Elevated Alkaline Phosphatase Velocity Strongly Predicts Overall Survival and the Risk of Bone Metastases in Castrate-resistant Prostate Cancer

Overview

Journal Urol Oncol

Publisher Elsevier

Date 2014 Jun 16

PMID 24929891

Citations 21

Authors

Adam R Metwalli

Inger L Rosner

Jennifer Cullen

Yongmei Chen

Timothy Brand

Stephen A Brassell

James LEsperance

Christopher Porter

Joseph Sterbis

David G McLeod

Affiliations

Soon will be listed here.

Abstract

Objectives: In patients with a rising prostate-specific antigen (PSA) level during treatment with androgen deprivation therapy, identification of men who progress to bone metastasis and death remains problematic. Accurate risk stratification models are needed to better predict risk for bone metastasis and death among patients with castration-resistant prostate cancer (CRPC). This study evaluates whether alkaline phosphatase (AP) kinetics predicts bone metastasis and death in patients with CRPC.

Methods And Materials: A retrospective cohort study of 9,547 patients who underwent treatment for prostate cancer was conducted using the Center for Prostate Disease Research Multi-center National Database. From the entire cohort, 347 were found to have CRPC and, of those, 165 had 2 or more AP measurements during follow-up. To determine the AP velocity (APV), the slope of the linear regression line of all AP values was plotted over time. Rapid APV was defined as the uppermost quartile of APV values, which was found to be ≥6.3 IU/l/y. CRPC was defined as 2 consecutive rising PSA values after achieving a PSA nadir<4 ng/ml and documented testosterone values less than 50 ng/dl. The primary study outcomes included bone metastasis-free survival (BMFS) and overall survival (OS).

Results: Rapid APV and PSA doubling time (PSADT) less than 10 months were strong predictors of both BMFS and OS in a multivariable analysis. Faster PSADT was a stronger predictor for BMFS (odds ratio [OR] = 12.1, P<0.0001 vs. OR = 2.7, P = 0.011), whereas rapid APV was a stronger predictor of poorer OS (OR = 5.11, P = 0.0001 vs. OR = 3.98, P = 0.0034). In those with both a rapid APV and a faster PSADT, the odds of developing bone metastasis and death exceeded 50%.

Conclusion: APV is an independent predictor of OS and BMFS in patients with CRPC. APV, in conjunction with PSA-based clinical parameters, may be used to better identify patients with CRPC who are at the highest risk of metastasis and death. These findings need validation in prospective studies.

Citing Articles

Clinical Outcomes and Prognostic Factors in Nonmetastatic Castration-Resistant Prostate Cancer Treated with Androgen Receptor Signaling Inhibitors Therapy.

Fujiwara R, Yamamoto S, Takemura K, Yuasa T, Numao N, Oguchi T Cancers (Basel). 2024; 16(15).

PMID: 39123387 PMC: 11312153. DOI: 10.3390/cancers16152659.

Survival Outcomes by Race and Ethnicity in Veterans With Nonmetastatic Castration-Resistant Prostate Cancer.

Rasmussen K, Patil V, Li C, Yong C, Appukkuttan S, Grossman J JAMA Netw Open. 2023; 6(10):e2337272.

PMID: 37819658 PMC: 10568364. DOI: 10.1001/jamanetworkopen.2023.37272.

Current status of -, -, -heterocycles as potential alkaline phosphatase inhibitors: a medicinal chemistry overview.

Jassas R, Naeem N, Sadiq A, Mehmood R, Alenazi N, Al-Rooqi M RSC Adv. 2023; 13(24):16413-16452.

PMID: 37274413 PMC: 10233329. DOI: 10.1039/d3ra01888a.

Nonmetastatic Castration-Resistant Prostate Cancer: Current Challenges and Trends.

Figueiredo A, Costa L, Mauricio M, Figueira L, Ramos R, Martins-da-Silva C Clin Drug Investig. 2022; 42(8):631-642.

PMID: 35829924 PMC: 9338100. DOI: 10.1007/s40261-022-01178-y.

Development and validation of a multivariable prognostic model in de novo metastatic castrate sensitive prostate cancer.

Roy S, Sun Y, Wallis C, Morgan S, Grimes S, Malone J Prostate Cancer Prostatic Dis. 2022; 26(1):119-125.

PMID: 35790787 DOI: 10.1038/s41391-022-00560-3.

References

Robinson D, Sandblom G, Johansson R, Garmo H, Stattin P, Mommsen S . Prediction of survival of metastatic prostate cancer based on early serial measurements of prostate specific antigen and alkaline phosphatase. J Urol. 2007; 179(1):117-22. DOI: 10.1016/j.juro.2007.08.132. View

Garnero P, Buchs N, Zekri J, Rizzoli R, Coleman R, Delmas P . Markers of bone turnover for the management of patients with bone metastases from prostate cancer. Br J Cancer. 2000; 82(4):858-64. PMC: 2374389. DOI: 10.1054/bjoc.1999.1012. View

Sonpavde G, Pond G, Berry W, de Wit R, Armstrong A, Eisenberger M . Serum alkaline phosphatase changes predict survival independent of PSA changes in men with castration-resistant prostate cancer and bone metastasis receiving chemotherapy. Urol Oncol. 2010; 30(5):607-13. DOI: 10.1016/j.urolonc.2010.07.002. View

Smith M, Saad F, Coleman R, Shore N, Fizazi K, Tombal B . Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2011; 379(9810):39-46. PMC: 3671878. DOI: 10.1016/S0140-6736(11)61226-9. View

Brown J, Cook R, Major P, Lipton A, Saad F, Smith M . Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst. 2005; 97(1):59-69. DOI: 10.1093/jnci/dji002. View

Lein M, Wirth M, Miller K, Eickenberg H, Weissbach L, Schmidt K . Serial markers of bone turnover in men with metastatic prostate cancer treated with zoledronic Acid for detection of bone metastases progression. Eur Urol. 2007; 52(5):1381-7. DOI: 10.1016/j.eururo.2007.02.033. View

Pound C, Partin A, Eisenberger M, Chan D, Pearson J, Walsh P . Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999; 281(17):1591-7. DOI: 10.1001/jama.281.17.1591. View

Ozu C, Nakashima J, Horiguchi Y, Oya M, Ohigashi T, Murai M . Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer. Int J Urol. 2008; 15(5):419-22. DOI: 10.1111/j.1442-2042.2008.02029.x. View

Freedland S, Humphreys E, Mangold L, Eisenberger M, Dorey F, Walsh P . Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005; 294(4):433-9. DOI: 10.1001/jama.294.4.433. View

10.

Brassell S, Dobi A, Petrovics G, Srivastava S, McLeod D . The Center for Prostate Disease Research (CPDR): a multidisciplinary approach to translational research. Urol Oncol. 2009; 27(5):562-9. DOI: 10.1016/j.urolonc.2009.01.023. View

11.

Harris E, Brown S . Temporal changes in the concentrations of serum constituents in healthy men. Distributions of within-person variances and their relevance to the interpretation of differences between successive measurements. Ann Clin Biochem. 1979; 16(4):169-76. DOI: 10.1177/000456327901600142. View

12.

Jung K, Lein M, Stephan C, Von Hosslin K, Semjonow A, Sinha P . Comparison of 10 serum bone turnover markers in prostate carcinoma patients with bone metastatic spread: diagnostic and prognostic implications. Int J Cancer. 2004; 111(5):783-91. DOI: 10.1002/ijc.20314. View

13.

Wilt T, Brawer M, Jones K, Barry M, Aronson W, Fox S . Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012; 367(3):203-13. PMC: 3429335. DOI: 10.1056/NEJMoa1113162. View

14.

Smith M, Cook R, Lee K, Nelson J . Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration-resistant nonmetastatic prostate cancer. Cancer. 2011; 117(10):2077-85. PMC: 3116053. DOI: 10.1002/cncr.25762. View

15.

van Steirteghem A, Robertson E, Young D . Variance components of serum constituents in healthy individuals. Clin Chem. 1978; 24(2):212-22. View

16.

Jung K, Miller K, Wirth M, Albrecht M, Lein M . Bone turnover markers as predictors of mortality risk in prostate cancer patients with bone metastases following treatment with zoledronic acid. Eur Urol. 2010; 59(4):604-12. DOI: 10.1016/j.eururo.2010.12.006. View

17.

Cook R, Coleman R, Brown J, Lipton A, Major P, Hei Y . Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer. Clin Cancer Res. 2006; 12(11 Pt 1):3361-7. DOI: 10.1158/1078-0432.CCR-06-0269. View

18.

Hussain M, Tangen C, Higano C, Schelhammer P, Faulkner J, Crawford E . Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol. 2006; 24(24):3984-90. DOI: 10.1200/JCO.2006.06.4246. View

19.

Mason M, Sydes M, Glaholm J, Langley R, Huddart R, Sokal M . Oral sodium clodronate for nonmetastatic prostate cancer--results of a randomized double-blind placebo-controlled trial: Medical Research Council PR04 (ISRCTN61384873). J Natl Cancer Inst. 2007; 99(10):765-76. DOI: 10.1093/jnci/djk178. View

20.

Smith M, Kabbinavar F, Saad F, Hussain A, Gittelman M, Bilhartz D . Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005; 23(13):2918-25. DOI: 10.1200/JCO.2005.01.529. View