study Group. Arch Dis Child 1992;67:892e9. [25] Guven A, Kogan BA. Undescended testis in older boys: further evidence that ascending testes are common. J Pediatr Surg 2008;43:1700e4. [26] Gracia J, Navarro E, Guirado F, et al. Spontaneous ascent of the testis. Br J Urol 1997;79:113e5. [27] Thorup J, Cortes D. Surgical management of undescended testis - Timetable and outcome: a debate. Sex Dev 2019.
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jpurol.2019.03.029.
Factors associated with delay in undescended testis referral a
Department of Urology, Oregon Health & Sciences University, Portland, OR, USA
b Department of Pediatric Urology, Doernbecher, Portland, OR, USA
* Corresponding author. Doernbecher Children’s Hospital, Department of Pediatric Urology, 700 S.W. Campus Drive, Portland, OR 97239, USA. Tel.: þ1 503 346 0640; fax: þ1 503 346 1501. [email protected] (C.A. Seideman) Keywords Undescended testis; Cryptorchidism; Timing; Delay in referral
Abbreviations UDT, Undescended testis; AUA, American Urological Association; EAU, European Association of Urology; MVA, Multivariate analysis; PCP, Primary care provider
D.D. Jiang a, A.M. Acevedo a, A. Bayne b, J.C. Austin b, C.A. Seideman b,* Summary Introduction Undescended testis (UDT) is one of the most common congenital disorders and is associated with infertility and testicular cancer. Multiple guidelines internationally have recommended orchiopexy by 18 months. Multiple large retrospective studies published in the last decade have found persistent delay in timing of orchiopexy.
Objective The aim of the study was to determine timing at which UDTs are referred at the tertiary pediatric hospital and assess factors that are associated with delay in UDT referral.
Study design Based on clinical observations and previous data, a series of clinical and socio-economic variables were constructed to design a prospective database. All patients who underwent orchiopexy for UDT from March 1, 2017, to August 31, 2018, were reviewed for demographic and clinical data. Referral appointments after 18 months were considered delayed. Factors associated with delay in UDT referral were analyzed using univariate and multivariate analysis with logistic regression.
Results Received 8 January 2019 Accepted 29 March 2019 Available online 4 April 2019
of them had delay in referral. On univariate analysis, normal birth testicular examination, diagnosis of ‘retractile testicle,’ long gap without seeing pediatrician, diagnosis by a new physician, and primary language non-English were associated with delayed UDT referral. On multivariate analysis, delayed referral was associated with normal testicular examination at birth, history of ‘retractile testis,’ diagnosis not by the regular primary care provider, and other health or social issues that may have led to delay.
One hundred seventy-eight patients underwent orchiopexy for UDT. The median age was 44 months, and 64%
Discussion This is the first prospective study analyzing timing of referral for boys with cryptorchidism. It was found that timing of treatment of UDT with orchiopexy has not improved over the last decade. Major causes in delay in referral may be due to poor of education of families and lack of routine testicular examinations by referring providers. Secondary ascent may account a significant number of delayed orchiopexy cases.
Conclusion Most patients at Doernbecher had delayed referral of cryptorchidism. Factors associated with delay were determined. To improve treatment of cryptorchidism, quality-based interventions and the importance of education and routine testicular examinations need to be focused on.
Figure https://doi.org/10.1016/j.jpurol.2019.03.029 1477-5131/ª 2019 Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company.
Factors associated with delay in undescended testis referral
Introduction Cryptorchidism is one of the most common congenital disorders in males. It has been reported that 1.0e4.6% of fullterm infants have undescended testis (UDT) [1]. The incidence is even higher in premature and low birth weight infants with reports up to 45% [1,2]. Although UDT after birth can undergo spontaneous descent within the first few months of life, this event is uncommon and rare beyond 6 months of age [3]. Furthermore, evidence exists to support that the testis can undergo secondary ascent after being down in the scrotum [4]. Cryptorchidism has been found to be a risk factor for testicular cancer with increased risk if treated after puberty [5,6]. It has also been associated with compromised fertility [7]. In 1996, American Academy of Pediatrics guidelines formally recommended surgical repair by the age of one for boys with UDT [8]. More recently, American Urologic Association and European Association of Urology/European Society for Paediatric Urology have released consensus guideline statements recommending treatment of orchiopexy by 18 months at the latest [9,10]. A recent large population-based cohort study concluded that for every 6-month delay in orchiopexy, there is a 6% increase in risk of testicular cancer, a 5% increase in risk of future use of assisted reproductive technologies, and 1% reduction in paternity [11]. Despite clear consensus guideline statements, multiple large retrospective studies in the United States, as well as globally, have found persistent delay in the timing of orchiopexy, with less than half of the patients receiving orchiopexy in a timely manner [12e20]. Factors associated with delay in orchiopexy vary between studies. It is hypothesized in many of these studies that lack of education or full examinations by the referral provider contribute to the either referral or diagnostic delay [13e18]. An additional hypothesis is that the rate of secondary testicular ascent is much higher than traditionally estimated; reported rates of orchiopexy due to secondary ascent vary greatly from 2% to 73% [4]. The timing at which UDTs are referred at the tertiary pediatric hospital was determined. Furthermore, the aim was to define which social, clinical, and demographic factors are associated with delayed referral. It was hypothesized that a significant portion of patients with cryptorchidism seen at the institution are older than 18 months and that inadequate genital examinations by primary care providers (PCPs) may be contributing to the delay.
Materials and methods Based on clinical observations and previous data, a series of clinical and socio-economic variables were constructed to design a prospective database (Supplemental Data). After obtaining institutional review board approval (IRB 000169916), these elements were prospectively collected during clinic visits on all boys with UDT on examination at Doernbecher Children’s Hospital (Portland, OR). The data were collected from the referral packet, chart review; if those were not available, parents’ recall was used. All
380.e2 patients who underwent orchiopexy for UDT from March 1, 2017, to August 31, 2018, were reviewed for demographic and clinical data. Referral appointments after 18 months of age were considered delayed. Factors associated with delay in UDT referral were explored using univariable analysis (body mass index [BMI], birth testicular examination, examination documented in subsequent visits, parents’ recall of examination, told it come down later, diagnosis of retractile testis, any issues causing delay, long gap without seeing pediatrician, circumcision at birth, person who discovered the issue, primary language at home, distance to facility, insurance, and unilateral or bilateral). Those factors significant on univariate analysis were then used in the multivariable analysis model with logistic regression. All statistical analyses were performed using Stata/MP version 14.1.
Results During the 18-month study period, 178 patients underwent routine orchiopexy for UDT. The median age of referral visit was 44 months (interquartile range [IQR], 11e91); of those, 114 (64%) patients were seen after 18 months of age (Fig. 1). The majority of patients had an abnormal testicular examination at birth (61%). Apart from birth examination, genital examinations were documented in 89% of patients, and almost all parents (93%) recall genital examinations at the PCP office (Table 1). A third (35%) of the patients were told it would come down later, and 22% were previously diagnosed as ‘retractile testicle.’ Only 7% of patients had a long gap without seeing a pediatrician (>1.5 years). Approximately two-thirds of the patients (62%) were diagnosed by their regular PCP, 38% of the patients were diagnosed by a new PCP, a specialty provider, the emergency department, the parent, or the patient himself. Fifteen percent of the patients have a family history of undescended testis. It was also noted that 28% had bilateral UDT and 45% had a patent processus vaginalis with UDT on at least one side. On univariate analysis (Table 2), normal birth testicular examination (P < 0.001), diagnosis of retractile testicle (P < 0.001), long gap without seeing a pediatrician (P Z 0.004), discovery not by the regular PCP (P < 0.001), and primary language not English at home (P Z 0.011) were associated with delay in UDT referral. Of those patients who were found to have other potential health or social issues that may have contributed to delay, 83% were seen for referral after 18 months, which was also statistically significant (P Z 0.001). On multivariate analysis (MVA) (Table 3), after controlling for significant variables from the univariate analysis, delayed UDT referral was associated with normal birth examination (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.3e2.7; P < 0.001), diagnosis of ‘retractile testis’ (OR, 3.2; 95% CI, 1.4e7.2; P Z 0.004), health or social issues that may have led to delay (OR, 3.6; 95% CI, 1.2e11.0; P Z 0.024), and discovery by someone who is not the patient’s regular PCP (OR, 4.3; 95% CI, 1.4e13.2; P Z 0.010). Primary language non-English was not significant on multivariable analysis, P Z 0.268.
380.e3
D.D. Jiang et al.
Fig. 1 Histogram representing age at referral. The red line demarcates the 18-month mark. All patients later than this line represent delayed referral, which represents 64% of the total patients. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
Discussion There have been many national retrospective studies evaluating the timing of orchiopexy [12,13,15,16,18,20]. This study is the first prospective analysis of children with
Table 1
Baseline characteristics of patients (n Z 178).
Baseline characteristics (n Z 178) Age in months (median, IQR) Age at referral visit>18 mo BMI (median, IQR) Abnormal examination at birth Examination documented in subsequent wellchild visit Parents remember genital examinations at the pediatrician They were told it would come down later Diagnosed as retractile testicle Any issue causing delay Long gap without seeing a pediatrician Circumcised at birth Regular PCP discovered it Family history of UDT Primary language not English Distance Local Regional Beyond Private insurance Bilateral UDT
44 (11e91) 114 (64%) 17 (16e19) 88 (61%) 133 (89%) 140 (93%) 56 (35%) 36 (22%) 52 (29%) 12 (7%) 85 (49%) 111 (62%) 26 (15%) 24 (13%) 52 72 54 75 50
(29%) (40%) (30%) (42%) (28%)
BMI, body mass index; IQR, interquartile range; PCP, primary care provider; UDT, undescended testis.
cryptorchidism. The largest retrospective study was by McCabe and Kenny [20] from the United Kingdom (UK). Between 1997 and 2005, approximately 35 thousand orchiopexies were performed in the UK, and 76% of them were performed after the age of two years; they found that the type of surgeon (urologist vs. pediatric surgeon vs. general surgeon) was associated with delay of orchiopexy [20]. The largest study in the United States identified 28,000 children from the Pediatric Health Information System who underwent orchiopexy between 1999 and 2008; 57% had orchiopexy after age of two years [12]. This study found that race, insurance status, and treating hospital were significantly associated with timing of orchiopexy [12]. A study in the USA in patients with private insurance (UnitedHealthcare) between 2002 and 2007 found that 87% of children had a timely orchiopexy before 18 months of age; they found that the number of well-care visits and examination by pediatricians rather than family medicine providers were more likely to refer in a timely manner [13]. However, this study excluded patients aged more than five years, those with low birth weight and prematurity, and those with complex genital conditions. Interestingly, this study did not demonstrate insurance status or number of well-child visits to be associated with delay in care. The institution was part of a multicenter study in 1995 reviewing the timing of orchiopexy. In that study, the mean age at surgery was 4.2 years [21]. Despite the number of studies on this subject and highlighting the importance of early intervention, the referral age of boys with cryptorchidism was not improved over the past two decades. It was found that most patients at Doernbecher who received treatment for UDT had a delayed referral, with 64% of patients seen after 18 months of age. Referrals at the institution were processed in a timely manner, with most patients being seen within 2 months of referral. The
Factors associated with delay in undescended testis referral Table 2
380.e4
Univariate analysis of variables with regard to delayed referral (>18 months).
Univariate analysis Clinical variables BMI Birth testicular examination Examination documented in subsequent visits Parents remember GU examinations at the PCP Told it would come down later Diagnosed as retractile testicle Any issues causing delay Long gap without seeing a pediatrician Circumcised at birth Who discovered it Family History of UDT Primary language Distance
Insurance Unilateral or bilateral
Not normal Normal Not documented Documented No Yes No Yes, wait No Yes No Yes No Yes No Yes PCP Other provider No Yes English Not English Local Regional Beyond Private Medicaid Unilateral Bilateral
18 mo
Delayed >18 mo
P-value
17.5 (2.7) 53 (60%) 7 (13%) 4 (25%) 60 (45%) 1 (9%) 63 (45%) 40 (38%) 22 (39%) 62 (49%) 2 (6%) 55 (44%) 9 (17%) 64 (40%) 0 (0%) 29 (33%) 34 (40%) 57 (51%) 7 (10%) 57 (40%) 6 (23%) 61 (40%) 3 (13%) 23 (44%) 25 (35%) 16 (30%) 29 (39%) 35 (34%) 48 (38%) 16 (32%)
18.3 (3.7) 35 (40%) 49 (88%) 12 (75%) 73 (55%) 10 (91%) 77 (55%) 66 (62%) 34 (61%) 64 (51%) 34 (94%) 71 (56%) 43 (83%) 98 (60%) 12 (100%) 58 (67%) 51 (60%) 54 (49%) 60 (90%) 86 (60%) 20 (77%) 93 (60%) 21 (88%) 29 (56%) 47 (65%) 38 (70%) 46 (61%) 68 (66%) 80 (63%) 34 (68%)
0.175 <0.001 0.125 0.025 0.847 <0.001 0.001 0.004 0.364 <0.001 0.104 0.011 0.282
0.520 0.492
Significant P-values are highlighted in bold. Chi-squared analysis was used for all except for long gap without seeing a pediatrician (Fisher’s exact test), retractile testis diagnosis (Fisher’s exact test), primary language at home (Fisher’s exact test), and BMI (t-test). BMI, body mass index; PCP, primary care provider; GU, genitourinary; UDT, undescended testis.
majority of patients (61%) had an abnormal testicular examination at birth. Interestingly, 15% of the patients in the cohort had a family history of UDT, yet 77% of patients with a family history had a delay in UDT referral. Primary language non-English at home was associated with 88% rate of referral delay compared with 60% for those who speak English primarily; this was statistically significant on Chisquared analysis (P Z 0.011), but it was not significant on multivariable analysis. This may suggest a deficiency in the education of the family regarding the diagnosis of cryptorchidism or improper counseling. An area of future improvement is targeting education of the family to ensure full comprehension, especially for those who do not speak English as a primary language at home. It was found that the patient, his family, or another provider who was not their regular PCP was more likely to discover the UDT. This scenario is encountered when a toddler transfers care; the new pediatrician does a complete history and physical examination and discovers the UDT that had remained undiagnosed. Another scenario is when an infant is found to have an undescended testicle on examination but is told to wait by the PCP for more than
one year. These findings indicate a lack of education or failure of complete physical examination by the regular PCP, which is an area of improvement. Targeted intervention toward PCPs has previously been performed with success [22]. A hospital in the UK was able to reduce the median age to surgery for cryptorchidism by 2.5 years with a multimodal quality improvement project [22]. The initial hospital audit between 1992 and 1994 revealed a median age of orchiopexy of 4 years; they identified delayed referral as the major culprit, with 45% of patients who were self-referred after parents noticed the issue. They initiated a mandatory 8-month check by general practitioners (GPs). They disseminated the information to GPs in writing as well as in education events for primary care and hospital staff in 1997. They also made information leaflets for parents and management guidelines for junior pediatric staff. For patients who had UDT at birth, a special written reminder slip was added to the personal child health record at the 8-month tab to prompt the GP to place the referral. With these changes, they were able to reduce their median age of orchiopexy from 4.5 in 1996 to 2.0 in 2001 [22].
380.e5 Table 3
D.D. Jiang et al. Multivariate analysis of variables.
Factors associated with delayed UDT >18 mo (MVA logistic regression results) Clinical variables
Odds ratio
95% CI
P value
Normal birth examination Retractile testicle diagnosis Primary language not English Any potential issues leading to delay Not discovered by the regular PCP
1.9 3.2 2.4 3.6 4.3
1.3e2.7 1.3e7.2 0.5e11.1 1.2e11.0 1.4e13.3
<0.001 0.004 0.268 0.024 0.010
Associated diagnosis of retractile testicle, primary language at home not English, discovery by a new PCP, discovery by someone other than PCP. Statistically significant factors are highlighted in bold. CI, confidence interval; MVA, multivariate analysis; PCP, primary care provider; UDT, undescended testis.
Another important aspect of delay in referral is the possibility of secondary ascent or acquired UDT. Traditionally, this was believed to be a rare occurrence [23]; however, in a large UK prospective study, the incidence of congenital cryptorchidism was 1.6% at 3 months, but the cumulative orchiopexy rate in the country was 3% [24]. Other single-institutional studies also support a significant rate of ascending testes as the explanation for the delay in treatment [25,26]. In a larger retrospective study, the rate of ascended testis was found to be 44% and associated with a history of being retractile [25]. With regard to the study, 39% of the patients had a normal testicular examination at birth. Furthermore, MVA demonstrated that ‘retractile testis’ diagnosis increased the risk of referral delay by approximately 3-fold. These findings are also consistent with a recent review analysis on cryptorchidism [27]. Although strict-protocolled temporal testicular examinations that may provide insight into the true rate of secondary assent were lacking, these findings suggest a significant number of patients can have secondary ascent. Furthermore, it highlights the importance of thorough annual testicular examinations even in patients with previously normal findings. For an ad hoc subanalysis, patients who had a normal testicular examination at birth (n Z 56) were excluded: the median age at the referral visit was 24 months (IQR, 8e72), and 65 patients (53%) were seen after the age of 18 months. For these patients compared with allcomers, the median age at the referral visit decreased by almost half, but more than half the patients still had a delay in referral. These findings highlight that secondary ascent may account for a significant number of delayed orchiopexies, but there are still areas of improvement even when these are excluded from analyses. Twenty-nine percent of patients were identified with either health or social complications that may have led to delay in care. For example, many health concerns affecting the child such as serious cardiopulmonary defects, serious congenital pathologies, and psychiatric problems were identified. Other non-clinically related concerns such as adoption, foster home, lack of insurance, and refugee status contributed to some of the patient delay. These possible reasons of delays were not homogenous. Care for pediatric patients can be challenging; clinicians need to address not only the needs of the patient but also the family’s. There are limitations to this study. The cohort of patients is small, with only 178 patients; it may not be powered to detect subtle differences in factors such as BMI or insurance
that may contribute to delay. In addition, there are other potential factors that may contribute to delay in referral that are not captured including palpable or non-palpable testis, other concurrent genitourinary abnormalities, income, race, and so on. Race was not included in this study because of the lack of diversity in the region, thus making it difficult to be powered appropriately. Another potential source of bias was parents’ recall when documentation of the newborn and subsequent genital examinations was not available. Additionally, a control cohort, such as retractile testicles, was not included to use a comparison. Although this study is limited to just over one year, the reported rates of delayed referral are similar to previously reported rates.
Conclusion Within the tertiary pediatric hospital, 64% of patients who underwent orchiopexy had a delay for the referral visit at age greater than 18 months. This was associated with the diagnosis of ‘retractile testis,’ non-English primary language, and discovery by someone who is not the routine PCP. Secondary ascent may play a significant role, representing up to 39% of cryptorchidism. Future efforts to improve timing of referral are underway.
Author statements Ethical approval The study was approved by the IRB (IRB 000169916).
Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-forprofit sectors.
Competing interests None declared.
Disclaimer The opinions expressed in this article are the authors’ own and do not reflect those of the Doernbecher Children’s Hospital.
Factors associated with delay in undescended testis referral
References [1] Sijstermans K, Hack WW, Meijer RW, et al. The frequency of undescended testis from birth to adulthood: a review. Int J Androl 2008;31:1e11. [2] Buemann B, Henriksen H, Villumsen AL, et al. Incidence of undescended testis in the newborn. Acta Chir Scand Suppl 1961;(Suppl. 283):289e93. [3] Wenzler DL, Bloom DA, Park JM. What is the rate of spontaneous testicular descent in infants with cryptorchidism? J Urol 2004;171:849e51. [4] Taghizadeh AK, Thomas DF. Ascent of the testis revisited: fact not fiction. BJU Int 2008;102:676e8. [5] Pettersson A, Richiardi L, Nordenskjold A, et al. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med 2007;356:1835e41. [6] Walsh TJ, Dall’Era MA, Croughan MS, et al. Prepubertal orchiopexy for cryptorchidism may be associated with lower risk of testicular cancer. J Urol 2007;178:1440e6. discussion 1446. [7] Lee PA. Fertility after cryptorchidism: epidemiology and other outcome studies. Urology 2005;66:427e31. [8] Timing of elective surgery on the genitalia of male children with particular reference to the risks, benefits, and psychological effects of surgery and anesthesia. American Academy of Pediatrics. Pediatrics 1996;97:590e4. [9] Kolon TF, Herndon CD, Baker LA, et al. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol 2014;192: 337e45. [10] Radmayr C, Dogan HS, Hoebeke P, et al. Management of undescended testes: European association of Urology/European Society for Paediatric Urology guidelines. J Pediatr Urol 2016; 12:335e43. [11] 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 2018:736e43. [12] Kokorowski PJ, Routh JC, Graham DA, et al. Variations in timing of surgery among boys who underwent orchidopexy for cryptorchidism. Pediatrics 2010;126:e576e82. [13] Yiee JH, Saigal CS, Lai J, et al. Timing of orchiopexy in the United States: a quality-of-care indicator. Urology 2012;80:1121e6. [14] Bradshaw CJ, Corbet-Burcher G, Hitchcock R. Age at orchidopexy in the UK: has new evidence changed practice? J Pediatr Urol 2014;10:758e62.
380.e6 [15] Bruijnen CJ, Vogels HD, Beasley SW. Age at orchidopexy as an indicator of the quality of regional child health services. J Paediatr Child Health 2012;48:556e9. [16] Hidas G, Ben Chaim J, Udassin R, et al. Timing of orchidopexy for undescended testis in Israel: a quality of care study. Isr Med Assoc J 2016;18:697e700. [17] Wei Y, Wu SD, Wang YC, et al. A 22-year retrospective study: educational update and new referral pattern of age at orchidopexy. BJU Int 2016;118:987e93. [18] Hrivatakis G, Astfalk W, Schmidt A, et al. The timing of surgery for undescended testis e a retrospective multicenter analysis. Dtsch Arztebl Int 2014;111:649e57. [19] Bayne AP, Alonzo DG, Hsieh MH, et al. Impact of anatomical and socioeconomic factors on timing of urological consultation for boys with cryptorchidism. J Urol 2011;186:1601e5. [20] McCabe JE, Kenny SE. Orchidopexy for undescended testis in England: is it evidence based? J Pediatr Surg 2008;43:353e7. [21] Steckler RE, Zaontz MR, Skoog SJ, et al. Cryptorchidism, pediatricians, and family practitioners: patterns of practice and referral. J Pediatr 1995;127:948e51. [22] Brown JJ, Wacogne I, Fleckney S, et al. Achieving early surgery for undescended testes: quality improvement through a multifaceted approach to guideline implementation. Child Care Health Dev 2004;30:97e102. [23] Stec AA, Thomas JC, DeMarco RT, et al. Incidence of testicular ascent in boys with retractile testes. J Urol 2007;178:1722e4. discussion 1724-5. [24] Cryptorchidism: a prospective study of 7500 consecutive male births, 1984-8. John Radcliffe hospital cryptorchidism study Group. Arch Dis Child 1992;67:892e9. [25] Guven A, Kogan BA. Undescended testis in older boys: further evidence that ascending testes are common. J Pediatr Surg 2008;43:1700e4. [26] Gracia J, Navarro E, Guirado F, et al. Spontaneous ascent of the testis. Br J Urol 1997;79:113e5. [27] Thorup J, Cortes D. Surgical management of undescended testis - Timetable and outcome: a debate. Sex Dev 2019.
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jpurol.2019.03.029.