Low pretreatment serum total testosterone is associated with a high incidence of Gleason score 8–10 disease in prostatectomy specimens: data from ethnic Chinese patients with localized prostate cancer

Abstract

Study Type – Prognosis (prospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Previous data from clinically localized prostate cancer (PCa) series treated with radical prostatectomy (RP) have suggested that low preoperative serum total testosterone level is associated with more aggressive PCa; however, the definition of low preoperative total testosterone level varied among these studies (from 220 ng/dL to 387 ng/dL). Moreover, no relevant data exist in the literature regarding ethnic Chinese patients. The study shows that the most widely used threshold for low pretreatment total testosterone level (total testosterone < 300 ng/dL) is not appropriate for ethnic Chinese patients, because it could not distinguish patients with more aggressive PCa from those with less aggressive disease. Setting the threshold at the level of total testosterone < 250 ng/dL works better, because pretreatment total testosterone < 250 ng/dL is associated with a significantly higher incidence of Gleason score 8–10 disease in RP specimens. OBJECTIVE To investigate the relationship between preoperative serum total testosterone level and prognostic factors of Chinese patients with clinically localized prostate cancer (PCa). PATIENTS AND METHODS A total of 110 patients with localized PCa, treated by radical prostatectomy (RP), were included in this prospective study. Clinical and pathological data from each patient were collected. Total testosterone was measured on the morning of surgery. Total testosterone levels for each patient were compared using two thresholds: threshold 1 (total testosterone <300 ng/dL vs total testosterone ≥300 ng/dL) and threshold 2 (total testosterone <250 ng/dL vs total testosterone ≥250 ng/dL). RESULTS The median preoperative total testosterone level was 346 ng/dL. Gleason scores of ≤6, 7 and ≥8 were found in the RP specimens from 21 (19.1%), 67 (60.9%) and 22 (20.0%) patients, respectively. Compared with those with low grade disease, patients with high grade disease (Gleason score ≥ 8) in RP specimens had a significantly lower preoperative total testosterone. When comparing 35 patients with hypogonadism with 75 patients with eugonadism, classified by threshold 1, no significant relationships were found. When comparing 18 patients with hypogonadism with 92 patients with eugonadism, classified by threshold 2, pathological Gleason score ≥ 8 tumours were more common in patients with hypogonadism. CONCLUSION Setting the threshold for hypogonadism at the level of pretreatment serum total testosterone <250 ng/dL is appropriate for ethnic Chinese patients with localized PCa, because patients with pretreatment total testosterone <250 ng/dL are associated with a higher incidence of Gleason score 8–10 disease in RP specimens.

Low serum testosterone is associated with tumor aggressiveness and poor prognosis in prostate cancer

“…The present study demonstrated that, compared with high levels of total serum testosterone at the time of diagnosis, low total serum testosterone levels at the time of diagnosis were associated with aggressive features of PCa, which is consistent with the results of previous studies (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). A previous pooled analysis of 18 prospective studies identified that pre-diagnosis serum testosterone levels were not associated with the high-risk form of PCa (32); however, the testosterone levels in this analysis were measured years prior to PCa diagnosis and a different definition of high-risk form of PCa was used.…”

“…However, studies on the association between testosterone and PCa risk have produced conflicting results (8,9). Numerous studies have demonstrated that low, rather than high, testosterone levels at diagnosis were associated with various markers of poor prognosis, including an advanced pathological stage, higher Gleason scores, higher PSA levels, seminal vesicle invasion and positive surgical margins (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Few studies have further investigated whether low levels of testosterone predict poor prognosis.…”

Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer

“…20 Park et al 9 demonstrated a correlation between hypogonadism and unfavorable outcomes in prostatic biopsies, such as increased incidence of GS ≥ 8. Several studies, despite adopting different thresholds for the definition of hypogonadism, have confirmed an association between low testosterone levels and adverse characteristics and outcomes for PCa, including higher Gleason score, 21,22 higher pathological stage 10,22 and increased risk for disease progression. 23 However, a number of investigations failed to show an association between low serum testosterone levels and high-risk characteristics of PCa specimens.…”

Testosterone and prostate cancer: an evidence-based review of pathogenesis and oncologic risk

“…Men with Gleason 8 or greater had significantly lower serum testosterone, 14.2 nmol/l (410 ng/dl) versus 11.1 nmol/l (320 ng/dl) (p = 0.028). Furthermore, hypogonadal men, with total morning testosterone <8.6 nmol/l (250 ng/dl), were more likely to have Gleason 8 or greater disease (p = 0.005) [Dai et al 2012].…”