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Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

The outcome of prostate cancer patients treated with curative intent strongly depends on survival after metastatic progression

Authors: Mariarosa Pascale, Che Ngwa Azinwi, Barbara Marongiu, Gianfranco Pesce, Flavio Stoffel, Enrico Roggero

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Five-year survival in patients with localized prostate cancer (PCa) is nearly 100%, but metastatic disease still remains incurable. Clinical management of metastatic patients has become increasingly complex as novel therapeutic strategies have emerged. This study aims at evaluating the impact of the first metastatic progression on the outcome of PCa patients treated with curative intent.

Methods

The analysis was conducted using data of 913 cases of localized PCa diagnosed between 2000 and 2014. All patients were treated with curative surgery (N = 382) or radiotherapy (N = 531) with or without adjuvant therapy. All metastases were radiologically documented. The prognostic impact of the first site of metastasis on metastasis-free survival (MFS) and PCa-specific survival (PCaSS) was investigated by univariate and multivariate analyses.

Results

One hundred and thirty-six (14.9%) patients developed a metastatic hormone-sensitive PCa and had a median PCaSS of 50.4 months after first metastatic progression. Bone (N = 50, 36.8%) and LN or locoregional (N = 52, 38.2%) metastases occurred more frequently with a median PCaSS of 39.7 and 137 months respectively (p < 0.0001). Seven patients developed visceral metastasis only (5.1%; liver, lung, brain) and 27 (19.9%) concurrent metastases; this last group was associated with the worst survival with a median value of only 17 months. Thus, each subgroup exhibited a survival after metastasis significantly different from each other. In multivariate analysis the site of the first metastasis was an independent prognostic factor for PCaSS along with Gleason score at diagnosis. The correlation between survival and first site of metastasis was confirmed separately for each therapy subgroup. Median metastasis-free survival from primary diagnosis to first metastasis was not correlated with the first site of metastasis.

Conclusions

In non-metastatic PCa patients treated with curative intent, the PCa-specific survival time depends on the time after metastatic progression rather than the time from diagnosis to metastasis. Moreover, the site of first metastasis is an independent prognostic factor for PCaSS. Our data confirm that the first metastatic event may confer a differential prognostic impact and may help in identifying patient at high risk of death supporting the treatment-decision making process following metastatic progression.
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Literature
1.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed
2.
go back to reference DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS, Jemal A. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64:252–71.CrossRefPubMed DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS, Jemal A. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64:252–71.CrossRefPubMed
3.
go back to reference Arya M, Bott SR, Shergill IS, Ahmed HU, Williamson M, Patel HR. The metastatic cascade in prostate cancer. Surg Oncol. 2006;15:117–28.CrossRefPubMed Arya M, Bott SR, Shergill IS, Ahmed HU, Williamson M, Patel HR. The metastatic cascade in prostate cancer. Surg Oncol. 2006;15:117–28.CrossRefPubMed
4.
go back to reference Antonarakis ES, Feng Z, Trock BJ, Humphreys EB, Carducci MA, Partin AW, Walsh PC, Eisenberger MA. The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up. BJU Int. 2012;109:32–9.CrossRefPubMed Antonarakis ES, Feng Z, Trock BJ, Humphreys EB, Carducci MA, Partin AW, Walsh PC, Eisenberger MA. The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up. BJU Int. 2012;109:32–9.CrossRefPubMed
5.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, Partin AW. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005;294:433–9.CrossRefPubMed Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, Partin AW. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005;294:433–9.CrossRefPubMed
7.
go back to reference Gandaglia G, Abdollah F, Schiffmann J, Trudeau V, Shariat SF, Kim SP, Perrotte P, Montorsi F, Briganti A, Trinh Q, Karakiewicz PI, Sun M. Distribution of metastatic sites in patients with prostate cancer: a population-based analysis. Prostate. 2014;74:210–6.CrossRefPubMed Gandaglia G, Abdollah F, Schiffmann J, Trudeau V, Shariat SF, Kim SP, Perrotte P, Montorsi F, Briganti A, Trinh Q, Karakiewicz PI, Sun M. Distribution of metastatic sites in patients with prostate cancer: a population-based analysis. Prostate. 2014;74:210–6.CrossRefPubMed
8.
go back to reference Gandaglia G, Karakiewicz PI, Briganti A, Passoni NM, Schiffmann J, Trudeau V, Graefen M, Montorsi F, Sun M. Impact of the site of metastases on survival in patients with metastatic prostate cancer. Eur Urol. 2015;68:325–34.CrossRefPubMed Gandaglia G, Karakiewicz PI, Briganti A, Passoni NM, Schiffmann J, Trudeau V, Graefen M, Montorsi F, Sun M. Impact of the site of metastases on survival in patients with metastatic prostate cancer. Eur Urol. 2015;68:325–34.CrossRefPubMed
9.
go back to reference Ost P, Decaestecker K, Lambert B, Fonteyne V, Delrue L, Lumen N, Ameye F, De Meerleer G. Prognostic factors influencing prostate cancer-specific survival in non-castrate patients with metastatic prostate cancer. Prostate. 2014;74:297–305. Ost P, Decaestecker K, Lambert B, Fonteyne V, Delrue L, Lumen N, Ameye F, De Meerleer G. Prognostic factors influencing prostate cancer-specific survival in non-castrate patients with metastatic prostate cancer. Prostate. 2014;74:297–305.
10.
go back to reference James ND, Spears MR, Clarke NW, Dearnaley DP, De Bono JS, Gale J, Hetherington J, Hoskin PJ, Jones RJ, Laing R, Lester JF, McLaren D, Parker CC, Parmar MKB, Ritchie AWS, Russel JM, Strebel RT, Thalmann GN, Mason MD, Sydes MR. Survival with newly diagnosed metastatic prostate cancer in the “Docetaxel era”: data from 917 patients in the control arm of the STAMPEDE trial (MRC PR08, CRUK/06/019). Eur Urol. 2015;67:1028–38.CrossRefPubMed James ND, Spears MR, Clarke NW, Dearnaley DP, De Bono JS, Gale J, Hetherington J, Hoskin PJ, Jones RJ, Laing R, Lester JF, McLaren D, Parker CC, Parmar MKB, Ritchie AWS, Russel JM, Strebel RT, Thalmann GN, Mason MD, Sydes MR. Survival with newly diagnosed metastatic prostate cancer in the “Docetaxel era”: data from 917 patients in the control arm of the STAMPEDE trial (MRC PR08, CRUK/06/019). Eur Urol. 2015;67:1028–38.CrossRefPubMed
11.
go back to reference Koo KC, Park SU, Kim KH, Rha KH, Hong SJ, Yang SC, Chung BH. Prognostic impacts of metastatic site and pain on progression to castrate resistance and mortality in patients with metastatic prostate cancer. Yonsei Med J. 2015;56:1206–12.CrossRefPubMedPubMedCentral Koo KC, Park SU, Kim KH, Rha KH, Hong SJ, Yang SC, Chung BH. Prognostic impacts of metastatic site and pain on progression to castrate resistance and mortality in patients with metastatic prostate cancer. Yonsei Med J. 2015;56:1206–12.CrossRefPubMedPubMedCentral
12.
go back to reference Nini A, Gandaglia G, Fossati N, Suardi N, Cucchiara V, Dell’Oglio P, Cazzaniga W, Luzzago S, Montorsi F, Briganti A. Patterns of clinical recurrence of node-positive prostate cancer and impact on long-term survival. Eur Urol. 2015;68:777–84.CrossRefPubMed Nini A, Gandaglia G, Fossati N, Suardi N, Cucchiara V, Dell’Oglio P, Cazzaniga W, Luzzago S, Montorsi F, Briganti A. Patterns of clinical recurrence of node-positive prostate cancer and impact on long-term survival. Eur Urol. 2015;68:777–84.CrossRefPubMed
13.
go back to reference Halabi S, Kelly WK, Ma H, Zhou H, Solomon NC, Fizazi K, Tangen CM, Rosenthal M, Petrylak DP, Hussain M, Vogelzang NJ, Thompson IM, Chi KN, de Bono J, Armstrong AJ, Eisenberger MA, Fandi A, Li S, Araujo JC, Logothetis CJ, Quinn DI, Morris MJ, Higano CS, Tannock IF, Small EJ. Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer. J Clin Oncol. 2016;34:1652–9.CrossRefPubMedPubMedCentral Halabi S, Kelly WK, Ma H, Zhou H, Solomon NC, Fizazi K, Tangen CM, Rosenthal M, Petrylak DP, Hussain M, Vogelzang NJ, Thompson IM, Chi KN, de Bono J, Armstrong AJ, Eisenberger MA, Fandi A, Li S, Araujo JC, Logothetis CJ, Quinn DI, Morris MJ, Higano CS, Tannock IF, Small EJ. Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer. J Clin Oncol. 2016;34:1652–9.CrossRefPubMedPubMedCentral
14.
go back to reference Moschini M, Sharma V, Zattoni F, Quevedo JF, Davis BJ, Kwon E, Karnes RJ. Natural history of clinical recurrence patterns of lymph node-positive prostate cancer after radical prostatectomy. Eur Urol. 2016;69:135–42.CrossRefPubMed Moschini M, Sharma V, Zattoni F, Quevedo JF, Davis BJ, Kwon E, Karnes RJ. Natural history of clinical recurrence patterns of lymph node-positive prostate cancer after radical prostatectomy. Eur Urol. 2016;69:135–42.CrossRefPubMed
15.
go back to reference Goodman OBJ, Flaig TW, Molina A, Mulders PF, Fizazi K, Suttmann H, Li J, Kheoh T, de Bono JS, Scher HI. Exploratory analysis of the visceral disease subgroup in a phase III study of abiraterone acetate in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2014;17:34–9.CrossRefPubMed Goodman OBJ, Flaig TW, Molina A, Mulders PF, Fizazi K, Suttmann H, Li J, Kheoh T, de Bono JS, Scher HI. Exploratory analysis of the visceral disease subgroup in a phase III study of abiraterone acetate in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2014;17:34–9.CrossRefPubMed
16.
go back to reference Pezaro CJ, Omlin A, Lorente D, Nava Rodrigues D, Ferraldeschi R, Bianchini D, Mukherji D, Riisnaes R, Altavilla A, Crespo M, Tunariu N, de Bono JS, Attard G. Visceral disease in castration-resistant prostate cancer. Eur Urol. 2014;65:270–3.CrossRefPubMed Pezaro CJ, Omlin A, Lorente D, Nava Rodrigues D, Ferraldeschi R, Bianchini D, Mukherji D, Riisnaes R, Altavilla A, Crespo M, Tunariu N, de Bono JS, Attard G. Visceral disease in castration-resistant prostate cancer. Eur Urol. 2014;65:270–3.CrossRefPubMed
17.
go back to reference Evans CP, Higano CS, Keane T, Andriole G, Saad F, Iversen P, Miller K, Kim CS, Kimura G, Armstrong AJ, Sternberg CN, Loriot Y, de Bono J, Noonberg SB, Mansbach H, Bhattacharya S, Perabo F, Beer TM, Tombal B. The PREVAIL study: primary outcomes by site and extent of baseline disease for Enzalutamide-treated men with chemotherapy-naive metastatic castration-resistant prostate cancer. Eur Urol. 2016;70:675–83.CrossRefPubMed Evans CP, Higano CS, Keane T, Andriole G, Saad F, Iversen P, Miller K, Kim CS, Kimura G, Armstrong AJ, Sternberg CN, Loriot Y, de Bono J, Noonberg SB, Mansbach H, Bhattacharya S, Perabo F, Beer TM, Tombal B. The PREVAIL study: primary outcomes by site and extent of baseline disease for Enzalutamide-treated men with chemotherapy-naive metastatic castration-resistant prostate cancer. Eur Urol. 2016;70:675–83.CrossRefPubMed
18.
go back to reference Shao Y-HJ, Kim S, Moore DF, Shih W, Lin Y, Stein M, Kim IY, Lu-Yao GL. Cancer-specific survival after metastasis following primary radical prostatectomy compared with radiation therapy in prostate cancer patients: results of a population-based, propensity score-matched analysis. Eur Urol. 2014;65:693–700.CrossRefPubMed Shao Y-HJ, Kim S, Moore DF, Shih W, Lin Y, Stein M, Kim IY, Lu-Yao GL. Cancer-specific survival after metastasis following primary radical prostatectomy compared with radiation therapy in prostate cancer patients: results of a population-based, propensity score-matched analysis. Eur Urol. 2014;65:693–700.CrossRefPubMed
19.
go back to reference Barekati Z, Radpour R, Lu Q, Bitzer J, Zheng H, Toniolo P, Lenner P, Zhong XY. Methylation signature of lymph node metastases in breast cancer patients. BMC Cancer. 2012;12:244.CrossRefPubMedPubMedCentral Barekati Z, Radpour R, Lu Q, Bitzer J, Zheng H, Toniolo P, Lenner P, Zhong XY. Methylation signature of lymph node metastases in breast cancer patients. BMC Cancer. 2012;12:244.CrossRefPubMedPubMedCentral
20.
go back to reference Briganti A, Passoni NM, Abdollah F, Nini A, Montorsi F, Karnes RJ. Treatment of lymph node-positive prostate cancer: teaching old dogmas new tricks. Eur Urol. 2014;65:26–8.CrossRefPubMed Briganti A, Passoni NM, Abdollah F, Nini A, Montorsi F, Karnes RJ. Treatment of lymph node-positive prostate cancer: teaching old dogmas new tricks. Eur Urol. 2014;65:26–8.CrossRefPubMed
21.
go back to reference Gundem G, Van Loo P, Kremeyer B, Alexandrov LB, Tubio JM, Papaemmanuil E, Brewer DS, Kallio HM, Högnäs G, Annala M, Kivinummi K, Goody V, Latimer C, O'Meara S, Dawson KJ, Isaacs W, Emmert-Buck MR, Nykter M, Foster C, Kote-Jarai Z, Easton D, Whitaker HC, Prostate ICGC, UK Group, Neal DE, Cooper CS, Eeles RA, Visakorpi T, Campbell PJ, McDermott U, Wedge DC, Bova GS. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520:353–7.CrossRefPubMedPubMedCentral Gundem G, Van Loo P, Kremeyer B, Alexandrov LB, Tubio JM, Papaemmanuil E, Brewer DS, Kallio HM, Högnäs G, Annala M, Kivinummi K, Goody V, Latimer C, O'Meara S, Dawson KJ, Isaacs W, Emmert-Buck MR, Nykter M, Foster C, Kote-Jarai Z, Easton D, Whitaker HC, Prostate ICGC, UK Group, Neal DE, Cooper CS, Eeles RA, Visakorpi T, Campbell PJ, McDermott U, Wedge DC, Bova GS. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520:353–7.CrossRefPubMedPubMedCentral
22.
go back to reference Pouessel D, Gallet B, Bibeau F, Avancès C, Iborra F, Sénesse P, Culine S. Liver metastases in prostate carcinoma: clinical characteristics and outcome. BJU Int. 2007;99:807–11.CrossRefPubMed Pouessel D, Gallet B, Bibeau F, Avancès C, Iborra F, Sénesse P, Culine S. Liver metastases in prostate carcinoma: clinical characteristics and outcome. BJU Int. 2007;99:807–11.CrossRefPubMed
23.
go back to reference Wang H, Li B, Zhang P, Yao Y, Chang J. Clinical characteristics and prognostic factors of prostate cancer with liver metastases. Tumour Biol. 2014;35:595–601.CrossRefPubMed Wang H, Li B, Zhang P, Yao Y, Chang J. Clinical characteristics and prognostic factors of prostate cancer with liver metastases. Tumour Biol. 2014;35:595–601.CrossRefPubMed
24.
go back to reference Egevad L, Granfors T, Karlberg L, Bergh A, Stattin P. Prognostic value of the Gleason score in prostate cancer. BJU Int. 2002;89:538–42.CrossRefPubMed Egevad L, Granfors T, Karlberg L, Bergh A, Stattin P. Prognostic value of the Gleason score in prostate cancer. BJU Int. 2002;89:538–42.CrossRefPubMed
25.
go back to reference Stamey TA, McNeal JE, Yemoto CM, Sigal BM, Johnstone IM. Biological determinants of cancer progression in men with prostate cancer. JAMA. 1999;281:1395–400.CrossRefPubMed Stamey TA, McNeal JE, Yemoto CM, Sigal BM, Johnstone IM. Biological determinants of cancer progression in men with prostate cancer. JAMA. 1999;281:1395–400.CrossRefPubMed
26.
go back to reference Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989;8:98–101.PubMed Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989;8:98–101.PubMed
27.
go back to reference Jacob K, Webber M, Benayahu D, Kleinman HK. Osteonectin promotes prostate cancer cell migration and invasion: a possible mechanism for metastasis to bone. Cancer Res. 1999;59:4453–7.PubMed Jacob K, Webber M, Benayahu D, Kleinman HK. Osteonectin promotes prostate cancer cell migration and invasion: a possible mechanism for metastasis to bone. Cancer Res. 1999;59:4453–7.PubMed
28.
go back to reference Ewing J. Neoplastic diseases: a treatise on Tumours. Third ed. Philadelphia and London: W. B. Saunders Co. Ltd.; 1928. Ewing J. Neoplastic diseases: a treatise on Tumours. Third ed. Philadelphia and London: W. B. Saunders Co. Ltd.; 1928.
Metadata
Title
The outcome of prostate cancer patients treated with curative intent strongly depends on survival after metastatic progression
Authors
Mariarosa Pascale
Che Ngwa Azinwi
Barbara Marongiu
Gianfranco Pesce
Flavio Stoffel
Enrico Roggero
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3617-6

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