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Identification and Validation of the Prognostic Impact of Metastatic Prostate Cancer Phenotypes

Published:February 23, 2022DOI:https://doi.org/10.1016/j.clgc.2022.02.008

      Introduction

      Castration-sensitive metastatic prostate cancer is heterogeneous. Our objective is to identify metastatic prostate cancer phenotypes and their prognostic impact on survival.

      Materials and Methods

      The National Cancer Database was queried. The Surveillance, Epidemiology, and End Results database was used for validation. Patterns were split into: nonregional lymph node, bone only, and visceral (any brain/liver/lung). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated for the univariate and multivariate Cox proportional hazards regression models, odds ratios were calculated, Kaplan-Meier curves were generated, and a nomogram of the multivariate regression model was created.

      Results

      The training set included 13,818 men; bone only was most common (n = 11,632, 84.2%), then nonregional lymph node (n = 1388, 10.0%), and any visceral (brain/liver/lung; n = 798, 5.8%). Risk of death was increased by metastases to a visceral organ versus nonregional lymph node (HR = 2.26; 95% CI [2.00, 2.56]), bone only metastases versus nonregional lymph node (HR = 1.57; 95% CI [1.43, 1.72]), T-stage 4 versus 1 (HR = 1.27; 95% CI [1.17, 1.36]), Grade Group 5 versus 1 (HR = 1.93; 95% CI [1.61, 2.31]), PSA > 20 ng/mL versus < 10 ng/mL (HR = 1.32; 95% CI [1.23, 1.42]), and age ≥ 80 versus < 50 (HR = 1.96; 95% CI [1.69, 2.29]). On internal validation, the model had C-indices 20.5%, 22.7%, and 14.6% higher than the current staging system for overall survival, 1-year, and 5-year survival, respectively.

      Conclusion

      We developed and validated prognostic metastatic prostate cancer phenotypes that can assist risk stratification to potentially personalize therapy. Our nomogram (https://tinyurl.com/prostate-met) may be used to predict survival.

      Keywords

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      References

        • Siegel RL
        • Miller KD
        • Jemal A.
        Cancer statistics, 2018.
        CA Cancer J Clin. 2018; 68: 7-30
        • Horn SR
        • Stoltzfus KC
        • Lehrer EJ
        • et al.
        Epidemiology of liver metastases.
        Cancer Epidemiol. 2020; 67101760
        • Ryan C
        • Stoltzfus KC
        • Horn S
        • et al.
        Epidemiology of bone metastases.
        Bone. 2020; 115783https://doi.org/10.1016/j.bone.2020.115783
        • Singh R
        • Stoltzfus KC
        • Chen H
        • et al.
        Epidemiology of synchronous brain metastases.
        Neurooncol Adv. 2020; 2: vdaa041https://doi.org/10.1093/noajnl/vdaa041
        • Tharp D
        • Nandana S.
        How prostate cancer cells use strategy instead of brute force to achieve metastasis.
        Cancers (Basel). 2019; 11: 1928
        • Lehrer EJ
        • Singh R
        • Wang M
        • et al.
        Safety and survival rates associated with ablative stereotactic radiotherapy for patients with oligometastatic cancer: a systematic review and meta-analysis.
        JAMA Oncol. 2021; 7: 92-106
        • Zaorsky NG
        • Liang M
        • Patel R
        • et al.
        Survival after palliative radiation therapy for cancer: the METSSS model.
        Radiother Oncol. 2021; 158: 104-111
        • Boffa DJ
        • Rosen JE
        • Mallin K
        • et al.
        Using the national cancer database for outcomes research: a review.
        JAMA Oncol. 2017; 3: 1722-1728
        • Mahal BA
        • Yang DD
        • Wang NQ
        • et al.
        Clinical and genomic characterization of low–prostate-specific antigen, high-grade prostate cancer.
        Eur Urol. 2018; 74: 146-154
        • Armstrong AJ
        • Garrett-Mayer ES
        • Yang YC
        • de Wit R
        • Tannock IF
        • Eisenberger M.
        A contemporary prognostic nomogram for men with hormone-refractory metastatic prostate cancer: a TAX327 study analysis.
        Clin Cancer Res. 2007; 13: 6396-6403
        • Budnik J
        • Suri J
        • Bates JE
        • Bylund KC
        • Milano MT.
        Prognostic significance of sites of visceral metastatic disease in prostate cancer: a population-based study of 12,180 patients.
        Clin Genitourin Cancer. 2019; 17: 260-267
        • Cui PF
        • Cong XF
        • Gao F
        • et al.
        Prognostic factors for overall survival in prostate cancer patients with different site-specific visceral metastases: a study of 1358 patients.
        World J Clin Cases. 2020; 8: 54-67
        • Gandaglia G
        • Abdollah F
        • Schiffmann J
        • et al.
        Distribution of metastatic sites in patients with prostate cancer: a population-based analysis.
        Prostate. 2014; 74: 210-216
        • Gandaglia G
        • Karakiewicz PI
        • Briganti A
        • et al.
        Impact of the site of metastases on survival in patients with metastatic prostate cancer.
        Eur Urol. 2015; 68: 325-334
        • Guo Y
        • Mao S
        • Zhang A
        • et al.
        Prognostic significance of young age and non-bone metastasis at diagnosis in patients with metastatic prostate cancer: a SEER population-based data analysis.
        J Cancer. 2019; 10: 556-567
        • Halabi S
        • Kelly WK
        • Ma H
        • et al.
        Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer.
        J Clin Oncol. 2016; 34: 1652-1659
        • Koo KC
        • Park SU
        • Kim KH
        • et al.
        Prognostic impacts of metastatic site and pain on progression to castrate resistance and mortality in patients with metastatic prostate cancer.
        Yonsei Med J. 2015; 56: 1206-1212
        • Mazzone E
        • Preisser F
        • Nazzani S
        • et al.
        Location of metastases in contemporary prostate cancer patients affects cancer-specific mortality.
        Clin Genitourin Cancer. 2018; 16 (e371): 376-384
        • Ost P
        • Decaestecker K
        • Lambert B
        • et al.
        Prognostic factors influencing prostate cancer-specific survival in non-castrate patients with metastatic prostate cancer.
        Prostate. 2014; 74: 297-305
        • Pond GR
        • Sonpavde G
        • de Wit R
        • Eisenberger MA
        • Tannock IF
        • Armstrong AJ.
        The prognostic importance of metastatic site in men with metastatic castration-resistant prostate cancer.
        Eur Urol. 2014; 65: 3-6
        • Shou J
        • Zhang Q
        • Wang S
        • Zhang D.
        The prognosis of different distant metastases pattern in prostate cancer: a population based retrospective study.
        Prostate. 2018; 78: 491-497
        • Whitney CA
        • Howard LE
        • Posadas EM
        • et al.
        In men with castration-resistant prostate cancer, visceral metastases predict shorter overall survival: what predicts visceral metastases? Results from the SEARCH database.
        Eur Urol Focus. 2017; 3: 480-486
        • Zhao F
        • Wang J
        • Chen M
        • et al.
        Sites of synchronous distant metastases and prognosis in prostate cancer patients with bone metastases at initial diagnosis: a population-based study of 16,643 patients.
        Clin Transl Med. 2019; 8: 30
        • Halabi S
        • Small EJ
        • Kantoff PW
        • et al.
        Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer.
        J Clin Oncol. 2003; 21: 1232-1237
        • Smaletz O
        • Scher HI
        • Small EJ
        • et al.
        Nomogram for overall survival of patients with progressive metastatic prostate cancer after castration.
        J Clin Oncol. 2002; 20: 3972-3982
      1. Damron TA, Morgan H, Prakash D, Grant W, Aronowitz J, Heiner J. Critical evaluation of Mirels' rating system for impending pathologic fractures. 2003; Heidelberg.

        • Maurer T
        • Eiber M
        • Schwaiger M
        • Gschwend JE.
        Current use of PSMA–PET in prostate cancer management.
        Nat Rev Urol. 2016; 13: 226-235
        • Soni PD
        • Hartman HE
        • Dess RT
        • et al.
        Comparison of population-based observational studies with randomized trials in oncology.
        J Clin Oncol. 2019; 37: 1209-1216
        • Balachandran VP
        • Gonen M
        • Smith JJ
        • Dematteo RP.
        Nomograms in oncology: more than meets the eye.
        Lancet Oncol. 2015; 16: e173-e180