BERKELEY, CA (UroToday.com) - Active surveillance (AS) for low-risk prostate cancer (PC) aims to prevent, or at least delay, invasive therapy and its potential side effects in carefully selected men, mainly those with screen-detected disease.
Repeat biopsies at predefined time intervals are a common part of AS protocols, and are intended to detect men who are considered to have unfavourable disease and should be offered radical therapy, despite seemingly low-risk features at diagnosis.
Prostate Cancer Research International: Active Surveillance (PRIAS) is a prospective, observational study, which originated from the European Randomized Study of Screening for Prostate Cancer (ERSPC). It provides a protocol for the inclusion and follow-up of low-risk PC patients that is being used by urologists worldwide via a web-based instrument (www.prias-project.org). This protocol schedules a first repeat biopsy one year after diagnosis to evaluate potential reclassification of the tumour to higher risk disease. In order to contribute to risk stratification for men on AS, we studied the outcomes of repeat biopsies and predictive factors for risk reclassification to more aggressive disease.
Patients who were eligible met all of the inclusion criteria for low-risk PC (clinical stage ≤T2, PSA ≤10 ng/ml, prostate-specific antigen density [PSA-D] <0.2 ng/ml/ml, 1 or 2 positive biopsy cores, and Gleason score [GS] ≤6). PSA was measured 3-monthly and the first, volume-dependent repeat biopsy was scheduled 1 year after diagnosis, independent of PSA doubling time (PSA-DT). Risk reclassification into high-risk on repeat biopsy was defined as ≥3 positive biopsy cores or GS ≥7. Multivariate logistic regression analysis was performed to evaluate the association of all baseline characteristics and PSA-DT with risk reclassification towards high-risk on repeat biopsy.
A first repeat biopsy was taken in 757 patients after median follow-up of 1.03 yrs. The results of repeat biopsies were favourable (no or low-risk PC) in 594 patients (78.5%) and led to reclassification of risk in 163 (21.5%). Analysis showed that reclassification to higher risk was significantly influenced by the number of initial positive cores (2 vs. 1) (OR =1.8; p =0.002) and higher PSA density (OR =2.1; p =0.003). Age, clinical stage, total number of biopsy cores, or PSA did not significantly influence the outcome. Adding PSA-DT at time of repeat biopsy to the model showed PSA-DT <3 yrs="" to="" be="" significantly="" associated="" with="" reclassification="" higher="" risk="" or="1.7;" p="0.015).</p">
Current results show a higher risk of reclassification to more aggressive disease on repeat biopsy in 21.5% of men after a median follow-up of 1 year within a protocol-based AS setting. It was demonstrated that a higher PSA-D and having 2 positive biopsy cores instead of 1 at diagnosis are significant, independent predictors of adverse histological features on repeat biopsy. Furthermore, a short PSA-DT at the time of repeat biopsy is also associated with adverse characteristics.
The rationale for AS is to select men with low-risk disease by means of favourable characteristics at diagnosis to subsequently prevent or delay invasive treatment with its possible side-effects. At least a quarter of patients with screen-detected PC (prevalence screen) are eligible for AS according to PRIAS criteria. However, some patients who are apparently at favourable risk, harbour more aggressive disease, which therefore justifies intensive monitoring to offer deferred treatment in a still curable stage if necessary. Reclassification of risk is not a rare phenomenon and repeat biopsies are an important part of follow-up protocols in AS to check for correct classification of disease and monitor for potential reclassification over time. Although postponing a repeat biopsy until after 1 year is not likely to cause progression of disease beyond curability, it seems advisable to offer repeat biopsy in an early stage to confirm eligibility, especially in men with a combination of characteristics predicting increased chance of risk reclassification. Our protocol recommends performing volume-based biopsies to reduce sampling errors and provide good risk assessment.
Clinical features at baseline and during follow-up in men with apparently low-risk PC can be used to significantly predict short-term unfavourable repeat biopsy results. These variables can potentially be used for better selection and risk stratification of men on AS programs to either reassure them or subject them to early repeat biopsy and curative intervention if necessary. Longer follow-up results from AS studies are essential for further improvement of criteria for inclusion and follow-up.
Meelan Bul,*, Roderick C.N. van den Bergh,a Antti Rannikko,b Riccardo Valdagni,c Tom Pickles,d Chris H. Bangma,a and Monique J. Roobola as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
- Department of Urology, Erasmus MC, Rotterdam, the Netherlands
- Department of Urology, Helsinki University Central Hospital, Helsinki, Finland
- Prostate program, Scientific Directorate, Fondazione IRCSS Instituto Nazionale dei Tumori, Milan, Italy
- Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver, Canada