PSA‐detected prostate cancer and the potential for dedifferentiation—estimating the proportion capable of progression

Abstract

The aims were to determine whether prostate-specific antigen (PSA)-detected prostate cancers progress to higher Gleason score during the preclinical screen-detectable phase, and, if so, to estimate the proportion of tumours with progressive potential. We developed two multi-state Markov chain models to represent the natural history of two tumour populations, one with (Model I) and the other without (Model II) the potential for progression. For each, we derived the transition rates between the states and used these estimates to calculate the expected prevalence of preclinical low and intermediate-to-high Gleason score prostate cancers, using data from the Prostate Testing for Cancer and Treatment (ProtecT) study on 2,310 prostate cancers detected by PSA testing in 71,511 men 50-69 years. We compared the expected prevalence for each tumour population to that of the observed based on ProtecT and the European Randomised Study on Screening for Prostate Cancer (ERSPC)-Rotterdam Centre's first round screening data, the latter allowing independent assessment of the two models. The overall expected proportion of low Gleason score tumours was 0.56 under Model I and 0.81 under Model II, whereas the observed proportion based on either ProtecT or ERSPC-Rotterdam was 0.69. Using the observed prevalence from ERSPCRotterdam, we estimated that 22, 33 and 66% of the tumours in men aged 55-59, 60-64 and 65-69 years, respectively, had the potential for progression in the preclinical phase. PSA-detected prostate cancers are a mixture of progressive and nonprogressive tumours with respect to Gleason score. The former may potentially benefit from screening. Identifying cancers with the potential for progression is important to target screening.

Gleason Grade Progression Is Uncommon

“…The authors observed the proportion of advanced stage decreased with PSA screening, but this seemed to be mainly in cases with Gleason score <7, again confirming the strong association between grade and stage as well as the potential for over-diagnosis. Studies have also attempted to estimate the proportion of tumors where Gleason might progress using statistical modeling(21, 22), finding that dedifferentiation is a likely and common event. However, numerous assumptions are required in these statistical models, and the observed data are also compatible with little or no progression in Gleason grade.…”

Clinicopathological and Prognostic Factors in 106 Prostate Cancer Patients Aged ≤55 Years: A Single-Center Study in China

“…Epidemiological studies show that tumor de-differentiation is the main mechanism of PCa progression. Different conclusions have been made regarding whether PSA screening enables diagnosis at an earlier stage [9–11]. However, these sub-clinical (preclinical stage) tumors [12] can be identified up to an average of 10 years in advance, which may allow early-stage diagnosis [9,10].…”

A genetic risk score to guide age-specific, personalized prostate cancer screening

“…All percentiles reported in this manuscript refer to this population. Annualized incidence rate (h percentile ) curves were calculated for each of various percentiles of the PHS from this population (1,5,20,50,80,95,99) with the median PHS (PHS median ) is taken as baseline: Application of an individualized PHS to screening decisions in the clinic would be facilitated by a readily interpretable translation of the PHS to terms familiar to the patient and physician. Thus, we introduce the "Prostate Cancer-Risk age" or PCaR age.…”