On the diagnosis of early stage Prostate Cancer with an emphasis on Prostate Cancer Gene 3 (PCA3) and Real-Time Elastography (RTE)
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Aims: To investigate real-time elastography (RTE} and prostate cancer gene 3 (PCA3} to see if these emerging markers/methods could contribute to a faster and more precise diagnosis and also to investigate the possibility of a better selection of patients in need of prostate biopsies. Material and methods: Paper I: 40 consecutive patients planned for radical prostatectomy (RP} was investigated with RTE and PCA3 prior of RP. The results were compared to the whole-mount section pathology of the RP specimen. Paper II-IV: 127 consecutive patients planned for initial prostate biopsies were included. They were first examined with DRE for determination of clinical stage and for the prostatic massage needed before PCA3 analysis. Then they were examined with RTE and RTE targeted biopsies were obtained from hard lesions. Then a transrectal ultrasound guided systematic 10-core biopsy was performed in all patients. Results: Paper I: Using PCA3 score with cut off of 35, 26 patients had a positive PCA3 test and 11 patients had a false negative test. The largest tumour with correct location was found in 73% and at least one tumour was found in 89%. Only one patient had both a negative RTE and PCA3 score leading to a total detection rate of 97%. Paper II: 64 patients were diagnosed with PC in the initial biopsy setting. The RTE targeted biopsies had a higher frequency of positive cores and also a trend towards a higher fraction of PC in the targeted biopsy cores than in the cores from the systematic biopsies (42% vs. 33%}. RTE was found to be an independent marker for the detection of high-risk PC. Per region of interest (ROI) a negative predictive value (NPV) of 97% was found for high grade PC with Gleason grade 4+3, score 7 and higher. Paper III: The systematic initial biopsies were used for the analyses. PC was diagnosed in 59 patients. PCA3 was tested for the cut-off values 21 and 35. The sensitivity/specificity was 71%/ 72% using 35 as cut-off and 81%/55% using 21 as cut-off respectively. Hansen's nomogram was valid for our cohort. PCA3 contributed significantly to the performance of the nomogram, a threshold value of 20 as biopsy decision seems to be safe. Paper IV: This paper also includes a follow-up period with a mean observation time of 46.7 (range 41- 55) months. Included are the results from the initial biopsies and also the results of eventual repeat biopsies. If both RTE and PCA3 are negative there is a low probability of detecting aggressive PC. The combined use of RTE and PCA3 lead to a NPV of 90% for the group of intermediate- and high-risk PC together, for the high-risk group NPV was 100%. Conclusions: RTE has the ability of detecting PC and can be used for detection and also for targeted biopsies. PCA3 can be used in an initial biopsy setting and it contributes significantly to the area under the curve when applied to a nomogram. The combined use of PCA3 and RTE is better than the methods used alone.
Has partsPaper I: Nygard Y, Haukaas SA, Waage JE, Halvorsen OJ, Gravdal K, Frugard J, Akslen LA, Beisland C. Combination of real-time elastography and urine prostate cancer gene 3 (PCA3) detects more than 97% of significant prostate cancers. Scand j Ural. 2013 Jun;47(3):211-216. Full text not available in BORA due to publisher restrictions. The article is available at: http://dx.doi.org/10.3109/00365599.2012.727859
Paper II: Nygard Y, Haukaas SA, Halvorsen OJ, Gravdal K, Frugard J, Akslen LA, Beisland C. A positive real-time elastography is an independent marker for detection of high- risk prostate cancers in the primary biopsy setting. BjU Int. 2014 May;113(5b):E90-97. The article is available in the main thesis. The article is also available at: http://dx.doi.org/10.1111/bju.12401
Paper III: Nygard Y, Haukaas SA, Eide GE, Halvorsen OJ, Gravdal K, Frugard J, Akslen LA, Beisland C. Prostate cancer antigen-3 (PCA3) and PCA3-based nomograms in the diagnosis of prostate cancer: An external validation of Hansen's nomogram on a Norwegian cohort. Scand J Urol. 2015 Feb;49(1):8-15. Full text not available in BORA due to publisher restrictions. The article is available at: http://dx.doi.org/10.3109/21681805.2014.949841
Paper IV: Nygard Y, Haukaas SA, Halvorsen OJ, Gravdal K, Frugard J, Akslen LA, Beisland C. A positive Real-Time Elastograpy (RTE) combined with a Prostate Cancer Gene 3 (PCA3) score above 35 convey a high probability of intermediate- or high-risk prostate cancer in patient admitted for primary prostate biopsy. BMC Urol 2016 Jul 8;16(1):39. The article is available at: http://hdl.handle.net/1956/12536