Testicular Function After Radiotherapy for Rectal Cancer—A Review

Abstract

Introduction Eighty percent of all male rectal cancer patients are sexually active at the time of diagnosis. Because of modern multimodal therapy many can expect long-term survival. The testes can be exposed to scattered or direct radiation during radiotherapy, depending on their position in relation to the targeted volume. Aim This review analyzes the current literature providing data on testicular exposure to radiation during radiotherapy for rectal cancer and the consequences on testicular function. Methods A systematic search was conducted in PubMed, Embase, and Cochrane. Ten original articles providing data on testicular exposure to radiation and testicular function in men with primary rectal cancer were included for qualitative synthesis. Main Outcome Measures Data on testicular exposure to radiation and testosterone levels in men with rectal cancer are reported. Results On average, the testes were exposed to 0.24–8.4 Gy during long-course radiotherapy for rectal cancer. Testosterone levels after radiation were significantly lower compared with pretreatment levels or compared with patients treated with surgery alone. After radiotherapy, the absolute risk increase was 0.17–0.30 for posttreatment testosterone levels below 8 nmol/L. In the largest study, the relative risk was 2.7 for testosterone levels below 8 nmol/L for men treated with radiotherapy compared with men treated with surgery alone. Conclusion Current data generate three hypotheses: (i) during long-course radiotherapy for rectal cancer, the testes can be exposed to direct and/or scattered radiation; (ii) men treated with radiotherapy seem at risk to develop testicular dysfunction with decreased serum testosterone levels compared with both pretreatment values and men treated with surgery alone; and (iii) a decrease in testosterone levels (<8 nmol/L) may precipitate specific symptoms caused by testosterone deficiency such as impaired physical, psychological, and sexual function after treatment.

Assessment of testicular dose during preoperative radiotherapy for rectal cancer

“…Cross-sectional and longitudinal studies also describe a negative impact of RT on Leydig cell function [4][5][6][7][8]. According to a systematic review the average cumulative testicular dose (TD) during long course external beam RT varies between 1.24 Gy and 8.4 Gy, mainly depending on the distance between the testes and the target volume [9]. These findings were confirmed among 83 men treated with long course RT (50.4 Gy) and concomitant chemotherapy [10].…”

“…The average planned mTD corresponds to 5.0% of the prescribed dose during short course RT and 3.5% of the prescribed dose during long course RT. This is a low proportion compared to the testicular exposure reported with 3-17% of the prescribed dose in a systematic review that summarises TDs during RT for rectal cancer assessed with scrotal dosimeters, TPS or equations based on phantom measurements [9]. The difference between short and long course RT in the proportion of prescribed dose in average absorbed by the testes is most likely due to the skewed distribution of mTD.…”

“…Historical studies in men irradiated for Hodgkin's lymphoma and testicular seminoma report a high risk of permanent azoospermia if TD exceeds 1.2-1.4 Gy during a fractionated RT regimen [19,20]. The radiation tolerance of Leydig cells seems to be higher but a negative impact on Leydig cell function has to be expected in selected individuals treated with multimodal therapy for rectal cancer [9]. So far a dose-response relationship between the TD and the longitudinal changes in serum testosterone levels has not been established [10].…”

Risk of second primary cancer in patients treated with radiotherapy for rectal cancer

“…Radiation towards the rectal cancer may synchronously cure an occult prostate cancer. In addition, radiation may have a hormonal impact owing to a scattered radiation dose to the testicles that may be sufficient to lower testosterone levels and thereby impede the development of prostate cancer 26 . This beneficial effect of radiation was also noted in a study 27 investigating the association between colorectal and prostate cancers.…”

Hypogonadism in young men treated for cancer

“…The available data indicate approximately 3 times increased risk of subnormal testosterone levels in RC patients given irradiation as compared to those treated with surgery only. 32,33 Another relatively large group of young cancer survivors, in whom the issue of Leydig cell dysfunction may become a clinical problem, are those with hematological malignancies. Following non-myeloablative bone marrow transplantation, sustained severe damage to the Leydig cells was observed.…”