We assessed whether an association exists between a change in prostate specific antigen and biopsy progression in men on active surveillance.
A cohort of patients undergoing active surveillance for prostate cancer was identified from the urological oncology database at our institution. Multivariate logistic regression was performed to determine whether prostate specific antigen velocity, defined as the change in ln(prostate specific antigen) per year, is associated with biopsy progression, defined as a Gleason upgrade or volume progression on repeat biopsy within 24 months of diagnosis.
A total of 241 men with a mean ± SD age of 61 ± 7 years and mean prostate specific antigen 4.9 ± 2.2 ng/ml met study inclusion criteria. Median time to repeat biopsy was 10 months (IQR 6-13). Biopsy progression developed in 55 men (23%), including a Gleason score upgrade in 46 (19%), greater than 33% positive cores in 11 (5%) and greater than 50% maximum single core positive in 12 (5%). The median prostate specific antigen ratio per year was 1.0 (IQR 0.95-1.03), although 1 man had a ratio of greater than 1.26 (doubled over 3 years) and 7 had a ratio of less than 1/1.26 (halved over 3 years). On multivariate analysis prostate specific antigen doubling within 3 years was associated with a 1.4-fold increase in the odds of biopsy progression (OR 1.4, 95% CI 0.6-3.4, p = 0.46).
There is little change in prostate specific antigen during the first 24 months of surveillance in men with well staged, low risk prostate cancer. We believe that these findings highlight the importance of repeat biopsy during surveillance.
"We then excluded 19 men for whom the period from biopsy to surgery was over 6 months and 33 men who received neoadjuvant hormone therapy. Of the remaining 1434 patients, we identified 577 men (group A) who met at least one of AS selection criteria used by the following institutions: Johns Hopkins Medical Institution (Hopkins) , Memorial Sloan-Kettering Cancer Center (MSKCC) , Prostate Cancer Research International: Active Surveillance (PRIAS) , University of Miami (Miami) , University of California, San Francisco (UCSF) , and University of Toronto (Toronto) . The criteria implemented by each institution are summarized in Table 1. "
[Show abstract][Hide abstract] ABSTRACT: Introduction
We analyzed whether expansion of existing active surveillance (AS) protocols to include men with biopsy Gleason score (GS) 3+4 prostate cancer (PCa) would significantly alter pathologic and biochemical outcomes of potential candidates of AS.
Among patients who underwent radical prostatectomy at our center between 2006 and 2013, we identified 577 patients (group A) who preoperatively fulfilled at least one of 6 different AS criteria. Also, we identified 217 patients (group B) with biopsy GS 3+4 but fulfilled non-GS criteria from at least one of 6 AS criteria. Designating group C as expanded group incorporating all patients in group A and B, we compared risk of unfavorable disease (pathologic GS ≥4+3 and/or pathologic T stage ≥pT3a) and biochemical recurrence (BCR)-free survival between groups.
Rates of unfavorable disease were not significantly different between patients of group A and C who met AS criteria from 5 institutions (all p>0.05), not including University of Toronto (p<0.001). Also BCR-free survivals were not significantly different between patients in group A and C meeting each of 6 AS criteria (all p>0.05). Among group B, PSAD>0.15 ng/mL/cm3 (p = 0.011) and tumor length of biopsy GS 3+4 core>4 mm (p = 0.007) were significant predictors of unfavorable disease. When these two criteria were newly applied in defining group B, rates of unfavorable disease in group A and B was 15.6% and 14.7%, respectively (p = 0.886).
Overall rate of pathologically aggressive PCa harbored by potential candidates for AS may not be increased significantly with expansion of criteria to biopsy GS 3+4 under most contemporary AS protocols. PSAD and tumor length of biopsy GS 3+4 core may be useful predictors of more aggressive disease among potential candidates for AS with biopsy GS 3+4.
PLoS ONE 09/2014; 9(9):e109031. DOI:10.1371/journal.pone.0109031 · 3.23 Impact Factor
"However, the PSA values over time that can predict disease progression during AS remain unknown . Klotz et al. , the Johns Hopkins group , and the University of California San Francisco cohort  focused on PSA kinetics to determine the triggers indicating that AS should be discontinued. However, no correlations were found between the PSA DT and adverse pathologic findings from the surveillance biopsy. "
[Show abstract][Hide abstract] ABSTRACT: This study was conducted to describe our early experience with active surveillance (AS).
Between January 2008 and December 2012, 35 patients were treated with AS. Selection criteria included the following: Gleason score ≤6 with single positive core, clinical stage ≤T1c, prostate-specific antigen (PSA) ≤10 ng/mL, and unremarkable imaging results. On patient follow-up, we regularly measured PSA (every 3-6 months) and performed prostate biopsies (after 1 and 3 years).
In the first year of follow-up, prostate biopsies were performed in 25 patients (13 patients, negative for cancer; 7 patients, Gleason score of 6 without progression; 5 patients, progression, treated with radical prostatectomy [RP]). In the third year of follow-up, prostate biopsies were performed in five patients (two patients, negative for cancer; one patient, Gleason score of 6 without progression; two patients, progression, treated with RP). Seven patients discontinued AS because of increased anxiety, and three patients were lost to follow-up. Overall, seven patients (28%) who experienced progression had a mean PSA doubling time (DT) of 7.54 years. Six patients had a PSA DT of more than 3 years, whereas one had a PSA DT of less than 3 years. This study was limited by its small sample size and short follow-up period.
PSA kinetics did not correlate with progression, which suggests that regular biopsies should still be performed. AS is an available treatment option for patients with a low risk of prostate cancer but should only be used in carefully selected patients.
Korean journal of urology 03/2014; 55(3):167-71. DOI:10.4111/kju.2014.55.3.167
"mortality (≤3%) of these AS series makes surveillance very appealing in men with low-risk disease, but most of these data represent relatively short-term follow-up given the long natural history of low-grade prostate cancer. Additionally, monitoring protocols vary substantially between institutions and triggers for intervention have yet to be standardized [55,56]. "
[Show abstract][Hide abstract] ABSTRACT: Today, the majority of men with newly diagnosed prostate cancer will present with low-risk features of the disease. Because prostate cancer often takes an insidious course, it is debated whether the majority of these men require radical treatment and the accompanying derangement of quality of life domains imposed by surgery, radiation, and hormonal therapy. Investigators have identified various selection criteria for "insignificant disease," or that which can be monitored for disease progression while safely delaying radical treatment. In addition to the ideal definition of low risk, a lack of randomized trials comparing the various options for treatment in this group of men poses a great challenge for urologists. Early outcomes from active surveillance cohorts support its use in carefully selected men with low-risk disease features, but frequent monitoring is required. Patient selection and disease monitoring methods will require refinement that will likely be accomplished through the increased use of biomarkers and specialized imaging techniques.
Korean journal of urology 07/2013; 54(7):417-25. DOI:10.4111/kju.2013.54.7.417
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