Outcomes and predictive factors of prostate cancer patients with extremely high prostate-specific antigen level

Abstract

Purpose: Prostate-specific antigen (PSA) is a useful biomarker of prostate cancer (PCa). High-risk localized PCa is defined using T stage, Gleason score (GS), and PSA. However, PSA level defining high-risk PCa is at most 20 ng/mL. In PCa patients with high PSA, it is unclear whether PSA itself can be a prognostic factor.

Methods: Of 642 patients who were diagnosed as PCa, 90 patients with PSA > 100 ng/mL were retrospectively analyzed. Patients were divided into three groups according to PSA level: very high (>1,000 ng/mL), moderately high (200-1,000 ng/mL), and slightly high (100-200 ng/mL).

Results: There were no significant differences in overall survival or PCa-specific survival (PCaSS) among the three groups. Regardless of PSA level, high M stage and GS significantly reduced PCaSS. When the risk classification was made using M stage and GS (high risk = M1 and GS ≥ 9, low risk = M0 and GS < 9, and intermediate risk = others), PCaSS was significantly different among high-, intermediate-, and low-risk groups with 5-year survival rates of 58.2, 80.6, and 100 %, respectively. Although there were no differences in treatment performed during the castration-resistant stage, patients undergoing alternative anti-androgen and zoledronic acid treatment had better PCaSS after being castration-resistant.

Conclusions: As PSA could not be a prognostic factor in PCa patients with high PSA > 100 ng/mL, the novel risk classification using M stage and GS may help clinicians to predict PCaSS and to plan follow-up schedules after diagnosis.

Fig. 1

Cases with PSA > 100 ng/mL. PSA at diagnosis in Case 1 and Case 2 was more than 4,000 and around 100 ng/mL, respectively. Generally, prognosis of Case 1 with higher T and N stage than Case 2 seemed to be worse than that of Case 2. However, survival time of Case 1 was much longer than that of Case 2. CAB combined androgen blockade, ZOL zoledronic acid, AA anti-androgen, EMP estramustine phosphate

Fig. 2

OS and PCaSS in overall patients. Five-year survival rates of OS and PCaSS were 72.2 and 79.1 %, respectively, and 10-year survival rates were 51.5 and 67.7 %, respectively

Fig. 3

OS, PCaSS, and CFS in VH, MH, and SH. Based on PSA at diagnosis, patients were divided into very high (VH, >1,000 ng/mL, n = 21), moderately high (MH, 200–1,000 ng/mL, n = 37), and slightly high (SH, 100–200 ng/mL, n = 32) groups. However, there were no significant differences in OS, PCaSS, or CFS among VH, MH, and SH groups (p = 0.2381, p = 0.7742, and p = 0.1909, respectively)

Fig. 4

OS and PCaSS according to T, N, and M stage and GS. T, N, and M stage and GS were examined to determine whether they can be used as prognostic factors in patients with PSA > 100 ng/mL. There were no differences in OS or PCaSS among each T and N stage (p = 0.0535 and p = 0.2884 with T stage, respectively, and p = 0.2381 and p = 0.1530 with N stage, respectively). On the other hand, there were significant differences in both OS and PCaSS among each M stage (p = 0.0075 and p = 0.0048, respectively). GS could not predict OS (p = 0.1273). However, there were significant differences in PCaSS among each GS group (p = 0.0166)

Fig. 5

Novel risk classification of PCa with PSA > 100 ng/mL. High risk was defined as M1 and GS ≥ 9, low risk was defined as M0 and GS < 9, and intermediate risk was defined as neither high nor low risk. The numbers of patients in the high-, intermediate-, and low-risk groups were 32, 36, and 21, respectively. PCaSS was clearly distinguished according to risk, and this risk classification showed better prediction of PCaSS than using M stage or GS alone (p = 0.0039). Five-year survival rates in high-, intermediate-, and low-risk groups were 58.2, 80.6, and 100 %, respectively, and 10-year survival rates were 29.1, 80.6, and 92.3 %, respectively

Fig. 6

Treatments performed and PCaSS after being CRPC. Although docetaxel (DTX), estramustine phosphate (EMP), and ethinylestradiol (EE) did not improve PCaSS (p = 0.9936, p = 0.3699, and p = 0.4685, respectively), patients who underwent alternative anti-androgen (AA) and zoledronic acid (ZOL) therapy had significantly better PCaSS after being CRPC than those who did not (p = 0.0088 and p = 0.0137). However, ZOL did not improve PCaSS from the time of diagnosis (p = 0.1092)