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Minimal Residual Disease Defines the Risk and Time to Biochemical Failure in Patients with pT2 and pT3a Prostate Cancer Treated with Radical Prostatectomy: an Observational Prospective Study

Nigel P Murray, Socrates Aedo, Cynthia Fuentealba, Eduardo Reyes, Anibal Salazar, Marco Antonio Lopez, Simona Minzer, Shenda Orrego, Eghon Guzman
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Abstract

Purpose: To compare Gleason score (GS), pathological stage, minimal residual disease (MRD) and outcome after prostatectomy radical for prostate cancer.

Methods and Patients: 290/357 men with GS 6 or 7 and pT2 or pT3a disease treated with radical prostatectomy participated. Blood and bone marrow were obtained one month after surgery. Circulating prostate cells (CPCs) were detected using differential gel centrifugation and immunocytochemistry with anti PSA, micro-metastasis were detected using immunocytochemistry with anti-PSA. Biochemical failure free survival (BFFS) and restricted mean survival times (RMST) were calculated according to GS and stage. MRD was classified as negative, patients only positive for micro-metastasis and patients positive for CPCs; BFFS and RMST were calculated according to MRD sub-type.

Results: GS7 (HR 3.03) and pT3a (HR 3.68) cancers were associated with a higher failure rate, shorter time to failure and associated with CPC positive MRD (p<0.001), while G6 and pT2 with MRD negative disease (p<0.001). Men with CPC (+) MRD were at high risk of early treatment failure; 15% BFFS at 10 years, RMST 3.0 years. Men positive for only micro-metastasis were at risk of late failure, 50% BFFS at 10 years, RMST 8.0 years compared with MRD negative patients; 80% BFFS at 10 years, RMST 9.0 years.

Conclusions: The sub-type of MRD identifies Gleason 6 pT2 patients with a poor prognosis and Gleason 7 pT3a patients with a good prognosis and could be used to classify men according to personal risk characteristics for the use of adjuvant treatment.

(244 words).


References

References:

Mottet, N., Bellmunt, J., Bolla, M. et al.: EAU-ESTRO-SIOG Guidelines on

Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with

Curative Intent. Eur Urol, 2011; 71: 618

Theiss M, Wirth MP, Manseck A, Frohmuller HG. Prognostic significance of capsular invasion and capsular penetration in patients with clinically localized prostate cancer undergoing radical prostatectomy. Prostate 1995; 27: 13-17

Shuford MD, Cookson MS, Chang SS, Shintani AK, Tsiatis A, Smith JA Jr et al. Adverse prognostic significance of capsular incision with radical retropubic prostatectomy. J Urol 2004; 172: 119-123

Maubon T, Branger N, Bastide C, Lonjon G, Harvey-Bryan KA, Validire P et al. Impact of the extent of extraprostatic extension defined by Epstein`s method in patients with negative surgical margins and negative lymph node invasion. Prostate Cancer Prostatic diseasde 2016; 19: 317-321

Jeong BC, Chalfin HJ, Lee SB, Feng Z, Epstien JI, Trock BJ et al. The relationship between the extent of extraprostatic extension and survival following radical prostatectomy. Eur Urol 2015; 67: 342-346

Ball MW. Partin AW, Epstein JI. Extent of extraprostatic extension independently influences biochemical recurrence free survival: evidence for further pT3 subclassification. Urology 2015; 85: 161-164

Edge S, Bryd D, Compton C et al. American Joint Committee on Cancer, American Cancer Society. AJCC Cancer Staging Manual, New York, NY, Springer-Verlag, 2010.

Epsteinn JI, Partin AW, Sauvageot J et al. Prediction of progression following radical prostatectomy. A multivariante analysis of 721 men with long term follow up. Am J surg Pathol 1996; 20: 286-292

Thompson IM, Valicenti RK, Albertsen P et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline. J Urol 2013; 190: 441-449

Murray NP, Aedo S, Fuentealba C, Reyes E, Salazar S. Minimum Residual Disease in Patients Post Radical Prostatectomy for Prostate Cancer: Theoretical Considerations, Clinical Implications and Treatment Outcome. Asian Pac J Cancer Prev 2018; 19 (1), 229-236

. Ma X, Xiao Z, Li X, et al. Prognostic role of circulating tumor cells and disseminated tumor cells in patients with prostate cancer: a systemic review and meta-analysis. Tumour Biol, 2014; 35: 5551-60

. Murray NP, Reyes E, Orellana N, et al. Secondary circulating prostate cells predict biochemical failure after radical prostatectomy and without evidence of disease. Sci World J, 2013; http://dx.doi.org/10.1155/2013/762064.

Morgan TM, Lange PH, Porter MP, et al. Disseminated tumor cells in prostate cancer patients after radical prostatectomy and without evidence of disease predicts biochemical recurrence. Clin Cancer Res, 2009; 15: 677-83.

Partin AW, Mangold LA, Lamm DM, et al (2001). Contemporary update of prostate cancer staging nomograms (Partin tables) for the new millenium. J Urol, 58, 843

Borgen E, Naume B, Nesland JM, et al (1999). Standardization of the immunocytochemical detection of cancer cells in BM and blood. I. Establishment of objective criteria for the evaluation of immunostained cells. Cytotherapy, 1999; 1: 377–88.

Murray NP, Reyes E, Tapia P, et al. Redefining micrometastasis in prostate cancer- a comparison of circulating prostate cells, bone marrow disseminated tumor cells and micrometastasis: Implications in determining local or systemic treatment for biochemical failure after radical prostatectomy. Int J Mol Med, 2012; 30: 896-904

Rosner B. Fundametals of biostatistics. Seventh Edition. Boston: Cengaje Learning; 2010. 859 p.

. Cleves M, Gutierrez R, Gould W, Mrachenko Y. An introduction to survival analysis using stata. Third Edition. Texas: Stata Press; 2010. 412p.

. Royston P, Lambert PC. Flexible parametric survival analysis using stata: beyond the cox model. Texas: Stata Press; 2011. pp:347.

. Royston P, Parmar MK. Restricted mean survival time: an alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome. BMC Med Res Methodol. 2013; 13: 152.

. A`Hern RP. Restricted mean survival time: An obligatory end point for time to event analysis in cancer trials? J Clin Oncol 2016; 34: 3474-3476

. Harrell FE, Jr. Regression Modeling Strategies with Applications to Linear Models, Logistic Regression, and Survival Analysis. New York: Springer-Verlag; 2001

Harrell FE, Jr., Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. JAMA. 1982;247(18):2543-6.

. Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 2005; 29: 1228-1242

. Berg KD, Thomsen FB, Nerstrom C, Roder MA, Iversen P, Toft BG, Vainer B, Brasso K The impact of the 2005 ISUP consensus guidelines on Gleason glading-a matched pair analysis. BJU Int 2016; 117: 883-889 doi: 10.1111/bju.13439

. Thomsen FB, Folkvalion Y, Brasso K, Loeb S, Robinson D, Egevad L, Stattin P. Prognostic implications of 2005 Gleason grade modification. Population based study of biochemical recurrence following radical prostatectomy. J Surg Oncol 2016; 114: 664-670 doi: 10.1002/jso.24408

. Moreno JG, Croce CM, Fischer R, Monne M, Vihko P, Mulholland SG, Gomella LG. Detection of hematogenous micrometastasis in patients with prostate cancer. Cancer Res. 1992;52(21):6110-2

. Gundem G, Van Loo P, Kremeyer B, Alexandrov LB, Tubio JMC, Papaemmanuil E et al. The Evolutionary History of Lethal Metastatic Prostate Cancer. Nature. 2015; 520: 353–357 doi: 10.1038/nature14347

.Bearden JD, Ratkin GA, Coltman CA. Comparison of the diagnostic value of bone marrow biopsy and bone marrow aspiration in neoplastic disease. J Clin Pathol 1974; 27: 738-740

. Chandra S, Chandra H. Comparison of bone marrow aspirate cytology, touch imprint cytology and trephine biopsy for bone marrow evaluation. Haematology Reports 2011; 3: e22 doi: 10.4081/hr.2011.e22




DOI: http://dx.doi.org/10.22037/uj.v0i0.5174

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