Abstract
To evaluate the prognostic significance of prostate-specific antigen (PSA) decline depth and duration in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC) undergoing abiraterone treatment. We retrospectively analyzed data from 153 high-risk patients with mHSPC receiving first-line abiraterone therapy. Patients were stratified based on PSA dynamics during treatment. Kaplan–Meier survival analysis and Cox proportional hazards regression were used to assess the associations between PSA decline patterns, PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). Among the 153 patients, 85 exhibited PSA nadir <0.2 ng ml−1, 48 had PSA nadir level ranging from 0.2 ng ml−1 to 4 ng ml−1, and 20 presented with a PSA nadir >4 ng ml−1. During abiraterone treatment, PSA nadir <0.2 ng ml−1 was significantly associated with improved median PSA-PFS (51.0 months vs 18.5 months vs 6.9 months, P < 0.0001), median rPFS (52.0 months vs 24.3 months vs 10.3 months, P < 0.0001), and median OS (not reached vs 48.5 months vs 28.1 months, P < 0.0001) compared with PSA nadir ≥0.2 ng ml-1 and <4 ng ml-1, and PSA nadir ≥4 ng ml-1. In the cohort with PSA nadir <0.2 ng ml−1, achieving PSA <0.2 ng ml−1 within 6 months and maintaining this level for over 10 months significantly enhanced clinical outcomes, as evidenced by median PSA-PFS (not reached vs 26.9 months, P < 0.0001), median rPFS (not reached vs 27.5 months, P < 0.0001), and median OS (not reached vs 44.4 months, P < 0.0001). Cox regression analysis revealed that achieving PSA <0.2 ng ml−1 within 6 months post-treatment and sustaining this level for over 10 months are independent prognostic factors. In high-risk patients with mHSPC receiving first-line abiraterone, sustained PSA suppression is a key indicator of therapeutic response. The rate, depth, and duration of PSA decline are critical prognostic factors.
Keywords: dynamics, high-risk, prognostic, prostate cancer, PSA
INTRODUCTION
Prostate cancer is among the most prevalent malignant tumors of the male genitourinary system. Globally, it ranks first in incidence and second in mortality among male malignancies, with both rates rising annually.1 Due to the absence of early screening, approximately 54% of patients are diagnosed at the metastatic hormone-sensitive prostate cancer (mHSPC) stage.2,3 Compared with localized disease, metastatic prostate cancer is associated with a twofold reduction in progression-free survival (PFS), and its 5-year relative survival rate declines from 80% to 30%.4,5 Advances in prostate cancer therapeutics and clinical trials have demonstrated the benefits of combining abiraterone or other novel endocrine therapies with androgen deprivation therapy (ADT) across various stages of mHSPC.6,7
The LATITUDE study established the significant overall survival (OS) and PFS benefits of abiraterone in high-risk mHSPC.4 A subsequent analysis revealed that in 45% of abiraterone-treated patients, prostate-specific antigen (PSA) levels did not decline to an undetectable nadir (PSA <0.2 ng ml−1), and these patients had significantly poorer survival outcomes.8 Additionally, previous studies have suggested that the depth of PSA decline and the hemoglobin-to-neutrophil ratio are effective predictors of survival in abiraterone-treated patients.9,10 PSA depth decline has also been identified as a reliable prognostic marker in patients with mHSPC receiving apalutamide and rezvilutamide.11,12,13 However, in certain high-risk patients, deep PSA declines are not sustained and are followed by a rapid transition to metastatic castration-resistant prostate cancer (mCRPC). This suggests that the duration of a deep PSA decline may also be a critical determinant of patient prognosis.
Consequently, this research aimed to explore the prognostic significance of deep PSA decline and its duration in patients treated with abiraterone for high-risk mHSPC.
PATIENTS AND METHODS
Study design
We conducted a retrospective analysis of data from 153 patients diagnosed with high-risk mHSPC at West China Hospital, Sichuan University (Chengdu, China), between September 2012 and June 2023. All patients received first-line ADT (goserelin 10.8 mg every 3 months) and abiraterone (abiraterone 1000 mg per day plus prednisone 10 mg per day). The primary inclusion criteria were as follows: (1) age ≥18 years; (2) prostate cancer diagnosis confirmed through biopsy; (3) presence of distant metastases confirmed by pathology or imaging at the initial diagnosis; and (4) classification as high-risk disease according to the LATITUDE study criteria. The specific standards include at least two of the following criteria: (i) Gleason score ≥8, (ii) bone scan indicating more than three metastases, or (iii) measurable visceral metastases excluding lymph nodes.4 Tumor volume was classified based on the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) criteria, which define high-volume disease as follows: (1) four or more bone metastases on a bone scan, with at least one located outside the vertebral bodies or pelvis, and/or (2) presence of visceral metastases.14
For all high-risk mHSPC cases, we systematically collected the following baseline data: age, International Society of Urological Pathology (ISUP) grade, bone and organ metastasis status, serum PSA levels, hemoglobin (HGB) levels, lactate dehydrogenase (LDH) levels, and alkaline phosphatase (ALP) levels. PSA levels and imaging findings were monitored every 1–3 months throughout the treatment. The study was approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University. The Institutional Review Board (IRB) in West China Hospital approved this study (Approval No. 2022297). We obtained the informed consent of all participants involved in the study.
Primary endpoint
The primary endpoints were PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). PSA-PFS was defined as the duration from treatment initiation to PSA progression, determined using the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria,15 which require a PSA increase of ≥25% from baseline and a PSA level of ≥0.2 ng ml−1, confirmed through reassessment at least 3 weeks later. rPFS was defined as the duration from treatment initiation to radiographic progression or death from any cause. Radiographic progression included primary tumor progression, regional lymph node involvement, soft tissue metastases, and bone metastasis progression, assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.116 and PCWG3 criteria.15 OS was defined as the duration from treatment initiation to death from any cause. PSA response was defined as the maximum reduction in PSA levels from baseline following abiraterone treatment. Rapid and sustained PSA response was defined as achieving a PSA level of <0.2 ng ml−1 within 6 months and maintaining this level for more than 10 months.
Statistical analyses
Baseline characteristics were analyzed using the Chi-square (χ²) test. Kaplan–Meier curves and log-rank tests were used to compare PSA-PFS, rPFS, and OS. Univariate Cox regression analysis was performed to assess the predictive value of each factor for PSA-PFS, rPFS, and OS. Factors with P < 0.05 in univariate analysis were further evaluated using multivariate methods. Statistical analyses were conducted using GraphPad Prism version 8.0.1 (Dotmatics, Boston, MA, USA), SPSS version 26.0 (IBM SPSS Inc., Chicago, IL, USA), and R software version 4.1.0 (R Core Team 2021, Vienna, Austria). Statistical significance was set at P < 0.05.
RESULTS
Characteristics of enrolled patients
This study included 153 patients, and their baseline characteristics are summarized in Table 1. The median follow-up time for the total cohort was 31.3 months. During first-line abiraterone therapy, 85 (55.6%) patients achieved a PSA nadir <0.2 ng ml−1, whereas 68 (44.4%) patients had a PSA nadir ≥0.2 ng ml−1. At the end of follow-up, metastatic PSA-PFS (mPSA-PFS), metastatic rPFS (mrPFS), and metastatic OS (mOS) were 31.0 months, 31.9 months, and not reached (NR), respectively. Among patients with a PSA nadir <0.2 ng ml−1, 60 (70.6%) patients maintained PSA <0.2 ng ml−1 for >10 months. Additionally, 65 patients achieved PSA <0.2 ng ml−1 within 6 months, of whom 48 (73.8%) maintained this level for >10 months, whereas 17 (26.2%) patients had a duration of <10 months. After 6 months of treatment, 116 (75.8%) patients exhibited a PSA response rate ≥90%. A PSA nadir <0.2 ng ml−1 was associated with younger age (age <75 years vs ≥75 years: 60/85 [70.6%] vs 36/68 [52.9%], P = 0.025) and higher HGB (HGB ≥120 g l−1 vs <120 g l-1: 63/85 [74.1%] vs 36/68 [52.9%], P = 0.006).
Table 1.
Baseline characteristics of included high-risk metastatic hormone-sensitive prostate cancer patients receiving abiraterone therapy
| Feature | All (n=153) | PSA nadir <0.2 ng ml−1 (n=85) | PSA nadir ≥0.2 ng ml−1 (n=68) | P |
|---|---|---|---|---|
| Baseline PSA (ng ml−1) | 0.401 | |||
| ≥50, n (%) | 106 (69.3) | 58 (68.2) | 48 (70.6) | |
| <50, n (%) | 30 (19.6) | 19 (22.3) | 11 (16.2) | |
| NA | 17 (11.1) | 8 (9.5) | 9 (13.2) | |
| Age (year) | 0.025* | |||
| ≥75, n (%) | 57 (37.3) | 25 (29.4) | 32 (47.1) | |
| <75, n (%) | 96 (62.7) | 60 (70.6) | 36 (52.9) | |
| ISUP grade | 0.515 | |||
| ≤4, n (%) | 45 (29.5) | 27 (31.8) | 18 (26.5) | |
| 5, n (%) | 96 (62.7) | 52 (61.2) | 44 (64.7) | |
| NA, n (%) | 12 (7.8) | 6 (7.0) | 6 (8.8) | |
| Baseline HGB (g l−1) | 0.006* | |||
| <120, n (%) | 54 (35.3) | 22 (25.9) | 32 (47.1) | |
| ≥120, n (%) | 99 (64.7) | 63 (74.1) | 36 (52.9) | |
| Baseline LDH (U l−1) | 0.353 | |||
| ≥222, n (%) | 37 (24.2) | 23 (27.1) | 14 (20.6) | |
| <222, n (%) | 116 (75.8) | 62 (72.9) | 54 (79.4) | |
| Baseline ALP (U l−1) | 0.206 | |||
| ≥322, n (%) | 17 (11.1) | 7 (8.2) | 10 (14.7) | |
| <322, n (%) | 136 (88.9) | 78 (91.8) | 58 (85.3) | |
| Lymph node metastasis | 0.640 | |||
| Yes, n (%) | 48 (31.4) | 28 (32.9) | 20 (29.4) | |
| No, n (%) | 105 (68.6) | 57 (67.1) | 48 (70.6) | |
| Visceral metastasis | 0.696 | |||
| Yes, n (%) | 25 (16.3) | 13 (15.3) | 12 (17.6) | |
| No, n (%) | 128 (83.7) | 72 (84.7) | 56 (82.4) | |
| Bone metastases ≥4 and axial bone metastasis | 0.413 | |||
| Yes, n (%) | 105 (68.6) | 56 (65.9) | 49 (72.1) | |
| No, n (%) | 48 (31.4) | 29 (34.1) | 19 (27.9) | |
| High-volume tumor | 0.875 | |||
| Yes, n (%) | 107 (69.9) | 59 (69.4) | 48 (70.6) | |
| No, n (%) | 46 (30.1) | 26 (30.6) | 20 (29.4) |
*P<0.05. ALP: alkaline phosphatase; HGB: hemoglobin; ISUP: International Society of Urological Pathology; LDH: lactate dehydrogenase; PSA: prostate-specific antigen
The prognostic value of PSA response in patients treated with abiraterone
Among the 153 patients treated, 85 exhibited PSA nadir <0.2 ng ml−1, 48 had PSA nadir level ranging from 0.2 ng ml−1 to 4 ng ml−1, and 20 presented with a PSA nadir >4 ng ml−1. During abiraterone treatment, PSA nadir <0.2 ng ml−1 was significantly associated with improved mPSA-PFS (51.0 months vs 18.5 months vs 6.9 months, P < 0.0001), mrPFS (52.0 months vs 24.3 months vs 10.3 months, P < 0.0001), and mOS (NR vs 48.5 months vs 28.1 months, P < 0.0001; Figure 1a–1c) compared with PSA nadir ≥0.2 ng ml-1 and <4 ng ml-1, and PSA nadir ≥4 ng ml-1. PSA response rate ≥90% was correlated with improved mPSA-PFS (43.2 months vs 23.4 months vs 11.7 months, P < 0.0001), mrPFS (45.5 months vs 24.3 months vs 10.3 months, P < 0.0001), and mOS (NR vs 40.6 months vs 27.7 months, P < 0.0001; Figure 1d–1f) compared with PSA response rate ≥50% and <90%, and PSA response rate <50%. Abiraterone therapy in patients with a baseline PSA <80 ng ml−1 was associated with a significant improvement in survival compared with a baseline PSA ≥80 ng ml−1 (mPSA-PFS: 43.1 months vs 26 months, P = 0.01; mrPFS: 48.6 months vs 27.5 months, P = 0.01; mOS: NR vs 43.8 months, P = 0.01; Figure 2a–2c).
Figure 1.
The predictive value of PSA nadir and PSA response in high-risk mHSPC patients treated with abiraterone. Kaplan–Meier curves of (a) PSA-PFS, (b) rPFS, and (c) OS of patients with different PSA nadir. Kaplan–Meier curves of (d) PSA-PFS, (e) rPFS, and (f) OS of patients with different PSA response rates. PSA: prostate-specific antigen; mHSPC: metastatic hormone-sensitive prostate cancer; PSA-PFS: PSA progression-free survival; rPFS: radiographic progression-free survival; OS: overall survival.
Figure 2.
The impact of baseline PSA levels on prognosis in high-risk mHSPC patients treated with abiraterone. Kaplan–Meier curves of (a) PSA-PFS, (b) rPFS, and (c) OS of patients with PSA ≥80 ng ml−1 and with PSA <80 ng ml−1. PSA: prostate-specific antigen; mHSPC: metastatic hormone-sensitive prostate cancer; PSA-PFS: PSA progression-free survival; rPFS: radiographic progression-free survival; OS: overall survival.
In the cohort with PSA nadir <0.2 ng ml−1, patients who achieved PSA<0.2 ng ml−1 within 6 months demonstrated prolonged mPSA-PFS (NR vs 31.7 months, P = 0.03) and mrPFS (NR vs 32.6 months, P = 0.01; compared with achieved PSA<0.2 ng ml−1 over 6 months; Supplement Figure 1 (58.1KB, tif) ). A PSA <0.2 ng ml−1 maintained for >10 months was determined as the optimal cut-off, as the prognostic difference was greatest at this point. Achieving and maintaining PSA <0.2 ng ml−1 for ≥10 months significantly improved outcomes, with mPSA-PFS (56.7 months vs 19.3 months, P < 0.0001), mrPFS (56.7 months vs 19.8 months, P < 0.0001), and mOS (NR months vs 40.7 months, P < 0.0001) compared with achieving and maintaining PSA <0.2 ng ml−1 for <10 months, as shown in Figure 3a–3c. Meanwhile, patients with PSA <0.2 ng ml−1 for >10 months had a better prognosis than those with PSA ≥0.2 ng ml−1 and <4 ng ml−1 for the same duration (mPSA-PFS: 56.8 months vs 33.1 months, P = 0.0002; mrPFS: NR vs 33.6 months, P = 0.0002; mOS: NR vs 54.6 months, P = 0.04; Supplement Figure 2 (59.9KB, tif) ). Subgroup analyses showed that achieving PSA <0.2 ng ml−1 within 6 months and maintaining this level for >10 months was significantly associated with better survival outcomes (mPSA-PFS: NR vs 26.9 months, P < 0.0001; mrPFS: NR vs 27.5 months, P < 0.0001; mOS: NR vs 44.4 months, P = 0.001; Figure 4a–4c).
Figure 3.
The impact of PSA <0.2 ng ml−1 duration on prognosis in high-risk mHSPC patients treated with abiraterone. Kaplan–Meier curves of (a) PSA-PFS, (b) rPFS, and (c) OS of patients with ≥10 months and <10 months. PSA: prostate-specific antigen; mHSPC: metastatic hormone-sensitive prostate cancer; PSA-PFS: PSA progression-free survival; rPFS: radiographic progression-free survival; OS: overall survival.
Figure 4.
The impact of rapid and sustained PSA response on prognosis in high-risk mHSPC patients treated with abiraterone. Kaplan–Meier curves of (a) PSA-PFS, (b) rPFS, and (c) OS. Rapid and sustained PSA response: achieving PSA <0.2 ng ml−1 within 6 months and maintaining this level for over 10 months. PSA: prostate-specific antigen; mHSPC: metastatic hormone-sensitive prostate cancer; PSA-PFS: PSA progression-free survival; rPFS: radiographic progression-free survival; OS: overall survival.
In Cox regression analyses, univariate analysis showed that intraductal carcinoma of the prostate (IDCP) positivity was correlated with shorter rPFS and OS, whereas HGB <120 g l−1 was associated with worse PSA-PFS and OS. Additionally, age ≥75 years was linked to shorter OS. Conversely, PSA <20 ng ml−1, PSA <0.2 ng ml−1 maintained for ≥10 months, and a rapid and sustained PSA response were associated with prolonged PSA-PFS, rPFS, and OS. Multivariate analysis confirmed that PSA <0.2 ng ml−1 maintained for ≥10 months and a rapid and sustained PSA response were independent prognostic factors (Table 2).
Table 2.
Univariate and multivariate analyses of each factor’s value in predicting PSA-PFS, rPFS, and OS of the abiraterone treatment in the cohort with PSA nadir <0.2 ng ml−1
| Characteristic | PSA-PFS | rPFS | OS | |||
|---|---|---|---|---|---|---|
|
|
|
|
||||
| Univariable analysis, HR (95% CI), P | Multivariable analysis, HR (95% CI), P | Univariable analysis, HR (95% CI), P | Multivariable analysis, HR (95% CI), P | Univariable analysis, HR (95% CI), P | Multivariable analysis, HR (95% CI), P | |
| Baseline PSA (ng ml−1) | ||||||
| <20 vs ≥20 | 0.28 (0.11–0.69), 0.006* | 0.28 (0.10–0.80), 0.018* | 0.23 (0.09–0.59), 0.002* | 0.27 (0.09–0.88), 0.029* | 0.12 (0.04–0.39), <0.001* | 0.26 (0.06–1.15), 0.076 |
| <50 vs ≥50 | 0.58 (0.27–1.24), 0.163 | 0.64 (0.28–1.47), 0.289 | 0.34 (0.11–1.06), 0.062 | |||
| <100 vs ≥100 | 1.16 (0.56–2.40), 0.694 | 0.85 (0.39–1.85), 0.680 | 0.38 (0.11–1.28), 0.119 | |||
| Age (year) | ||||||
| ≥75 vs <75 | 1.73 (0.84–3.55), 0.135 | 1.84 (0.86–3.92), 0.114 | 3.96 (1.30–12.07), 0.015* | 6.94 (1.50–32.20), 0.013* | ||
| Baseline HGB (g l−1) | ||||||
| <120 vs ≥120 | 4.52 (1.80–11.35), 0.001* | 0.78 (0.27–2.22), 0.636 | 4.43 (1.63–12.04), 0.004* | 1.68 (0.50–5.61), 0.399 | 5.88 (1.51–22.93), 0.011* | 2.24 (0.38–13.36), 0.375 |
| Baseline LDH (U l−1) | ||||||
| ≥222 vs <222 | 1.44 (0.71–2.92), 0.317 | 1.81 (0.86–3.81), 0.120 | 2.88 (0.91–9.11), 0.072 | |||
| Baseline ALP (U l−1) | ||||||
| ≥322 vs <322 | 1.18 (0.41–3.37), 0.764 | 1.78 (0.67–4.72), 0.249 | 0.62 (0.08–4.88), 0.653 | |||
| Lymph node metastasis | ||||||
| With vs without | 1.77 (0.90–3.51), 0.099 | 1.79 (0.86–3.70), 0.119 | 1.15 (0.37–3.55), 0.804 | |||
| Visceral metastasis | ||||||
| With vs without | 1.71 (0.70–4.19), 0.242 | 1.76 (0.66–4.66), 0.258 | 2.53 (0.77–8.29), 0.126 | |||
| Bone metastases ≥4 and axial bone metastasis | ||||||
| Yes vs no | 1.25 (0.58–2.70), 0.565 | 1.77 (0.72–4.34), 0.214 | 0.61 (0.20–1.91), 0.392 | |||
| High-volume tumor | ||||||
| Yes vs no | 1.66 (0.75–3.67), 0.207 | 2.58 (1.07–6.74), 0.040* | 1.42 (0.34–5.99) | 1.48 (0.41–5.39), 0.551 | ||
| ISUP grade | ||||||
| ≤4 vs 5 | 1.30 (0.62–2.72), 0.495 | 1.49 (0.66–3.35), 0.334 | 0.76 (0.25–2.33), 0.631 | |||
| IDC-P | ||||||
| Positive vs negative | 1.96 (0.93–4.13), 0.078 | 2.48 (1.12–5.51), 0.025* | 0.69 (0.22–2.20), 0.532 | 6.47 (1.37–30.56), 0.018* | 1.11 (0.18–6.87), 0.914 | |
| AKR1C3 | ||||||
| Positive vs negative | 0.55 (0.16–1.86), 0.339 | 0.73 (0.21–2.55), 0.623 | 2.89 (0.65–12.96), 0.166 | |||
| PSA <0.2 ng ml−1 duration (month) | ||||||
| ≥10 vs <10 | 0.06 (0.02–0.15), <0.001* | 0.09 (0.03–0.28), <0.001* | 0.05 (0.02–0.13), <0.001* | 0.08 (0.02–0.35), 0.001* | 0.07 (0.01–0.30), <0.001* | 0.05 (0.003–0.77), 0.031* |
| Rapid and sustained PSA response | ||||||
| Yes vs no | 0.14 (0.06–0.37), <0.001* | 0.30 (0.09–0.98), 0.042* | 0.09 (0.03–0.30), <0.001* | 0.20 (0.04–0.94), 0.040* | 0.19 (0.04–0.85), 0.030* | 0.59 (0.05–6.44), 0.665 |
Rapid and sustained PSA response: achieving PSA <0.2 ng ml−1 within 6 months and maintaining this level for over 10 months. *P < 0.05. PSA: prostate-specific antigen; PSA-PFS: PSA progression-free survival; rPFS: radiographic progression-free survival; OS: overall survival; ALP: alkaline phosphatase; HGB: hemoglobin; LDH: lactate dehydrogenase; ISUP: International Society of Urological Pathology; CI: confidence interval; HR: hazard ratio
DISCUSSION
In recent years, prostate cancer treatment has advanced rapidly, with new drugs approved as first-line therapy for patients with mHSPC, significantly improving survival outcomes. Abiraterone, a first-line therapy for mHSPC, has demonstrated substantial efficacy, leading to a rapid and deep PSA decline in most patients.8 However, some patients do not experience a sustained deep PSA decline, which may indicate a high risk of disease progression. This study investigated the prognostic significance and duration of deep PSA decline in patients with high-risk mHSPC treated with abiraterone. The findings indicated that these patients experienced rapid, deep, and prolonged PSA decline, which was associated with a more favorable prognosis.
Recent studies have shown that a rapid PSA response is a key indicator of treatment efficacy and prognosis in patients undergoing drug therapy.8,12,13 PSA levels serve as a crucial biomarker for monitoring prostate cancer progression, particularly in mHSPC. Patients achieving a PSA level <0.2 ng ml−1 during treatment have been reported to have a 63% lower risk of death.14 Prior studies have also demonstrated that patients with mHSPC who achieve a rapid PSA decline to <0.2 ng ml−1 following endocrine therapy tend to have better survival outcomes.8,17,18 The findings of our study were consistent with these reports, as patients whose PSA dropped below 0.2 ng ml−1 after abiraterone treatment exhibited superior outcomes. Furthermore, post hoc analyses of several large clinical trials have demonstrated that achieving a PSA level <0.2 ng ml−1 within 6–7 months of novel endocrine therapy is significantly associated with improvements in PSA-PFS, rPFS, and OS.8,11,18,19,20,21 Among patients with mHSPC treated with abiraterone, the extent of PSA decline was positively correlated with survival outcomes, with the greatest benefit observed in those achieving a PSA response rate ≥90%.6,22 Beyond survival benefits, mHSPC patients with a rapid PSA decline also exhibited a significantly lower risk of deterioration in the functional assessment of cancer therapy–prostate (FACT-P) score and physical health score, as well as a reduced risk of pain progression and fatigue.13 In our study, patients who demonstrated a rapid PSA response to abiraterone treatment experienced significant benefits in PSA-PFS, rPFS, and OS. These findings align with previous clinical trial data and retrospective studies. Data from clinical trial follow-ups and real-world studies further support the prognostic significance and predictive value of a rapid and deep PSA decline. The PSA response to treatment can also serve as a predictor of drug efficacy, providing valuable guidance for formulating subsequent treatment strategies.
PSA response is an important predictor of drug efficacy, and baseline PSA levels at the time of drug treatment significantly influence prognosis. Nayyar et al.23 demonstrated that higher baseline PSA levels are associated with poorer prognosis. A study by Divrik et al.24 on predictors of response to endocrine therapy in metastatic prostate cancer found that pre-treatment PSA levels predicted both treatment response and prognosis. Additionally, the COU-AA-302 exploratory study showed that abiraterone administration in patients with low PSA levels significantly prolonged survival compared to those with high PSA levels.25 Our study confirmed this finding, suggesting that early initiation of endocrine therapy following a diagnosis of metastatic prostate cancer, particularly in high-risk patients, may lead to a rapid and profound decrease in PSA levels, thereby improving treatment efficacy.
Current clinical trial follow-up analyses and real-world data increasingly highlight the significantly improved prognosis of patients with mHSPC who achieve a rapid and profound PSA decline after treatment with abiraterone and other novel endocrine agents. However, some patients rapidly progress to elevated PSA levels and subsequently develop mCRPC. This suggests that the duration of a rapid and deep PSA decline predicts disease progression. In the cohort with PSA nadir <0.2 ng ml−1, our study found that achieving and maintaining PSA <0.2 ng ml−1 for over 10 months significantly improved clinical outcomes. Further subgroup analysis showed that achieving PSA <0.2 ng ml−1 within 6 months and maintaining this level for over 10 months markedly enhanced patient survival. This finding not only strengthens the prognostic value of PSA response in high-risk patients with mHSPC treated with abiraterone but also provides clearer guidance for medication regimen adjustments.
This study also has a few limitations. As it was conducted at a single medical center, selection bias is unavoidable. And, being a retrospective study, its findings require validation in a larger cohort.
CONCLUSION
This study investigated the predictive value of PSA changes in high-risk patients with mHSPC treated with abiraterone. The findings indicate that patients who experience an early, rapid, and profound PSA decline have a more favorable prognosis. Continuous PSA improvement is an important prognostic indicator, and the speed, depth, and duration of PSA decline are key independent factors influencing prognosis.
AUTHOR CONTRIBUTIONS
QW and MZ performed data collection and analysis and were responsible for study design and the first manuscript draft. QW, MZ, QYZ, Hong Z, and JDD interpreted the results and wrote the final manuscript. SCW, KH, XMZ, and YFS helped formatting the final manuscript. PFS and Hao Z provided methodology consultation and critical revision of this manuscript. All authors read and approved the final manuscript.
COMPETING INTERESTS
All authors declared no competing interests.
The impact of rapid PSA response on prognosis in high-risk mHSPC patients treated with abiraterone. Kaplan–Meier curves of (a) PSA-PFS and (b) rPFS of patients with PSA ≤0.2 ng ml−1 within 6 months and PSA ≤0.2 ng ml−1 exceeding 6 months. PSA: prostate-specific antigen; mHSPC: metastatic hormone-sensitive prostate cancer; PSA-PFS: PSA progression-free survival; rPFS: radiographic progression-free survival; OS: overall survival.
The impact of different PSA nadir durations exceeding 10 months on prognosis in high-risk mHSPC patients treated with abiraterone. Kaplan–Meier curves of (a) PSA-PFS, (b) rPFS, and (c) OS of patients with PSA nadir <0.2 ng ml−1, and PSA nadir ≥0.2 ng ml−1 and <4 ng ml−1. PSA: prostate-specific antigen; mHSPC: metastatic hormone-sensitive prostate cancer; PSA-PFS: PSA progression-free survival; rPFS: radiographic progression-free survival; OS: overall survival.
ACKNOWLEDGMENTS
This work was supported by the Natural Science Foundation of Sichuan Province (No. 2023NSFSC1856, No. 2023NSFSC1858, and No. 2023NSFSC1857) and the Natural Science Foundation of Sichuan Province (No. 23NSFSC2454).
Supplementary Information is linked to the online version of the paper on the Asian Journal of Andrology website.
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Supplementary Materials
The impact of rapid PSA response on prognosis in high-risk mHSPC patients treated with abiraterone. Kaplan–Meier curves of (a) PSA-PFS and (b) rPFS of patients with PSA ≤0.2 ng ml−1 within 6 months and PSA ≤0.2 ng ml−1 exceeding 6 months. PSA: prostate-specific antigen; mHSPC: metastatic hormone-sensitive prostate cancer; PSA-PFS: PSA progression-free survival; rPFS: radiographic progression-free survival; OS: overall survival.
The impact of different PSA nadir durations exceeding 10 months on prognosis in high-risk mHSPC patients treated with abiraterone. Kaplan–Meier curves of (a) PSA-PFS, (b) rPFS, and (c) OS of patients with PSA nadir <0.2 ng ml−1, and PSA nadir ≥0.2 ng ml−1 and <4 ng ml−1. PSA: prostate-specific antigen; mHSPC: metastatic hormone-sensitive prostate cancer; PSA-PFS: PSA progression-free survival; rPFS: radiographic progression-free survival; OS: overall survival.