Lactate dehydrogenase, Gleason score and HER-2 overexpression are significant prognostic factors for M1b prostate cancer

Abstract

Abstract. It has not been elucidated whether certain types of M1b prostate cancer (M1b PC) are associated with a poor outcome. The present study retrospectively identified predictive factors related to the outcome of M1b PC. The subjects were 104 patients who attended our hospital and received a diagnosis of M1b PC. The observation period ranged from 4 to 122 months (median, 43 months). The parameters investigated were: T classification, N classification, Gleason score (GS), pretreatment prostate-specific antigen (PSA) level, extent of disease (EOD) grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), calcium, and hemoglobin (Hb) levels, platelet count, and the status of HER-2 overexpression as determined with a Hercep Test™ Kit using initial needle biopsy specimens for diagnosis. Log-rank test and Cox univariate analysis identified the following factors with statistically significant differences: pretreatment PSA ≥192, N1, GS ≥8, EOD grade 3+4, high LDH, high ALP, low Hb, and HER-2 overexpression. Multivariate Cox proportional hazard analysis identified the factors GS ≥8, high LDH, and HER-2 overexpression with significant differences. The hazard ratio was 5.962, 2.465, and 2.907, respectively, and the probability value was P=0.0218, P=0.0207 and P=0.0090, respectively. When the subjects with GS ≥8, high LDH, and HER-2 over-expression were classified as the high-risk group, the 5-year cause-specific survival rate was 51.2, 29.6, and 20.0%, respectively. The present study showed that M1b PC patients with GS ≥8, high LDH, and HER-2 overexpression have a very poor outcome and thus, should be treated as a high-risk group requiring close follow-up. IntroductionOf cancer deaths, in the USA, the incidence of prostate cancer (PC) ranks first in men, while the mortality from PC ranks second after lung cancer. In Europe, about 260,000 people are diagnosed with PC every year (1), and PC accounts for 9% of cancer deaths in men (2). The frequency of PC varies from country to country; it has been reported to be lowest in the Far East, particularly in mainland China and Japan (3). In Japan, however, the frequency in 2015 is expected to increase to about 4.6 times that in 1985 (4), and a recent study reported that PC screening would reduce mortality from PC by 20% (5). PC will thus become an increasingly important disease in men. Patients with PC have only vague symptoms in the early phase of the disease; it is not rare for patients to present with chief complaint of bone pain or neurological symptoms and found to already have PC with bone metastases at the time of diagnosis (6). Most PC is androgen-dependent. Patients with metastatic PC are rarely cured, and most of them are treated by hormone therapy. The majority of such patients, however, progress to castration-resistant prostate cancer (CRPC) within several years. Hormone resistance is considered to be acquired through abnormalities in the androgen receptor as well as a mechanism other than the androgen receptor (7). At present, however, the characteristics of ...

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