Impact of stage migration and practice changes on high-risk prostate cancer: results from patients treated with radical prostatectomy over the last two decades

Abstract

Objective: To evaluate the impact of year of surgery on clinical, pathological and oncological outcomes of patients with high-risk prostate cancer.

Patients and methods: We evaluated 1 033 patients with clinically high-risk prostate cancer, defined as the presence of at least one of the following risk factors: preoperative prostate-specific antigen (PSA) level >20 ng/mL, and/or clinical stage ≥T3, and/or biopsy Gleason score ≥8. Patients were treated between 1990 and 2013 at a single institution. The year-by-year trends in clinical and pathological characteristics were examined. Multivariable Cox regression analysis was used to test the relationship between year of surgery and oncological outcomes.

Results: We observed a decrease over time in the proportion of patients with high-risk disease (preoperative PSA >20 ng/mL or clinical stage cT3). A trend in the opposite direction was seen for biopsy Gleason score ≥8 tumours. We observed a considerable increase in the median number of lymph nodes removed, which was associated with an increased rate of lymph node invasion (LNI). On multivariable Cox regression analysis, year of surgery was associated with a reduced risk of biochemical recurrence (hazard ratio [HR] per 5-year interval 0.90, 95% confidence interval [CI] 0.84-0.96; P = 0.01) and distant metastasis (HR per 5-year interval 0.91, 95% CI 0.83-0.99; P = 0.039), after adjusting for age, preoperative PSA, pathological stage, LNI, surgical margin status, and pathological Gleason score.

Conclusions: In this single-centre study, an increased diagnosis of localized and less extensive high-grade prostate cancer was observed over the last two decades. Patients with high-risk disease who were selected for radical prostatectomy showed better cancer control over time. Better definitions of what constitutes high-risk prostate cancer among contemporary patients are needed.

Keywords: cancer recurrence; high risk; prostate cancer; radical prostatectomy; stage migration.

Figure 1

Changes of clinical characteristics over the study period. Figures represent the proportion of patients diagnosed with PSA >20ng/ml (Figure 1A), clinical stage cT3 (Figure 1B) and biopsy Gleason score ≥8 (Figure 1C). Figure 1D represents the proportion of patients classified according to the number of high-risk factors at diagnosis. Green solid line: 1 high-risk factor. Orange dashed line: 2 high-risk factors. Red dotted line: 3 high-risk factors. Shaded area: 95% confidence interval.

Figure 2

Changes of pathologic characteristics over the study period. Figure 2A: pathologic stage ≥pT3b. Figure 2B: pathologic Gleason score ≥8. Figure 2C: positive surgical margins. Figure 2D: lymph node invasion. Figure 2E: number of total (blue line) and positive (red line) lymph nodes removed. Figure 2F: specimen confined disease. Shaded area: 95% confidence interval.

Figure 3

Adjuvant treatments administration over the study period. Blue solid line: adjuvant radiation therapy. Red dashed line: adjuvant hormonal therapy. Dotted lines: 95% confidence interval.

Figure 4

Year – per – year trend analysis of oncologic outcomes over the study period. Blue solid line: Biochemical recurrence rate at 3 years after surgery. Red dashed line: Distant metastasis rate at 5 years after surgery. Green dotted line: Cancer specific mortality rate at 10 years after surgery.