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Characterization of Differences Between Prostate Cancer Patients Presenting with De Novo Versus Primary Progressive Metastatic Disease: Beyond the Abstract

Prostate cancer remains the most common non-cutaneous cancer among men and a cause of significant mortality and morbidity. Despite the widespread prevalence of prostate cancer, only 4%-5% of patients with prostate cancer will have metastatic disease as their initial presentation which we have termed de novo, dn.1 The remaining prostate cancer patients represent the primary progressive group (pp) who presents with metastatic disease after prior multimodality treatment intended for cure. The GETUG-AFU-15,2 CHAARTED,3 STAMPEDE, and LATITUDE trials included hormone-naive metastatic (dn and pp) prostate cancer patients. They showed that treatments usually reserved for the castrate resistant metastatic population are potentially more effective when used earlier in the disease state, during castrate sensitive metastatic disease. Although the above-mentioned studies did not stratify their metastatic patients into pp versus dn, they showed that the biology of the disease changes and so does the differential effect of various treatments in parallel.  We therefore sought to characterize differences between prostate cancer patients who present with dn metastatic disease versus those with pp metastatic disease. 

We conducted a retrospective cross-sectional analysis from a single institution of dn (38 patients) versus pp (52 patients) metastatic patients looking at patient characteristics, gleason scores, duration of hormone sensitivity, and treatment. We have found that patients with dn metastatic disease compared to those pp presented with lower hemoglobin level and albumin level, signifying a sicker population, had a higher PSA on presentation and were more likely than the pp metastatic patients to metastasize to lymph nodes. Interestingly, Gleason scores from biopsy at time of diagnosis were similar for both groups at around 8, though perhaps just indicative of the nature of the malignancy to metastasize. Moreover, dn patients had a statistically significant lower duration of hormone sensitivity (median 372 days) compared to pp patients (median 1613 days). Although we have a small number of patients in the study, we attempted to calculate overall survival as measured from the date of diagnosis for men with dn and from the date of diagnosis of metastasis for those with pp. The median survival in the dn group was 6.2 years while that in pp was 11.6 years (p=0.03). 

We believe our manuscript was the first to attempt a comparative description of differences between pp and dn metastatic prostate patients. We have shown that there are differences in characteristics, especially in duration of hormone sensitivity and possibly in survival, signifying a difference in tumor biology. This difference may also result in differential effects of various treatments used in metastatic prostate cancer patients if stratified to dn vs pp, raising the importance of possibly performing subset analysis by characterizing and subgrouping the patients in the GETUG-AFU-15, CHAARTED, STAMPEDE, and LATITUDE trials into dn versus pp. We also concluded that future trials may attempt to further characterize dn and pp patients into different stratification of groups rather than including all the populations together, as they have different biology.

Written by: Jeanny B. Aragon-Ching 

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References:

1.    Finianos A, Gupta K, Clark B, Simmens SJ, Aragon-Ching JB. Characterization of Differences Between Prostate Cancer Patients Presenting With De Novo Versus Primary Progressive Metastatic Disease. Clin Genitourin Cancer. 2017 Aug 31. pii:S1558-7673(17)30247-1. doi: 10.1016/j.clgc.2017.08.006. [Epub ahead of print] PubMed PMID: 28899723.

2.    Gravis G, Fizazi K, Joly F, Oudard S, Priou F, Esterni B, Latorzeff I, Delva R, Krakowski I, Laguerre B, Rolland F, Théodore C, Deplanque G, Ferrero JM, Pouessel D, Mourey L, Beuzeboc P, Zanetta S, Habibian M, Berdah JF, Dauba J, Baciuchka M, Platini C, Linassier C, Labourey JL, Machiels JP, El Kouri C, Ravaud A, Suc E, Eymard JC, Hasbini A, Bousquet G, Soulie M. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Feb;14(2):149-58. doi: 10.1016/S1470-2045(12)70560-0. Epub 2013 Jan 8. PubMed PMID: 23306100.

3.   Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate CancerProstate Cancer. N Engl J Med. 2015 Aug 20;373(8):737-46. doi: 10.1056/NEJMoa1503747. Epub 2015 Aug 5. PubMed PMID: 26244877; PubMed Central PMCID: PMC4562797.

4.   James ND, Sydes MR, Clarke NW, et al., Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial.  Lancet. 2016 Mar 19; 387(10024): 1163–1177.  doi: 10.1016/S0140-6736(15)01037-5. PMCID: PMC4800035

5.  Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY,Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, De Porre P, Kheoh T, Park YC, Todd MB, Chi KN; LATITUDE Investigators. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate CancerCastration-Sensitive Prostate Cancer. N Engl J Med. 2017 Jul 27;377(4):352-360. doi: 10.1056/NEJMoa1704174. Epub 2017 Jun 4. PubMed PMID: 28578607.Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, De Porre P, Kheoh T, Park YC, Todd MB, Chi KN; LATITUDE Investigators. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate CancerCastration-Sensitive Prostate Cancer. N Engl J Med. 2017 Jul 27;377(4):352-360. doi: 10.1056/NEJMoa1704174. Epub 2017 Jun 4. PubMed PMID: 28578607.