Skip to main content
Erschienen in: Cancer Causes & Control 3/2019

30.01.2019 | Original Paper

First-year weight loss with androgen-deprivation therapy increases risks of prostate cancer progression and prostate cancer-specific mortality: results from SEARCH

verfasst von: Kagan Griffin, Ilona Csizmadi, Lauren E. Howard, Gina-Maria Pomann, William J. Aronson, Christopher J. Kane, Christopher L. Amling, Matthew R. Cooperberg, Martha K. Terris, Jennifer Beebe-Dimmer, Stephen J. Freedland

Erschienen in: Cancer Causes & Control | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

We aimed to study the associations between androgen-deprivation therapy (ADT)-induced weight changes and prostate cancer (PC) progression and mortality in men who had undergone radical prostatectomy (RP).

Methods

Data from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort were used to study the associations between weight change approximately 1-year post-ADT initiation and metastases, castration-resistant prostate cancer (CRPC), all-cause mortality (ACM), and PC-specific mortality (PCSM) in 357 patients who had undergone RP between 1988 and 2014. We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) using covariate-adjusted Cox regression models for associations between weight loss, and weight gains of 2.3 kg or more, and PC progression and mortality post-ADT.

Results

During a median (IQR) follow-up of 81 (46–119) months, 55 men were diagnosed with metastases, 61 with CRPC, 36 died of PC, and 122 died of any cause. In multivariable analysis, weight loss was associated with increases in risks of metastases (HR 3.13; 95% CI 1.40–6.97), PCSM (HR 4.73; 95% CI 1.59–14.0), and ACM (HR 2.16; 95% CI 1.25–3.74) compared with mild weight gains of ≤ 2.2. Results were slightly attenuated but remained statistically significant in analyses that accounted for competing risks of non-PC death. Estimates for the associations between weight gains of ≥ 2.3 kg and metastases (HR 1.58; 95% CI 0.73–3.42), CRPC (HR 1.33; 95% CI 0.66–2.66), and PCSM (HR 2.44; 95% CI 0.84–7.11) were elevated, but not statistically significant.

Conclusions

Our results suggest that weight loss following ADT initiation in men who have undergone RP is a poor prognostic sign. If confirmed in future studies, testing ways to mitigate weight loss post-ADT may be warranted.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Foulkes SJ, Daly RM, Fraser SF (2017) The clinical importance of quantifying body fat distribution during androgen deprivation therapy for prostate cancer. Endocr Relat Cancer 24:R35–R48CrossRefPubMed Foulkes SJ, Daly RM, Fraser SF (2017) The clinical importance of quantifying body fat distribution during androgen deprivation therapy for prostate cancer. Endocr Relat Cancer 24:R35–R48CrossRefPubMed
2.
Zurück zum Zitat Galvao DA, Spry NA, Taaffe DR, Newton RU, Stanley J, Shannon T et al (2008) Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer. BJU Int 102:44–47CrossRefPubMed Galvao DA, Spry NA, Taaffe DR, Newton RU, Stanley J, Shannon T et al (2008) Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer. BJU Int 102:44–47CrossRefPubMed
3.
Zurück zum Zitat Nguyen PL, Alibhai SM, Basaria S, D’Amico AV, Kantoff PW, Keating NL et al (2015) Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol 67:825–836CrossRefPubMed Nguyen PL, Alibhai SM, Basaria S, D’Amico AV, Kantoff PW, Keating NL et al (2015) Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol 67:825–836CrossRefPubMed
4.
Zurück zum Zitat Hart NH, Galvão DA, Newton RU (2017) Exercise medicine for advanced prostate cancer. Cur Opin Support Palliat Care 11:247–257CrossRef Hart NH, Galvão DA, Newton RU (2017) Exercise medicine for advanced prostate cancer. Cur Opin Support Palliat Care 11:247–257CrossRef
5.
Zurück zum Zitat Galvao DA, Taaffe DR, Spry N, Joseph D, Turner D, Newton RU (2008) Reduced muscle strength and functional performance in men with prostate cancer undergoing androgen suppression: a comprehensive cross-sectional investigation. Prostate Cancer Prostatic Dis 12:198–203CrossRefPubMed Galvao DA, Taaffe DR, Spry N, Joseph D, Turner D, Newton RU (2008) Reduced muscle strength and functional performance in men with prostate cancer undergoing androgen suppression: a comprehensive cross-sectional investigation. Prostate Cancer Prostatic Dis 12:198–203CrossRefPubMed
6.
Zurück zum Zitat Smith MR, Finkelstein JS, McGovern FJ, Zietman AL, Fallon MA, Schoenfeld DA et al (2002) Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab 87:599–603CrossRefPubMed Smith MR, Finkelstein JS, McGovern FJ, Zietman AL, Fallon MA, Schoenfeld DA et al (2002) Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab 87:599–603CrossRefPubMed
7.
Zurück zum Zitat Tzortzis VSM, Zachos I, Oeconomou A, Pisters L, Bargiota A (2017) Adverse effects of androgen deprivation therapy in patients with prostate cancer: focus on metabolic complications. Hormones 16:115–123PubMed Tzortzis VSM, Zachos I, Oeconomou A, Pisters L, Bargiota A (2017) Adverse effects of androgen deprivation therapy in patients with prostate cancer: focus on metabolic complications. Hormones 16:115–123PubMed
8.
Zurück zum Zitat Keating NL, O’Malley AJ, Freedland SJ, Smith MR (2010) Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J Natl Cancer Inst 102:39–46CrossRefPubMedPubMedCentral Keating NL, O’Malley AJ, Freedland SJ, Smith MR (2010) Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J Natl Cancer Inst 102:39–46CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Alibhai SMH, Duong-Hua M, Sutradhar R, Fleshner NE, Warde P, Cheung AM et al (2009) Impact of androgen deprivation therapy on cardiovascular disease and diabetes. J Clinl Oncol 27:3452–3458CrossRef Alibhai SMH, Duong-Hua M, Sutradhar R, Fleshner NE, Warde P, Cheung AM et al (2009) Impact of androgen deprivation therapy on cardiovascular disease and diabetes. J Clinl Oncol 27:3452–3458CrossRef
10.
Zurück zum Zitat Kim HS, Moreira DM, Smith MR, Presti JC Jr, Aronson WJ, Terris MK et al (2011) A natural history of weight change in men with prostate cancer on androgen-deprivation therapy (ADT): results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int 107:924–928CrossRefPubMed Kim HS, Moreira DM, Smith MR, Presti JC Jr, Aronson WJ, Terris MK et al (2011) A natural history of weight change in men with prostate cancer on androgen-deprivation therapy (ADT): results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int 107:924–928CrossRefPubMed
11.
Zurück zum Zitat Braunstein LZ, Chen M-H, Loffredo M, Kantoff PW, D’Amico AV (2014) Obesity and the odds of weight gain following androgen deprivation therapy for prostate cancer. Prostate Cancer 2014:230812CrossRefPubMedPubMedCentral Braunstein LZ, Chen M-H, Loffredo M, Kantoff PW, D’Amico AV (2014) Obesity and the odds of weight gain following androgen deprivation therapy for prostate cancer. Prostate Cancer 2014:230812CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Keto CJ, Aronson WJ, Terris MK, Presti JC, Kane CJ, Amling CL et al (2012) Obesity is associated with castration-resistant disease and metastasis in men treated with androgen deprivation therapy after radical prostatectomy: results from the SEARCH database. BJU Int 110:492–498CrossRefPubMed Keto CJ, Aronson WJ, Terris MK, Presti JC, Kane CJ, Amling CL et al (2012) Obesity is associated with castration-resistant disease and metastasis in men treated with androgen deprivation therapy after radical prostatectomy: results from the SEARCH database. BJU Int 110:492–498CrossRefPubMed
13.
Zurück zum Zitat Freedland SJ, Vidal AC, Howard LE, Terris MK, Cooperberg MR, Amling CL et al (2017) Race and risk of metastases and survival after radical prostatectomy: results from the SEARCH database. Cancer 123:4199–4206CrossRefPubMedPubMedCentral Freedland SJ, Vidal AC, Howard LE, Terris MK, Cooperberg MR, Amling CL et al (2017) Race and risk of metastases and survival after radical prostatectomy: results from the SEARCH database. Cancer 123:4199–4206CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Vidal AC, Howard LE, Sun SX, Cooperberg MR, Kane CJ, Aronson WJ et al (2017) Obesity and prostate cancer-specific mortality after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Prostate Cancer Prostatic Dis 20:72–78CrossRefPubMed Vidal AC, Howard LE, Sun SX, Cooperberg MR, Kane CJ, Aronson WJ et al (2017) Obesity and prostate cancer-specific mortality after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Prostate Cancer Prostatic Dis 20:72–78CrossRefPubMed
15.
Zurück zum Zitat Rodriguez C, Freedland SJ, Deka A, Jacobs EJ, McCullough ML, Patel AV et al (2007) Body mass index, weight change, and risk of prostate cancer in the cancer prevention study II nutrition cohort. Cancer Epidemiol Biomark Prev 16:63–69CrossRef Rodriguez C, Freedland SJ, Deka A, Jacobs EJ, McCullough ML, Patel AV et al (2007) Body mass index, weight change, and risk of prostate cancer in the cancer prevention study II nutrition cohort. Cancer Epidemiol Biomark Prev 16:63–69CrossRef
16.
Zurück zum Zitat Greenland S, Daniel R, Pearce N (2016) Outcome modelling strategies in epidemiology: traditional methods and basic alternatives. Int J Epidemiol 45:565–575CrossRefPubMedPubMedCentral Greenland S, Daniel R, Pearce N (2016) Outcome modelling strategies in epidemiology: traditional methods and basic alternatives. Int J Epidemiol 45:565–575CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C et al (2016) A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 69:428–435CrossRefPubMed Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C et al (2016) A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 69:428–435CrossRefPubMed
18.
Zurück zum Zitat Allott EH, Masko EM, Freedland SJ (2013) Obesity and prostate cancer: weighing the evidence. Eur Urol 63:800–809CrossRefPubMed Allott EH, Masko EM, Freedland SJ (2013) Obesity and prostate cancer: weighing the evidence. Eur Urol 63:800–809CrossRefPubMed
19.
Zurück zum Zitat Cao Y, Ma J (2011) Body mass index, prostate cancer–specific mortality, and biochemical recurrence: a systematic review and meta-analysis. Cancer Prev Res (Philadelphia) 4:486–501CrossRef Cao Y, Ma J (2011) Body mass index, prostate cancer–specific mortality, and biochemical recurrence: a systematic review and meta-analysis. Cancer Prev Res (Philadelphia) 4:486–501CrossRef
20.
Zurück zum Zitat Guerrios-Rivera L, Howard L, Frank J, De Hoedt A, Beverly D, Grant DJ et al (2017) Is body mass index the best adiposity measure for prostate cancer risk? Results from a Veterans Affairs biopsy cohort. Urology 105:129–135CrossRefPubMedPubMedCentral Guerrios-Rivera L, Howard L, Frank J, De Hoedt A, Beverly D, Grant DJ et al (2017) Is body mass index the best adiposity measure for prostate cancer risk? Results from a Veterans Affairs biopsy cohort. Urology 105:129–135CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Isbarn H, Boccon-Gibod L, Carroll PR, Montorsi F, Schulman C, Smith MR et al. Androgen deprivation therapy for the treatment of prostate cancer: consider both benefits and risks. Eur Urol 55:62–75 Isbarn H, Boccon-Gibod L, Carroll PR, Montorsi F, Schulman C, Smith MR et al. Androgen deprivation therapy for the treatment of prostate cancer: consider both benefits and risks. Eur Urol 55:62–75
22.
Zurück zum Zitat Seible DM, Gu X, Hyatt AS, Beard CJ, Choueiri TK, Efstathiou JA et al (2014) Weight gain on androgen deprivation therapy: which patients are at highest risk? Urology 83:1316–1321CrossRefPubMed Seible DM, Gu X, Hyatt AS, Beard CJ, Choueiri TK, Efstathiou JA et al (2014) Weight gain on androgen deprivation therapy: which patients are at highest risk? Urology 83:1316–1321CrossRefPubMed
23.
Zurück zum Zitat Buttigliero C, Vana F, Bertaglia V, Vignani F, Fiori C, Osella G et al (2015) The fat body mass increase after adjuvant androgen deprivation therapy is predictive of prostate cancer outcome. Endocrine 50:223–230CrossRefPubMed Buttigliero C, Vana F, Bertaglia V, Vignani F, Fiori C, Osella G et al (2015) The fat body mass increase after adjuvant androgen deprivation therapy is predictive of prostate cancer outcome. Endocrine 50:223–230CrossRefPubMed
24.
Zurück zum Zitat Dickerman BA, Ahearn TU, Giovannucci E, Stampfer MJ, Nguyen PL, Mucci LA et al (2017) Weight change, obesity and risk of prostate cancer progression among men with clinically localized prostate cancer. Int J Cancer 141:933–944CrossRefPubMedPubMedCentral Dickerman BA, Ahearn TU, Giovannucci E, Stampfer MJ, Nguyen PL, Mucci LA et al (2017) Weight change, obesity and risk of prostate cancer progression among men with clinically localized prostate cancer. Int J Cancer 141:933–944CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Cheung AS, Hoermann R, Dupuis P, Joon DL, Zajac JD, Grossmann M (2016) Relationships between insulin resistance and frailty with body composition and testosterone in men undergoing androgen deprivation therapy for prostate cancer. Euro J Endocrinol 175:229–237CrossRef Cheung AS, Hoermann R, Dupuis P, Joon DL, Zajac JD, Grossmann M (2016) Relationships between insulin resistance and frailty with body composition and testosterone in men undergoing androgen deprivation therapy for prostate cancer. Euro J Endocrinol 175:229–237CrossRef
26.
Zurück zum Zitat Kiwata JL, Dorff TB, Schroeder ET, Gross ME, Dieli-Conwright CM (2016) A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients. Prostate Cancer Prostatic Dis 19:323–332CrossRefPubMedPubMedCentral Kiwata JL, Dorff TB, Schroeder ET, Gross ME, Dieli-Conwright CM (2016) A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients. Prostate Cancer Prostatic Dis 19:323–332CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat de Rooy C, Grossmann M, Zajac JD, Cheung AS (2016) Targeting muscle signaling pathways to minimize adverse effects of androgen deprivation. Endocr Relat Cancer 23:R15–R26CrossRefPubMed de Rooy C, Grossmann M, Zajac JD, Cheung AS (2016) Targeting muscle signaling pathways to minimize adverse effects of androgen deprivation. Endocr Relat Cancer 23:R15–R26CrossRefPubMed
28.
Zurück zum Zitat Warburton DER, Gledhill N, Quinney A (2001) The effects of changes in musculoskeletal fitness on health. Can J Appl Physiol 26:161–216CrossRefPubMed Warburton DER, Gledhill N, Quinney A (2001) The effects of changes in musculoskeletal fitness on health. Can J Appl Physiol 26:161–216CrossRefPubMed
29.
Zurück zum Zitat Alibhai SMH, Breunis H, Timilshina N, Naglie G, Tannock I, Krahn M et al (2015) Long-term impact of androgen-deprivation therapy on physical function and quality of life. Cancer 121:2350–2357CrossRefPubMed Alibhai SMH, Breunis H, Timilshina N, Naglie G, Tannock I, Krahn M et al (2015) Long-term impact of androgen-deprivation therapy on physical function and quality of life. Cancer 121:2350–2357CrossRefPubMed
30.
Zurück zum Zitat Bourke L, Doll H, Crank H, Daley A, Rosario D, Saxton JM (2011) Lifestyle intervention in men with advanced prostate cancer receiving androgen suppression therapy: a feasibility study. Cancer Epidemiol Biomark Prev 20:647–657CrossRef Bourke L, Doll H, Crank H, Daley A, Rosario D, Saxton JM (2011) Lifestyle intervention in men with advanced prostate cancer receiving androgen suppression therapy: a feasibility study. Cancer Epidemiol Biomark Prev 20:647–657CrossRef
31.
Zurück zum Zitat Segal RJ, Reid RD, Courneya KS, Malone SC, Parliament MB, Scott CG et al (2003) Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol 21:1653–1659CrossRefPubMed Segal RJ, Reid RD, Courneya KS, Malone SC, Parliament MB, Scott CG et al (2003) Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol 21:1653–1659CrossRefPubMed
32.
Zurück zum Zitat Owen PJ, Daly RM, Livingston PM, Fraser SF (2017) Lifestyle guidelines for managing adverse effects on bone health and body composition in men treated with androgen deprivation therapy for prostate cancer: an update. Prostate Cancer Prostatic Dis 20:137–145CrossRefPubMedPubMedCentral Owen PJ, Daly RM, Livingston PM, Fraser SF (2017) Lifestyle guidelines for managing adverse effects on bone health and body composition in men treated with androgen deprivation therapy for prostate cancer: an update. Prostate Cancer Prostatic Dis 20:137–145CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Volek JS, Volk BM, Gomez AL, Kunces LJ, Kupchak BR, Freidenreich DJ et al (2013) Whey protein supplementation during resistance training augments lean body mass. J Am Coll Nutr 32:122–135CrossRefPubMed Volek JS, Volk BM, Gomez AL, Kunces LJ, Kupchak BR, Freidenreich DJ et al (2013) Whey protein supplementation during resistance training augments lean body mass. J Am Coll Nutr 32:122–135CrossRefPubMed
34.
Zurück zum Zitat Freedland S, Aronson W, Howard L, Smith J, Smith M, Stout J et al (2016) A prospective randomized trial of dietary carbohydrate restriction for men initiating androgen deprivation therapy: carbohydrate and prostate study I (CAPS1). J Urol 195:e29–e30CrossRef Freedland S, Aronson W, Howard L, Smith J, Smith M, Stout J et al (2016) A prospective randomized trial of dietary carbohydrate restriction for men initiating androgen deprivation therapy: carbohydrate and prostate study I (CAPS1). J Urol 195:e29–e30CrossRef
Metadaten
Titel
First-year weight loss with androgen-deprivation therapy increases risks of prostate cancer progression and prostate cancer-specific mortality: results from SEARCH
verfasst von
Kagan Griffin
Ilona Csizmadi
Lauren E. Howard
Gina-Maria Pomann
William J. Aronson
Christopher J. Kane
Christopher L. Amling
Matthew R. Cooperberg
Martha K. Terris
Jennifer Beebe-Dimmer
Stephen J. Freedland
Publikationsdatum
30.01.2019
Verlag
Springer International Publishing
Erschienen in
Cancer Causes & Control / Ausgabe 3/2019
Print ISSN: 0957-5243
Elektronische ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-019-1133-5

Weitere Artikel der Ausgabe 3/2019

Cancer Causes & Control 3/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.