DNA Ploidy as a Potential Adjunct Prognostic Marker of Low-Risk Prostate Cancer Progression after Radical Prostatectomy
Urology Journal,
Vol. 21 No. 02 (2024),
24 March 2024
,
Page 80-86
https://doi.org/10.22037/uj.v20i.7324
Abstract
Purpose: Post prostatectomy PSA kinetics and General Grade Groups (GGG) are the strongest prognostic markers
of biochemical recurrence (BCR) and prostate cancer (PCa)-specific mortality after radical prostatectomy. Despite
having low-risk PCa, some patients will experience BCR, for some, clinically significant BCR. There is a need for
an objective prognostic marker at the time of prostatectomy to improve risk stratification within this population. In
this study, we investigated the prognostic potential of DNA ploidy.
Materials and Methods: Prostatectomy samples from 97 patients with GGG1 and GGG2 with a low-risk
CAPRA-S score were included in this study. PCa tissue with the worst Gleason pattern underwent tissue disaggregation, cell isolation and staining with a DNA stoichiometric stain. Using image cytometry, DNA ploidy was
measured and a Ploidy Score (PS) was generated.
Results: Among the 97 patients, 79 had no BCR, 18 experienced BCR, of which 14 had a PSA doubling time
(PSA-DT) >1 year (low-risk group) and 4 had a PSA-DT of <1 year (high-risk group). Using Logistic regression
analysis, only pathological T stage (pT) and PS independently predicted BCR with PS being the most significant
(p = 0.001). The number of aneuploid cells was significantly higher in the high-risk group compared to the other
groups (p = 1.7x10-11). PS combined with GGG diagnosis further stratified risk groups of biochemical recurrence
free survival within CAPRA-S low-risk cohort.
Conclusion: DNA ploidy is an independent prognostic marker of BCR in low-risk PCa after radical prostatectomy,
which could early on identify potentially aggressive PCa recurrences and introduce a more personalized approach
to salvage treatments.
- prostate cancer, DNA ploidy, biochemical recurrence, image cytometry, prognostic marker
How to Cite
References
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018;68(6). doi:10.3322/caac.21492
Welch HG, Black WC. Overdiagnosis in cancer. Journal of the National Cancer Institute. 2010;102(9). doi:10.1093/jnci/djq099
Grimm P, Billiet I, Bostwick D, et al. Comparative analysis of prostate- specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU International. 2012;109(SUPPL. 1):22-29. doi:10.1111/j.1464-410X.2011.10827.x
Veloso SG, Lima MF, Salles PG, Berenstein CK, Scalon JD, Bambirra EA. Interobserver agreement of Gleason score and modified Gleason score in needle biopsy and in surgical specimen of prostate cancer. International Braz J Urol. 2007;33(5):639-646. doi:10.1590/s1677- 55382007000500005
Brajtbord JS, Leapman MS, Cooperberg MR. The CAPRA Score at 10 Years: Contemporary Perspectives and Analysis of Supporting Studies. European Urology. 2017;71(5):705-709. doi:10.1016/j.eururo.2016.08.065
Cooperberg MR, Hilton JF, Carroll PR. The CAPRA-S score: A straightforward tool for improved prediction of outcomes after radical prostatectomy. Cancer. 2011;117(22):5039-5046. doi:10.1002/cncr.26169
van den Broeck T, van den Bergh RCN, Arfi N, et al. Prognostic Value of Biochemical Recurrence Following Treatment with Curative Intent for Prostate Cancer: A Systematic Review. European Urology. 2019;75(6):967- 987. doi:10.1016/j.eururo.2018.10.011
Tilki D, Preisser F, Graefen M, Huland H, Pompe RS. External Validation of the European Association of Urology Biochemical Recurrence Risk Groups to Predict Metastasis and Mortality After Radical Prostatectomy in a European Cohort. European Urology. 2019;75(6):896-900. doi:10.1016/j.eururo.2019.03.016
Spratt DE, Yousefi K, Deheshi S, et al. Individual Patient-Level Meta- Analysis of the Performance of the Decipher Genomic Classifier in High- Risk Men After Prostatectomy to Predict Development of Metastatic Disease. Journal of Clinical Oncology. 2017;35(18):1991-1998. doi:10.1200/JCO.2016.70.2811
Fine ND, LaPolla F, Epstein M, Loeb S, Dani H. Genomic classifiers for treatment selection in newly diagnosed prostate cancer. BJU International. 2019;124(4):578-586. doi:10.1111/bju.14799
Wei L, Wang J, Lampert E, et al. Intratumoral and Intertumoral Genomic Heterogeneity of Multifocal Localized Prostate Cancer Impacts Molecular Classifications and Genomic Prognosticators. European Urology. 2017;71(2):183-192. doi:10.1016/j.eururo.2016.07.008
Danielsen HE, Pradhan M, Novelli M. Revisiting tumour aneuploidy — the place of ploidy assessment in the molecular era. Nature Reviews Clinical Oncology. 2016;13(5):291-304. doi:10.1038/nrclinonc.2015.208
Chunduri NK, Storchová Z. The diverse consequences of aneuploidy.
Nature Cell Biology. 2019;21(1):54-62. doi:10.1038/s41556-018-0243-8
Böcking A, Tils M, Schramm M, Dietz J, Biesterfeld S. DNA-cytometric grading of prostate cancer Systematic review with descriptive data analysis. Pathology Discovery. 2014;2(1):7. doi:10.7243/2052-7896-2-7
Authors. 2013
Lennartz M, Minner S, Brasch S, et al. The Combination of DNA Ploidy Status and PTEN/6q15 Deletions Provides Strong and Independent Prognostic Information in Prostate Cancer. Clinical cancer research: an official journal of the American Association for Cancer Research. 2016;22(11):2802-2811. doi:10.1158/1078-0432.CCR-15-0635
Stopsack KH, Whittaker CA, Gerke TA, et al. Aneuploidy drives lethal progression in prostate cancer. Proceedings of the National Academy of Sciences of the United States of America. 2019;116(23):11390-11395. doi:10.1073/pnas.1902645116
Ben-David U, Amon A. Context is everything: aneuploidy in cancer. Nature Reviews Genetics. 2020;21(1):44-62. doi:10.1038/s41576-019-0171-x
Carmichael MJ, Veltri RW, Partin AW, Miller MC, Walsh PC, Epstein JI. Deoxyribonucleic acid ploidy analysis as a predictor of recurrence following radical prostatectomy for stage T2 disease. The Journal of urology. 1995;153(3 Pt 2):1015—1019. doi:10.1097/00005392- 199503001-00029
Pretorius ME, Wæhre H, Abeler VM, et al. Large scale genomic instability as an additive prognostic marker in early prostate cancer. Cellular Oncology. 2009;31(4):251-259. doi:10.3233/CLO-2009-0463
Pound CR. Natural History of Progression After PSA Elevation Following Radical Prostatectomy. JAMA. 1999;281(17):1591. doi:10.1001/jama.281.17.1591
Garner DM, Todorovic C, Lee WE. Cytological stain composition and method of use. US patent No. 2,006,199,243. 2005.
Doudkine A, Macaulay C, Poulin N, Palcic B. Nuclear texture measurements in image cytometry. Pathologica. 1995;87(3):286-299.
Lau WK, Bergstralh EJ, Blute ML, Slezak JM, Zincke H. Radical prostatectomy for pathological Gleason 8 or greater prostate
cancer: influence of concomitant pathological variables. The Journal of urology. 2002;167(1):117-122.
Bantis A, Patsouris E, Gonidi M, et al. Telomerase RNA expression and DNA ploidy as prognostic markers of prostate carcinomas. Tumori. 2009;95(6):744-752. doi:10.1177/030089160909500618
Swanson GP, Chen W, Speights VO. Failure of Ploidy and Proliferative Fraction to Predict Long-Term Outcome After Prostatectomy. World Journal of Oncology. 2018;9(3):69-73. doi:10.14740/wjon1111w
Blute ML, Bergstralh EJ, Iocca A, Scherer B, Zincke H. Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy. Journal of Urology. 2001;165(1):119-125. doi:10.1097/00005392-200101000-00030
Hveem TS, Kleppe A, Vlatkovic L, et al. Chromatin changes predict recurrence after radical prostatectomy. British journal of cancer. 2016;114(11):1243-1250. doi:10.1038/bjc.2016.96
Lau WK, Blute ML, Bostwick DG, Weaver AL, Sebo TJ, Zincke H. Prognostic factors for survival of patients with pathological Gleason score 7 prostate cancer: differences in outcome between primary Gleason grades 3 and 4. The Journal of urology. 2001;166(5):1692-1697.
Toussi A, Stewart-Merrill SB, Boorjian SA, et al. Standardizing the Definition of Biochemical Recurrence after Radical Prostatectomy—What Prostate Specific Antigen Cut Point Best Predicts a Durable Increase and Subsequent Systemic Progression? Journal of Urology. 2016;195(6):1754- 1759. doi:10.1016/j.juro.2015.12.075
- Abstract Viewed: 512 times
- 7324/pdf Downloaded: 285 times