To identify the risk of failure of active surveillance (AS) in men who had the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria and had undergone radical prostatectomy (RP), by studying as primary endpoints the risk of unfavourable disease in RP specimens (stage >T2 and/or Gleason score >6) and of biochemical progression after RP.
Patients and methods:
We assessed 626 patients who had the PRIAS criteria for AS defined as T1c/T2, PSA level of ≤10 ng/mL, PSA density (PSAD) of <0.2 ng/mL per mL, Gleason score of <7, and one or two positive biopsies. All patients underwent immediate RP at our department between January 1991 and December 2010. Multivariate logistic regression was used to test factors correlated with the risk of unfavourable prostate cancer. The risk of progression was tested using multivariate Cox regression models. Biochemical recurrence-free survival (BFS) was established using the Kaplan-Meier method.
Pathological study of RP specimens showed upstaging (>T2) in 129 patients (20.6%), upgrading (Gleason score >6) in 281 (44.9%) and unfavourable disease in 312 patients (50%). There was a statistically non-significant trend for BFS at P = 0.06. Predictors of favourable tumours were age <65 years (P = 0.005), one vs two positive biopsies (P = 0.01) and a biopsy core number >12 (P = 0.005). Preoperative factors predicting disease progression were a PSAD of >0.15 ng/mL(2) (P = 0.008) and biopsy core number of ≤12 (P = 0.017).
Even with stringent AS criteria, the rate of unfavourable disease remains high. Predictive factors of unfavourable disease and biochemical progression should be considered when including patients in AS protocols.
"Similarly, a recent European multicenter study on 919 patients, who fulfilled relatively more stringent selection criteria for AS (PSA, ≤10 ng/mL; clinical stage, T1c; GS, <7; and a single positive core with tumor length, <3 mm), found GS upgrading in 34% and only 26% of patients with pathologically insignificant cancer . Finally, among 626 patients enrolled in Prostate Cancer Research International: Active Surveillance (PRIAS) study who underwent immediate RP, GS upgrading was present in 44.9% . Although the selection criteria for AS differ by institutions, this collective data clearly demonstrates that a single session of TRUS–guided biopsy offers limited accuracy in revealing tumor aggressiveness in potential candidates for AS. "
[Show abstract][Hide abstract] ABSTRACT: To investigate actual intraprostatic location of higher graded tumor foci undetected via standard transrectal ultrasound-guided prostate biopsy amongst patients who would be clinically considered appropriate candidates for active surveillance (AS) but underwent radical prostatectomy (RP).
We reviewed entirely-submitted and whole-mounted RP specimens from 169 men who were deemed appropriate for AS clinically, but opted for RP and were found to have higher grade tumors. For each case, tumor nodules were circled and color-coded in a grade-specific manner and digitally scanned to created tumor maps. The locations of tumor foci with Gleason grade ≥4 were stratified by specific sites: anterior, anterolateral, lateral only (not clearly anterior or posterior), posterior, and posterolateral area.
Of 169 patients, 86% had clinical stage T1c and 14% T2a. RP Gleason score 7 in all but two men. Higher-grade tumor foci were localized to: anterior (n=66, 39%), anterolateral (n=4, 2%), lateral only (not clearly anterior or posterior) (n=5, 3%), posterior (n=52, 31%), and posterolateral (n=42, 25%) prostate, respectively.
Among patients deemed clinically appropriate for AS, higher-grade tumor foci missed by standard prostate biopsies were localized to both the anterior and posterior prostate, without predominance of a particular area. These findings lend additional support to performing repeat standard prostate biopsy in potential candidates for AS and should be considered in efforts to optimize current biopsy strategies for the selection of AS patients.
"On a group level it is reasonable to manage all men with low-risk prostate cancer conservatively. However , some men with prostate cancer categorized as low risk harbour more aggressive cancer, which is not detected by the diagnostic biopsies    . The clinical challenge for urologists is to identify men with such cancers, as they can benefit from curative therapy, while sparing men with genuinely low-risk prostate cancer the side-effects of curative treatment. "
[Show abstract][Hide abstract] ABSTRACT: Objective
Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods.
Material and methods
SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10–15 years.
Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres.
It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule.
[Show abstract][Hide abstract] ABSTRACT: Genetic risk factors are important contributors to the development of colorectal cancer. Following the definition of a linkage signal at 9q22-31, we fine mapped this region in an independent collection of colon cancer families. We used a custom array of single-nucleotide polymorphisms (SNP) densely spaced across the candidate region, performing both single-SNP and moving-window association analyses to identify a colon neoplasia risk haplotype. Through this approach, we isolated the association effect to a five-SNP haplotype centered at 98.15 Mb on chromosome 9q. This haplotype is in strong linkage disequilibrium with the haplotype block containing HABP4 and may be a surrogate for the effect of this CD30 Ki-1 antigen. It is also in close proximity to GALNT12, also recently shown to be altered in colon tumors. We used a predictive modeling algorithm to show the contribution of this risk haplotype and surrounding candidate genes in distinguishing between colon cancer cases and healthy controls. The ability to replicate this finding, the strength of the haplotype association (odds ratio, 3.68), and the accuracy of our prediction model (approximately 60%) all strongly support the presence of a locus for familial colon cancer on chromosome 9q.
Cancer Research 07/2010; 70(13):5409-18. DOI:10.1158/0008-5472.CAN-10-0188 · 9.33 Impact Factor
David M Erekson, Michael J Lambert, Dennis L Eggett
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