The presence of primary circulating prostate cells is associated with upgrading and upstaging in patients eligible for active surveillance.

Nigel P Murray,Sócrates Aedo,Eduardo Reyes,Omar Jacob,Cynthia Fuentealba

doi:10.3332/ecancer.2017.711

Nigel P Murray, Sócrates Aedo + Show 3 more

Open Access

https://doi.org/10.3332/ecancer.2017.711

Copy DOI

Abstract

Active surveillance (AS) is a considered treatment option for men with low or very low-risk prostate cancer. However, on repeat biopsy some 25% were upgraded and recommended for active treatment. We compare the presence or absence of primary circulating prostate cells (CPCs) with the clinical pathological findings after radical prostatectomy in men fulfilling the criteria for active surveillance and the risk of reclassification for active observation (AO).Methods and patientsA single centre observational study was done involving 102 men who fulfilled the Epstein criteria for AS and underwent radical prostatectomy as mono-therapy for prostate cancer. The patients were classified according to the presence or absence of CPCs detected immediately before the prostate biopsy. Mononuclear cells were obtained by differential gel centrifugation of 8 mL of venous blood and CPCs identified using immunocytochemistry with anti-PSA and anti-P504S. A positive CPC test was defined as at least 1 PSA (+), P504S (+) cell detected/blood sample. The surgical specimen was analysed for Gleason score and pathological stage.ResultsA total of 25 out of 102 (24.5%) men were upgraded based on the pathological findings of the surgical specimen. Among which 45 (44%) men were positive for CPCs. They were younger, 63.9 versus 68.1 years (p = 0.0148), had a lower frequency of pT2 or lower disease (64.4% versus 91.2% p <0.001), higher median Gleason scores (6 versus 5 p < 0.001) in both the biopsy and surgical specimens, and a higher frequency of upgrading 44% versus 9% (p < 0.001)ConclusionsIn men fulfilling the criteria for AS, the presence of primary CPCs suggests a high risk for disease upgrade and therefore these men may not be ideal for observational therapy. Further studies with a larger population are warranted.

Highlights

Active surveillance (AS) is a recognised initial treatment option for men with early stage low-grade prostate cancer
In men fulfilling the criteria for AS, the presence of primary circulating prostate cells (CPCs) suggests a high risk for disease upgrade and these men may not be ideal for observational therapy
According to the Prostate Cancer Intervention Versus Observation Trial (PIVOT) [3], men with low risk disease defined as a prostate specific antigen (PSA) ≤ 10ng/mL, a Gleason score ≤ 6, and T stage 1 or 2a had no difference in mortality, i.e., in terms of all-cause mortality and prostate cancer specific mortality

Summary

Introduction

Active surveillance (AS) is a recognised initial treatment option for men with early stage low-grade prostate cancer. Using these criteria to select patients with 'insignificant disease' has a positive predictive value of 95% and a negative predictive value of 66% [5] These men are actively followed up with repeat annual biopsies; the timing of intervention after the initial diagnosis is based on variables such as PSA kinetics, Gleason grade progression, patient preference and/or clinical or radiologic evidence of disease progression [1, 6]. A similar increase is seen in men subjected to immediate repeat biopsy when entering an AO programme [9] This short time interval in comparison with the long natural history of prostate cancer suggests that sampling error rather than tumour progression is probably the primary source of tumour upgrading in these men. The use of other biomarkers, such as CPCs, could be useful in re-defining these patients who could be more adequately treated by AS

Methods

Results

Discussion

Conclusion