We identified men who underwent orchiopexy for undescended testis in Sweden between 1964 and 1999. Cohort subjects were identified in the Swedish Hospital Discharge Register and followed for the occurrence of testicular cancer through the Swedish Cancer Registry. Vital statistics and data on migration status were taken from the Register of Population and Population Changes for the years 1965 through 2000. We estimated the relative risk of testicular cancer using Poisson regression of standardized incidence ratios, comparing the risk in the cohort with that in the general population. We also analyzed the data by means of Cox regression, using internal comparison groups. Results The cohort consisted of 16,983 men who were surgically treated for undescended testis and followed for a total of 209,984 person-years. We identified 56 cases of testicular cancer during follow-up. The relative risk of testicular cancer among those who underwent orchiopexy before reaching 13 years of age was 2.23 (95% confidence interval [CI], 1.58 to 3.06), as compared with the Swedish general population; for those treated at 13 years of age or older, the relative risk was 5.40 (95% CI, 3.20 to 8.53). The effect of age at orchiopexy on the risk of testicular cancer was similar in comparisons within the cohort. Conclusions Treatment for undescended testis before puberty decreases the risk of testicular cancer.

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Age at Surgery for Undescended Testis and Risk of Testicular Cancer

I. Normal Development A. Anatomical aspects 1. Sexual development 2. The gubernaculum 3. Cranial suspensory ligament 4. Abdominal pressure B. Hormonal control and functional aspects of testicular descent 1. Mullerian inhibiting substance 2. Androgen 3. The genitofemoral nerve (GFN) 4. Calcitonin gene-related peptide (CGRP) II. Cryptorchidism A. Etiology B. Frequency C. Are some UDT acquired? D. Risks of infertility/malignancy E. Role of hormone therapy F. Timing of surgery

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Anatomical and functional aspects of testicular descent and cryptorchidism.

Objective : To determine the risk of testicular cancer associated with undescended testis, inguinal hernia, age at puberty, marital status, infertility, vasectomy, and amount of exercise. Design : A population based case-control study with a questionnaire administered by an interviewer and with relevant supplementary data extracted from general practioners9 notes. Setting : Nine health regions within England and Wales. Subjects : 794 men, aged 15-49 years, with a testicular germ cell tumour diagnosed between 1 January 1984 and 1 January 1987; each had an age matched (within one year) control selected from the list of their general practioner. Results : There was a significant association of testicular cancer with undescended testis (odds ratio 3.82; 95% confidence interval 2.24 to 6.52) and inguinal hernia (1.91; 1.12 to 3.23). The excess risk associated with undescended testis was eliminated in men who had had an orchidopexy before the age of 10 years. There were positive associations with earl age at voice breaking, early age at starting to shave, and infertility. There was a significant association with a sedentary lifestyle and a moderate protective effect of exercise. There was no association with vasectomy. Conclusion : This study confirms previous reports that developmental urogenital abnormalities result in an increased risk of testicular cancer. The trend to perform orchidopexy at younger ages may reduce the risk associated with undescended testis. The increased risks associated with early age at puberty and low amounts of exercise may be related to effects of exposure to endogenous hormones. Changes in both of these factors may partly contribute to the increasing rates of testicular cancer observed in the past few decades.

Aetiology of testicular cancer: association with congenital abnormalities, age at puberty, infertility, and exercise

52. Berger RE. Epididymitis. In: Holmes KK, Mardh PA, Sparling PF et al. (eds). Sexually Transmitted Diseases. New York: McGraw-Hill, 1984, pp. 650-662. 53. Weidner W, Schiefer HG, Garbe C. Acute nongonococcal epididymitis. Aetiological and therapeutic aspects. Drugs 1987;34 (Suppl 1):111-117. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3481311&do

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Guidelines on Male Infertility

Objective: To determine the risk of testicular cancer in relation to undescended testis and its treatment based on recorded details of the maldescent, treatment, and biopsy from case notes. Design: Cohort study. Setting: Hospital for Sick Children, Great Ormond Street, London. Subjects: 1075 boys with cryptorchidism treated by orchidopexy or hormones at the hospital during 1951-64. Main outcome measures: Relative risk of testicular cancer in the cohort compared with men in the general population. Results: 12 testicular cancers occurred in 11 of the patients during follow up to mid-1990 (relative risk of cancer in males with cryptorchidism=7.5 (95% confidence interval 3.9 to 12.8)). The relative risk fell significantly beyond 15 years after orchidopexy but did not decrease with younger age at orchidopexy. Risk was significantly raised in testes that had had biopsy samples removed during orchidopexy (relative risk=66.7 (23.9 to 143.3) compared with a testis in a man in the general population) and was significantly greater in these testes than in undescended testes that had not had biopsy samples taken at orchidopexy (6.7 (2.7 to 13.5)). No reasons for biopsy or distinguishing clinical aspects of the testes that had had biopsy samples taken and later developed malignancies were evident in the case notes. No histological abnormalities were evident at initial biopsy except in one testis that had features of dysgenesis. Conclusions: Biopsy seems to be a stronger risk factor for testicular cancer than any factor previously identified. The trauma of open biopsy may contribute substantially to risk of malignancy or the testes may have been selected for biopsy on the basis of clinical factors predictive of malignancy but not mentioned in the case notes. Key messages The reasons for increased risk of testicular cancer in cryptorchidism are unclear Risk of testicular cancer was determined in follow up of 1075 boys with cryptorchidism treated during 1951-64 The relative risk of testicular cancer in the cohort compared with men in the general population was 7.5 and did not decrease with younger age at orchidopexy Risk was much greater in undescended testes from which a biopsy sample had been taken during orchidopexy than in those with no biopsy Biopsy was a stronger risk factor for testicular cancer than any factor previously identified

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M.J. Peckham

Papers

Effect of age at orchidopexy on risk of testicular cancer

Effect of Age at Orchidopexy on Risk of Testicular Cancer