including the need for numerous repeat surveillance biopsies. In this issue of the BJUI, Gallagher et al. [1] report the outcomes of an AS programme using selective repeat biopsy based on multiparametric MRI (mpMRI) and PSA dynamics. The authors address the important issue of whether mpMRI can be used to safely avoid repeat biopsies in AS protocols.The evidence for repeat biopsies in AS is based on studies from the pre-MRI era, where up to 30% of men were upgraded on repeat systematic TRUS biopsy [2]. It has been established that TRUS biopsy is a highly unreliable test and misses a substantial proportion of clinically significant disease. The current approach requiring the repeated application of an unreliable test will not improve the systematic error inherent to the test. It is clear that the pathway needs to be updated for the mpMRI era, and the cohort of men in Gallagher et al.[1] provides valuable reallife clinical data of an mpMRI-based AS programme with a unique 4-year follow-up period.The results are encouraging, with upgrading occurring in only 1.8% of men with a prior negative MRI. With follow-up, progression to radical treatment was 12.8%, which is consistent with the established diagnostic performance of mpMRI. The authors seek further improvements by investigating if PSA dynamics can identify men with a negative MRI at risk of progression. They find that PSA velocity is strongly associated with subsequent progression (AUC 0.95, P < 0.001) and conclude that men on AS with low-risk disease can safely avoid biopsy in favour of MRI, PSA monitoring and selective re-biopsy.This study [1] supports a growing body of evidence that mpMRI may be adopted as the primary surveillance tool for men on AS. The finding regarding PSA velocity should be interpreted carefully as it contrasts with previous studies, which found that PSA dynamics have a limited role as independent predictors of disease progressions in AS [3]. A non-invasive alternative to biopsy would be a valuable addition to AS and improve its acceptability as a management option. The burden of repeat surveillance biopsies for men on AS should not be underestimated. Indeed, in the present study~30% of men declined biopsy in favour of continued mpMRI surveillance.The question is can we adapt our current standard AS approach for the mpMRI era? There are still many challenges and many unanswered questions. The cost-effectiveness of mpMRI surveillance programmes needs to be established and the lack of MRI capacity remains a significant obstacle in introducing mpMRI pathways. The optimal imaging interval and the natural history of mpMRI lesions are just a few of the questions that need further research. These are exciting times to be a researcher in this field and there is much work to do as we start to build the new evidence-base covering all the questions required for the mpMRI era. References 1 Gallagher KM, Christopher E, Cameron AJ et al. Four-year outcomes from a multiparametric magnetic resonance imaging (MRI)-based active surveillance programme: PSA d...
This review presents the current state of the art regarding multiparametric magnetic resonance (MR) imaging of prostate cancer. Technical requirements and clinical indications for the use of multiparametric MR imaging in detection, localization, characterization, staging, biopsy guidance, and active surveillance of prostate cancer are discussed. Although reported accuracies of the separate and combined multiparametric MR imaging techniques vary for diverse clinical prostate cancer indications, multiparametric MR imaging of the prostate has shown promising results and may be of additional value in prostate cancer localization and local staging. Consensus on which technical approaches (field strengths, sequences, use of an endorectal coil) and combination of multiparametric MR imaging techniques should be used for specific clinical indications remains a challenge. Because guidelines are currently lacking, suggestions for a general minimal protocol for multiparametric MR imaging of the prostate based on the literature and the authors' experience are presented. Computer programs that allow evaluation of the various components of a multiparametric MR imaging examination in one view should be developed. In this way, an integrated interpretation of anatomic and functional MR imaging techniques in a multiparametric MR imaging examination is possible. Education and experience of specialist radiologists are essential for correct interpretation of multiparametric prostate MR imaging findings. Supportive techniques, such as computer-aided diagnosis are needed to obtain a fast, cost-effective, easy, and more reproducible prostate cancer diagnosis out of more and more complex multiparametric MR imaging data.
To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10−17), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10−20). rs78378222 is in the 3′ untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3′-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10−6), glioma (OR = 2.35, P = 1.0 × 10−5) and colorectal adenoma (OR = 1.39, P = 1.6 × 10−4). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88–1.27).
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