中央區攝護腺癌之進階疾病病程與預後：一項縱貫性研究

陳彥儒、黃逸修、張延驊、郭俊逸、黃志賢、鍾孝仁、林志杰、黃奕燊、魏子鈞、黃子豪、顧明軒、許自翔、蔡承翰、陳人傑、潘競成¹、彭昱璟¹

臺北榮民總醫院 泌尿部、¹病理部

Advanced disease course and prognosis of central zone prostate cancer: A longitudinal study

Yen-Ju Chen, Yi-Hsiu Huang, Yen-Hwa Chang, Junne-Yih Kuo, William J Huang, Hsiao-Jen Chung, Chih-Chieh Lin, I-Shen Huang, Tzu-chun Wei, Tzu-Hao Huang, Ming-Hsuan Ku, Tzu-Hsiang Hsu, Cheng-Han Tsai, Jen-Chieh Chen, Chin-Chen Pan¹, Yu-Ching Peng¹

Department of Urology and Pathology and Laboratory Medicine¹, Taipei Veterans General Hospital, Taipei, Taiwan

Purpose:

The central zone (CZ) of the prostate gland is an anatomically distinct region that accounts for approximately 25% of total prostate mass but is rarely associated with carcinoma. Previous studies have reported that CZ tumors represent only 2.5% to 8% of all prostate cancers, yet they demonstrate significantly more aggressive behavior compared to tumors originating in the peripheral zone (PZ) or transition zone (TZ), including higher rates of extracapsular extension, seminal vesicle invasion, and early biochemical failure.

Cohen et al. first characterized CZ carcinoma in a landmark 2008 study of 2,010 radical prostatectomy cases, identifying CZ tumors as a rare but highly aggressive form of prostate carcinoma with a distinct route of spread via the ejaculatory ducts and seminal vesicles. However, data regarding the disease course and long-term prognosis of CZ prostate cancer remain limited, particularly in Asian populations. To our knowledge, longitudinal studies characterizing the advanced disease course and prognostic outcomes of CZ prostate cancer following radical prostatectomy are scarce.

The purpose of this study was to evaluate the disease course, clinicopathological features, and prognostic outcomes of central zone prostate cancer in a contemporary cohort of patients who underwent radical prostatectomy, with particular attention to pathological staging, Gleason grading patterns, biochemical recurrence (BCR), imaging recurrence (IMGR), and overall survival.

Materials and Methods:

Study Population

This longitudinal study included 97 consecutive patients diagnosed with central zone prostate cancer who underwent radical prostatectomy at our institution between January 2021 and December 2022. All patients had pathologically confirmed CZ involvement on post-surgical whole-mount pathological analysis. The surgical approach was robot-assisted radical prostatectomy (RARP) in 95 patients (97.9%) and retropubic radical prostatectomy (RRP) in 2 patients (2.1%).

Pathological Assessment

Post-surgical pathological reports were reviewed systematically for each patient. Data collected included initial prostate-specific antigen (iPSA), pathological tumor stage according to the TNM classification system, Gleason score with primary and secondary patterns, and International Society of Urological Pathology (ISUP) grade group. Detailed whole-mount sectional zonal mapping was performed to characterize the spatial distribution of tumor foci across the CZ, PZ, TZ, and anterior stroma (AS) at multiple prostatic levels (base, mid-gland, and lower/apical), as well as the presence and location of extracapsular extension (ECE) at each tumor site.

Follow-Up and Outcome Measures

Patients were followed postoperatively with serial PSA measurements. Follow-up data were available for 28 patients (28.9%) with a mean follow-up duration of 39.4 ± 12.4 months (median 45.1 months). The primary outcome measures included biochemical recurrence (BCR), defined as a detectable postoperative serum PSA ≥ 0.2 ng/mL; imaging recurrence (IMGR), defined as evidence of local or distant recurrence on cross-sectional or nuclear medicine imaging; receipt of salvage radiation therapy (RT); and all-cause mortality.

Statistical Analysis

Descriptive statistics were used to summarize patient demographics, clinicopathological features, and outcomes. Continuous variables were reported as mean ± standard deviation and median with range. Categorical variables were reported as frequencies and percentages. Subgroup analyses were performed to evaluate BCR rates stratified by pathological stage and Gleason score pattern.

Results:

Patient Demographics and Clinical Characteristics

A total of 97 patients with central zone prostate cancer were identified, with 48 patients (49.5%) undergoing surgery in 2021 and 49 patients (50.5%) in 2022. The mean age at surgery was 71.3 ± 6.3 years (median 72; range 56–84). The mean preoperative serum iPSA was 22.8 ± 36.3 ng/mL (median 13.7; range 1.1–328.0 ng/mL).

Pathological Staging and Tumor Aggressiveness

The pathological stage distribution demonstrated a striking predominance of advanced disease. Organ-confined disease (T2) was found in only 16 patients (16.5%), while 81 patients (83.5%) had extraprostatic extension (≥T3). Seminal vesicle invasion (T3b) was present in 52 patients (53.6%), and 1 patient (1.0%) had T4 disease with invasion of adjacent structures. Lymph node metastases (N1) were identified in 11 patients (11.3%).

The Gleason score distribution was heavily weighted toward high-grade disease: 99.0% of tumors with evaluable Gleason scores demonstrated Gleason 7 or higher. The most common pattern was Gleason 4+3 = 7 (38.1%), followed by Gleason 4+5 = 9 (20.6%) and Gleason 3+4 = 7 (23.7%). Notably, 36.5% of tumors were Gleason 8 or higher. Correspondingly, ISUP Grade Group 3 was the most prevalent (38.1%), followed by Grade Group 5 (25.8%), Grade Group 2 (23.7%), Grade Group 4 (10.3%), and Grade Group 1 (1.0%). The predominance of Gleason pattern 4 as the primary component (in 74.2% of evaluable cases) underscores the high-grade nature of CZ tumors.

Oncological Outcomes

Among 28 patients with available follow-up data (mean follow-up 39.4 ± 12.4 months; median 45.1 months), biochemical recurrence was observed in 7 patients (25.0%), with a median time to BCR of 12.5 months (range 5.9–37.0 months). The relatively short interval to BCR is consistent with the aggressive nature of CZ prostate cancer.

Imaging recurrence was documented in 4 of 27 evaluable patients (14.8%), occurring at a median of 15.3 months post-surgery (range 7.4–22.2 months). Eight patients (28.6% of the follow-up cohort) received salvage radiation therapy. Three patients (3.1% of the total cohort) died during the study period, at a mean of 39.9 months post-surgery (range 37.0–42.0 months). All 3 deaths occurred in patients with Gleason 9 disease and T3b staging.

Conclusion:

Central zone prostate cancer is associated with advanced pathological staging, high Gleason grades, and an aggressive disease course with early biochemical recurrence. These findings reinforce the importance of recognizing CZ tumor origin in pathological reporting and suggest that patients with CZ prostate cancer may benefit from more intensive postoperative surveillance and potentially earlier adjuvant therapy. Preoperative identification of CZ tumors through targeted biopsy strategies and multiparametric MRI may enable better risk stratification and treatment planning for this high-risk subset of prostate cancer patients.