Urological Cancers of Men
Reporter and Curator: Larry H. Bernstein, MD, FCAP
Impact of the U.S. Preventive Services Task Force Recommendations Against PSA Screening on Prostate Biopsy and Cancer Detection Rates.
B Bhindi, M Mamdani, GS Kulkarni, A Finelli, RJ Hamilton, J Trachtenberg, et al.
The Journal of Urology 12/2014; http://dx.doi.org:/10.1016/j.juro.2014.11.096
To determine if the USPSTF recommendation against PSA screening was associated with a change in biopsy and cancer detection rates.
We conducted a time series analysis (10/2008-06/2013) of prostate biopsies performed at University Health Network (Toronto). Biopsies for active surveillance or solely targeting MRI-detected lesions were excluded. Interventional auto-regressive integrated moving average (ARIMA) models with step functions were used to examine changes in the number of biopsies performed and cancers detected per month. Low risk PC (LRPC) was defined as no Gleason pattern ≥4, ≤3 cores involved or ≤1/3 of total number of cores involved, and no core with >50% cancer involvement. Intermediate-to-high grade PC (I-HGPC) was defined as Gleason 7-10.
A total of 3408 biopsies were performed and 1601 (47.0%) PCs were detected (LRPC=563 (16.5%); I-HGPC=914 (26.8%)). The median number of biopsies per month decreased from 58.0 (IQR=54.5-63.0) before recommendations to 35.5 (IQR=27.0-41.0) afterward (p=0.003), while median number of patients undergoing their first-time biopsies decreased from 42.5 (IQR=37.5-45.5) to 24.0 (IQR=19.0-32.5, p=0.025). The median number of LRPCs detected per month decreased from 8.5 (IQR=6.5-10.5) to 5.5 (IQR=4.0-7.0, p=0.012), while the median number of I-HGPCs per month decreased from 17.5 (IQR=14.5-21.5) to 10.0 (IQR=9.0-12.0, p<0.001).
Following the USPSTF recommendation, the number of biopsies performed (total and first-time biopsies), based on referrals from our catchment area, have decreased. This is likely due to decreased use of PSA-screening. Although encouraging that fewer low risk PCs are being diagnosed, the sudden decrease in the detection rate of Gleason 7-10 PCs is concerning.
Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study.
E Lalonde, AS Ishkanian, J Sykes, M Fraser, H Ross-Adams, N Erho, et al.
The Lancet Oncology 12/2014; 15(13):1521-32.
http://dx.doi.org:/10.1016/S1470-2045(14)71021-6
Clinical prognostic groupings for localised prostate cancers are imprecise, with 30-50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors.
We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy. We validated these indices in two independent cohorts of 154 (Memorial Sloan Kettering Cancer Center cohort [MSKCC] cohort) and 117 (Cambridge cohort) radical prostatectomy specimens from low-risk to high-risk patients. We applied unsupervised and supervised machine learning techniques to the copy-number profiles of 126 pre-image-guided radiotherapy diagnostic biopsies to develop prognostic signatures. Our primary endpoint was the development of a set of prognostic measures capable of stratifying patients for risk of biochemical relapse 5 years after primary treatment.
Biochemical relapse was associated with indices of tumour hypoxia, genomic instability, and genomic subtypes based on multivariate analyses. We identified four genomic subtypes for prostate cancer, which had different 5-year biochemical relapse-free survival. Genomic instability is prognostic for relapse in both image-guided radiotherapy (multivariate analysis hazard ratio [HR] 4·5 [95% CI 2·1-9·8]; p=0·00013; area under the receiver operator curve [AUC] 0·70 [95% CI 0·65-0·76]) and radical prostatectomy (4·0 [1·6-9·7]; p=0·0024; AUC 0·57 [0·52-0·61]) patients with prostate cancer, and its effect is magnified by intratumoral hypoxia (3·8 [1·2-12]; p=0·019; AUC 0·67 [0·61-0·73]). A novel 100-loci DNA signature accurately classified treatment outcome in the MSKCC low-risk to intermediate-risk cohort (multivariate analysis HR 6·1 [95% CI 2·0-19]; p=0·0015; AUC 0·74 [95% CI 0·65-0·83]). In the independent MSKCC and Cambridge cohorts, this signature identified low-risk to high-risk patients who were most likely to fail treatment within 18 months (combined cohorts multivariate analysis HR 2·9 [95% CI 1·4-6·0]; p=0·0039; AUC 0·68 [95% CI 0·63-0·73]), and was better at predicting biochemical relapse than 23 previously published RNA signatures.
This is the first study of cancer outcome to integrate DNA-based and microenvironment-based failure indices to predict patient outcome. Patients exhibiting these aggressive features after biopsy should be entered into treatment intensification trials.
Prostate cancer: Is prostatectomy for Gleason score 6 a treatment failure?
Theodorus H van der Kwast, Monique J Roobol
Nature Reviews Urology 12/2014; http://dx.doi.org:/10.1038/nrurol.2014.335
Molecular and clinical support for a four-tiered grading system for bladder cancer based on the WHO 1973 and 2004 classifications
BWG van Rhijn, M Musquera, L Liu, AN Vis, TCM Zuiverloon, GJLH van Leenders, WJ Kirkels, EC Zwarthoff, ER Boevé, …, TH van der Kwast
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 11/2014; http://dx.doi.org:/10.1038/modpathol.2014.154
Currently, the use of two classification systems for bladder cancer grade is advocated in clinical guidelines because the WHO2004 classification has not been sufficiently validated with biological markers and follow-up. The slides of 325 primary non-muscle invasive bladder cancers from three hospitals were reviewed by one uro-pathologist in two separate sessions for the WHO1973 (G1, G2 and G3) and 2004 (papillary urothelial neoplasm of low malignant potential (LMP), low-grade (LG) and high-grade (HG)) classifications. FGFR3 status was examined with PCR-SNaPshot analysis. Expression of Ki-67, P53 and P27 was analyzed by immuno-histochemistry. Clinical recurrence and progression were determined. We performed validation and cross-validation of the two systems for grade with molecular markers and clinical outcome. Multivariable analyses were done to predict prognosis and pT1 bladder cancer. Grade review resulted in 88 G1, 149 G2 and 88 G3 lesions (WHO1973) and 79 LMP, 101 LG and 145 HG lesions (WHO2004). Molecular validation of both grading systems showed that FGFR3 mutations were associated with lower grades whereas altered expression (Ki-67, P53 and P27) was found in higher grades. Clinical validation showed that the two classification systems were both significant predictors for progression but not for recurrence. Cross-validation of both WHO systems showed a significant stepwise increase in biological (molecular markers) and clinical (progression) potential along the line: G1-LG-G2-HG-G3. The LMP and G1 categories had a similar clinical and molecular profile. On the basis of molecular biology and multivariable clinical data, our results support a four-tiered grading system using the 1973 and 2004 WHO classifications with one low-grade (LMP/LG/G1) category that includes LMP, two intermediate grade (LG/G2 and HG/G2) categories and one high-grade (HG/G3) category.Modern Pathology advance online publication, 28 November 2014; doi:10.1038/modpathol.2014.154.
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