Abstract Background Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing ...interest as an alternative to radical treatment of low-risk PCa. Objective To update our experience in the largest worldwide prospective AS cohort. Design, setting, and participants Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤6. PSA was measured every 3–6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification. Outcome measurements and statistical analysis Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy–free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time. Results and limitations In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS. Conclusions Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized. Trial registration The current program is registered at the Dutch Trial Register with ID NTR1718 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718 ).
Objective
To study the risk of serial prostate biopsies on complications in men on active surveillance (AS) and determine the effect of complications on receiving further biopsies.
Patients and ...methods
In the global Prostate cancer Research International: Active Surveillance (PRIAS) study, men are prospectively followed on AS and repeat prostate biopsies are scheduled at 1, 4, and 7 years after the diagnostic biopsy, or once yearly if prostate‐specific antigen‐doubling time is <10 years. Data on complications after biopsy, including infection, haematuria, haematospermia, and pain, were retrospectively collected for all biopsies taken during follow‐up in men from several large participating centres. Generalised estimating equations were used to test predictors of infection after biopsy. Competing risk analysis was used to compare the rates of men receiving further biopsies between men with and without previous complications.
Results
In all, 2 184 biopsies were taken in 1 164 men. Infection was reported after 55 biopsies (2.5%), and one in five men reported any form of complication. At multivariable analysis, the number of previous biopsies was not a significant predictor of infection (odds ratio 1.04, 95% confidence interval 0.76–1.43). The only significant predictor for infection was the type of prophylaxis used. Of all men with a complication at the diagnostic or first repeat biopsy, 21% did not have a repeat biopsy at the time a repeat biopsy was scheduled according to protocol, vs 12% for men without a previous biopsy complication.
Conclusion
In our present cohort of men on AS, we found no evidence that repeat prostate biopsy in itself posed a risk of infection. However, complications after biopsy were not uncommon and after a complication men were less likely to have further biopsies. We should aim to safely reduce the amount of repeat biopsies in men on AS.
Metachromatic leukodystrophy (MLD) is a lysosomal enzyme deficiency disorder leading to progressive demyelination and, consecutively, to cognitive and motor decline. Brain magnetic resonance imaging ...(MRI) can detect affected white matter as T2 hyperintense areas but cannot quantify the gradual microstructural process of demyelination more accurately. Our study aimed to investigate the value of routine MR diffusion tensor imaging in assessing disease progression.
MR diffusion parameters (apparent diffusion coefficient ADC and fractional anisotropy FA) were in the frontal white matter, central region (CR), and posterior limb of the internal capsule in 111 MR datasets from a natural history study of 83 patients (age: 0.5-39.9 years; 35 late-infantile, 45 juvenile, 3 adult, with clinical diffusion sequences of different scanner manufacturers) as well as 120 controls. Results were correlated with clinical parameters reflecting motor and cognitive function.
ADC values increase and FA values decrease depending on disease stage/severity. They show region-specific correlations with clinical parameters of motor and cognitive symptoms, respectively. Higher ADC levels in CR at diagnosis predicted a disease course with more rapid motor deterioration in juvenile MLD patients. In highly organized tissues such as the corticospinal tract, in particular, diffusion MR parameters were highly sensitive to MLD-associated changes and did not correlate with the visual quantification of T2 hyperintensities.
Our results show that diffusion MRI can deliver valuable, robust, clinically meaningful, and easily obtainable/accessible/available parameters in the assessment of prognosis and progression of MLD. Therefore, it provides additional quantifiable information to established methods such as T2 hyperintensity.
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