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The prognostic value of pain in castration-sensitive prostate cancer

Prostate Cancer and Prostatic Diseases volume 23, pages 654–660 (2020)Cite this article

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Abstract

Background

Cancer-related pain, usually associated with bone metastases, is a frequent and debilitating morbidity in patients with prostate cancer. To date there are only limited data regarding the prognostic role of pain in men with metastatic castration-sensitive prostate cancer (mCSPC). The objective of our analysis was to assess if the presence of pain can be considered an independent prognostic factor in mCSPC patients.

Methods

A retrospective analysis was performed on patients with mCSPC referring to six oncology centers in Italy. Clinical and pathological features were recorded. Patients were considered to have pain if this was reported within the patient’s file or in case of a chronic analgesic therapy was found among the concomitant medications. Survivals were estimated by the Kaplan–Meier method, and compared across groups using the log-rank test. Cox proportional hazard models, stratified according to the baseline characteristics, were used to estimate hazard ratios for overall survival (OS). All the variables were significant if p < 0.05.

Results

Data about pain were available for 365 cases and pain was present in 34.8% of patients. Pain was mainly associated with high value of prostate-specific antigen, metastatic bone extension regardless of the site, and lymph node involvement. mCSPC patients with pain had in most of the cases high-volume or Hr disease, and significant shorter OS (27.0 vs. 58.2 months, p < 0.001) and PFS (10.1 vs. 17.4 months, p < 0.001) compared to those without pain. The negative impact of pain on OS remained significant even if adjusted for CHAARTED or LATITUDE classification, and other significant baseline prognostic factors.

Conclusions

This analysis supports the poor prognostic role of cancer-related pain in the setting of mCSPC patients. A prospective validation is required.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.

    Article  Google Scholar 

  2. Weiner AB, Matulewicz RS, Eggener SE, Schaeffer EM. Increasing incidence of metastatic prostate cancer in the United States (2004-2013). Prostate Cancer Prostatic Dis. 2016;19:395–7.

    Article  CAS  Google Scholar 

  3. Iacovelli R, Ciccarese C, Mosillo C, Bimbatti D, Fantinel E, Stefani L, et al. Comparison between prognostic classifications in de novo metastatic hormone sensitive prostate cancer. Target Oncol. 2018;13:649–55.

    Article  Google Scholar 

  4. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N. Engl J Med. 2015;373:737–46.

    Article  CAS  Google Scholar 

  5. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, 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;387:1163–77.

    Article  CAS  Google Scholar 

  6. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N. Engl J Med. 2017;377:352–60.

    Article  CAS  Google Scholar 

  7. James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N. Engl J Med. 2017;377:338–51.

    Article  CAS  Google Scholar 

  8. Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N. Engl J Med. 2019;381:121–31.

    Article  CAS  Google Scholar 

  9. Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N. Engl J Med. 2019;381:13–24.

    Article  CAS  Google Scholar 

  10. Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, et al. ARCHES: a randomized, phase iii study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019;37:2974–86.

    Article  CAS  Google Scholar 

  11. Halabi S, Vogelzang NJ, Kornblith AB, Ou SS, Kantoff PW, Dawson NA, et al. Pain predicts overall survival in men with metastatic castration-refractory prostate cancer. J Clin Oncol. 2008;26:2544–9.

    Article  Google Scholar 

  12. Gotay CC, Kawamoto CT, Bottomley A, Efficace F. The prognostic significance of patient-reported outcomes in cancer clinical trials. J Clin Oncol. 2008;26:1355–63.

    Article  Google Scholar 

  13. 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;13:6396–403.

    Article  CAS  Google Scholar 

  14. Miller K, Carles J, Gschwend JE, Van Poppel H, Diels J, Brookman-May SD. The phase 3 COU-AA-302 study of abiraterone acetate plus prednisone in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: stratified analysis based on pain, prostate-specific antigen, and Gleason score. Eur Urol. 2018;74:17–23.

    Article  CAS  Google Scholar 

  15. Armstrong AJ, Lin P, Higano CS, Sternberg CN, Sonpavde G, Tombal B, et al. Development and validation of a prognostic model for overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer. Ann Oncol. 2018;29:2200–7.

    Article  CAS  Google Scholar 

  16. Halabi S, Lin CY, Small EJ, Armstrong AJ, Kaplan EB, Petrylak D, et al. Prognostic model predicting metastatic castration-resistant prostate cancer survival in men treated with second-line chemotherapy. J Natl Cancer Inst. 2013;105:1729–37.

    Article  CAS  Google Scholar 

  17. Cella D, Traina S, Li T, Johnson K, Ho KF, Molina A, et al. Relationship between patient-reported outcomes and clinical outcomes in metastatic castration-resistant prostate cancer: post hoc analysis of COU-AA-301 and COU-AA-302. Ann Oncol. 2018;29:392–7.

    Article  CAS  Google Scholar 

  18. Delanoy N, Robbrecht D, Fizazi K, Mercier F, Sartor O, De Wit R, et al. Pain progression at initiation of chemotherapy in metastatic castration-resistant prostate cancer (mCRPC) is associated with a poor prognosis: a post-hoc analysis of FIRSTANA. Ann Oncol. 2019;30:v335–v336.

    Article  Google Scholar 

  19. Glass TR, Tangen CM, Crawford ED, Thompson I. Metastatic carcinoma of the prostate: identifying prognostic groups using recursive partitioning. J Urol. 2003;169:164–9.

    Article  CAS  Google Scholar 

  20. Gravis G, Boher JM, Fizazi K, Joly F, Priou F, Marino P, et al. Prognostic factors for survival in noncastrate metastatic prostate cancer: validation of the glass model and development of a novel simplified prognostic model. Eur Urol. 2015;68:196–204.

    Article  Google Scholar 

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Authors and Affiliations

  1. Medical Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Roberto Iacovelli, Chiara Ciccarese & Giampaolo Tortora

  2. Department of Medical Oncology, Santa Chiara Hospital, 38112, Trento, Italy

    Orazio Caffo & Francesca Maines

  3. Department of Medical Oncology, Scientific Institute Romagnolo for the Study and Treatment of Cancer (IRST) IRCCS, Meldola, Italy

    Ugo De Giorgi & Chiara Casadei

  4. SC Oncologia, Ospedale Cardinal Massaia, Asti, Italy

    Marcello Tucci

  5. Medical Oncology Unit, Azienda Ospedaliera Santa Maria di Terni, Terni, Italy

    Claudia Mosillo

  6. Medical Oncology Unit 1, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy

    Davide Bimbatti & Francesco Pierantoni

  7. Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Turin, Italy

    Consuelo Buttigliero

  8. Medical Oncology Unit, Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, Italy

    Michele Milella

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  1. Roberto Iacovelli
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Corresponding author

Correspondence to Roberto Iacovelli.

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Conflict of interest

R.I.: advisory board member for Pfizer, Janssen, Sanofi, IPSEN, MSD, and Novartis. O.C.: advisory board member/speaker for Pfizer, Janssen, IPSEN, and Astellas. U.D.G.: advisory board or consultant fees from Merck Sharp & Dohme, Bristol Myers Squibb, Janssen, Astellas, Sanofi, Bayer, Pfizer, Ipsen, Novartis, Pharmamar and Institutional research grant from Astrazeneca, Sanofi, and Roche. C.B.: advisory board member for Janssen. G.T.: advisory board member for BMS and Novartis. Chiara Ciccarese (occasional consultant of IPSEN and Merck), M.T., C.M., D.B., F.P., F.M., Chiara Casadei, and M.M. declare that they have no conflict of interest.

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Iacovelli, R., Ciccarese, C., Caffo, O. et al. The prognostic value of pain in castration-sensitive prostate cancer. Prostate Cancer Prostatic Dis 23, 654–660 (2020). https://doi.org/10.1038/s41391-020-0255-x

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