Abstract and Introduction
Abstract
A lack of consensus and few data support testosterone replacement therapy (TRT) in hypogonadal men who have been treated for prostate cancer (CaP), particularly those who have received radiation therapy. We performed retrospective review of 13 hypogonadal men with CaP, treated with brachytherapy or external beam radiotherapy who were subsequently treated with testosterone (T) between 2006 and 2011. Serum T, free T (FT), estrogen (E), sex hormone-binding globulin (SHBG), prostate-specific antigen (PSA), hemoglobin (Hgb) and hematocrit (Hct) values were evaluated approximately every 3 months after TRT initiation up to 67 months of follow-up. Prostate biopsies demonstrated four men with Gleason (Gl) 6, 7 with Gl 7 and 2 with Gl 8 disease. Median (interquartile range) age at TRT initiation was 68.0 (62.0–77.0) years, initial T 178.0 (88.0–263.5) ng dl, FT 10.1 (5.7–15.0) pg ml and PSA 0.30 (0.06–0.95) ng ml. Median follow-up after TRT initiation was 29.7 months (range 2.3–67.3 months). At median follow-up, a significant increase in mean T (368.0 (281.3–591.0) ng dl, P=0.012) and SHBG were observed, with no significant increases in Hgb, Hct, E, FT, or PSA (0.66 (0.16–1.35) ng ml, P=0.345). No significant increases in PSA or CaP recurrences were observed at any follow-up interval. TRT in the setting of CaP after treatment with radiation therapy results in a rise in serum T levels and improvement in hypogonadal symptoms without evidence of CaP recurrence or progression.
Introduction
Late-onset hypogonadism (LOH) is present in up to 7% of men <70 years old and in up to 18.4% of men >70 years old. Though men over the age of 65 years currently account for 5.6% of the US population, this age group is growing 2–3 times faster than men <65 years old, suggesting that the prevalence of LOH will only continue to increase. Characterized by low serum testosterone (T), as well as symptoms of androgen deficiency, which include loss of libido, erectile dysfunction, depression, lethargy, concentration difficulties, sleep disturbance, osteoporosis and loss of muscle strength, LOH has widespread implications on men's health and has been associated with cardiovascular disease, insulin resistance, type II diabetes and metabolic syndrome.
Treatment with testosterone replacement therapy (TRT) ameliorates the symptoms of hypogonadism, but is controversial in the setting of prostate cancer (CaP) due to the belief that T can stimulate its growth. A study by Huggins and Hudges in 1941 demonstrated CaP regression in men with metastatic disease after surgical castration and subsequent in vitro studies showed CaP cell growth after treatment with T, further supporting the CaP–androgen relationship. Despite these early findings, there remains a dearth of clinical evidence supporting a link between high serum T and increased CaP risk. Thus, in the light of mounting evidence suggesting worse health outcomes in men diagnosed with hypogonadism, together with the lack of data supporting a clinical association between T and CaP growth, TRT has been initiated in hypogonadal men with CaP.
Most studies examining hypogonadal men receiving TRT after radical prostatectomy (RP) have described no cases of biochemical recurrence or evidence of CaP progression in the setting of localized disease. Similarly, studies of patients with CaP treated with brachytherapy and/or external beam radiotherapy (EBRT) and on TRT have reported transient rises in prostate-specific antigen (PSA), but no patients with CaP recurrence or progression prompting TRT cessation. Furthermore, no evidence of bone metastasis or local recurrence has been observed in hypogonadal patients with locally advanced CaP who underwent surgical castration followed by intermittent TRT, nor have there been significant rises in PSA or evidence of CaP progression in patients with CaP on active surveillance treated with TRT. In one study examining 96 men on TRT after RP, radiation therapy, or intermittent androgen deprivation, with 8 men demonstrating evidence of distant metastasis prior to TRT initiation, TRT was stopped in 60% of men due to rising PSA.
The above small studies overall support the use of TRT in patients with CaP, irrespective of CaP treatment modality, in the setting of vigilant follow-up, as does a recent review of the published literature, particularly given the known effects of exogenous T on prostate cell growth in vitro. However, no published data from randomized controlled trials studying outcomes of TRT in treated CaP patients are currently available, and the data from retrospective studies are limited. In this retrospective study, we assess the efficacy and safety of TRT in a cohort of men with CaP treated with radiation, with the goal of adding to the literature describing TRT in men with CaP.