Introduction: We evaluated bone scan index (BSI) as a predictive biomarker for time to castration-resistant prostate cancer (CRPC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Materials and Methods: We identified 85 consecutive mHSPC patients treated with first-line androgen deprivation therapy. We analyzed the correlations between time to CRPC and clinicopathological characteristics, including age, prostate-specific antigen (PSA) level, Gleason score, clinical TNM stage, hemoglobin, lactate dehydrogenase, C-reactive protein, and BSI. Results: The median BSI was 2.7%. Progression to CRPC occurred in 55 (64.7%) patients and the median time to CRPC was 12.9 months. In multivariate analysis, 3 significant risk factors for time to CRPC were identified: age (>73 vs. ≤73 years; hazard ratio [HR] 0.53), p = 0.038, PSA level (>270 vs. ≤270 ng/mL; HR 0.53, p = 0.038), and BSI (>2.7 vs. ≤2.7%; HR 2.97, p < 0.001). Conclusion: Age, PSA level, and BSI were found to be significant predictive factors for time to CRPC in patients with mHSPC.

1.
Oh WK, Kantoff PW: Management of hormone refractory prostate cancer: current standards and future prospects. J Urol 1998;160:1220-1229.
2.
Small EJ, Vogelzang NJ: Second-line hormonal therapy for advanced prostate cancer: a shifting paradigm. J Clin Oncol 1997;15:382-388.
3.
Cooperberg MR, Hinotsu S, Namiki M, Ito K, Broering J, Carroll PR, Akaza H: Risk assessment among prostate cancer patients receiving primary androgen deprivation therapy. J Clin Oncol 2009;27:4306-4313.
4.
Soloway MS, Hardeman SW, Hickey D, Raymond J, Todd B, Soloway S, Moinuddin M: Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer 1988;61:195-202.
5.
Wakabayashi H, Nakajima K, Mizokami A, Namiki M, Inaki A, Taki J, Kinuya S: Bone scintigraphy as a new imaging biomarker: the relationship between bone scan index and bone metabolic markers in prostate cancer patients with bone metastases. Ann Nucl Med 2013;27:802-807.
6.
Uemura K, Miyoshi Y, Kawahara T, Yoneyama S, Hattori Y, Teranishi J, Kondo K, Moriyama M, Takebayashi S, Yokomizo Y, Yao M, Uemura H, Noguchi K: Prognostic value of a computer-aided diagnosis system involving bone scans among men treated with docetaxel for metastatic castration-resistant prostate cancer. BMC Cancer 2016;16:109.
7.
Takahashi Y, Yoshimura M, Suzuki K, Hashimoto T, Hirose H, Uchida K, Inoue S, Koizumi K, Tokuuye K: Assessment of bone scans in advanced prostate carcinoma using fully automated and semi-automated bone scan index methods. Ann Nucl Med 2012;26:586-593.
8.
Poulsen MH, Rasmussen J, Edenbrandt L, Høilund-Carlsen PF, Gerke O, Johansen A, Lund L: Bone Scan Index predicts outcome in patients with metastatic hormone-sensitive prostate cancer. BJU Int 2016;117:748-753.
9.
Nakajima K, Nakajima Y, Horikoshi H, Ueno M, Wakabayashi H, Shiga T, Yoshimura M, Ohtake E, Sugawara Y, Matsuyama H, Edenbrandt L: Enhanced diagnostic accuracy for quantitative bone scan using an artificial neural network system: a Japanese multi-center database project. EJNMMI Res 2013;3:83.
10.
Miyoshi Y, Yoneyama S, Kawahara T, Hattori Y, Teranishi J, Kondo K, Moriyama M, Takebayashi S, Yokomizo Y, Yao M, Uemura H, Noguchi K: Prognostic value of the bone scan index using a computer-aided diagnosis system for bone scans in hormone-naive prostate cancer patients with bone metastases. BMC Cancer 2016;16:128.
11.
Koizumi M, Wagatsuma K, Miyaji N, Murata T, Miwa K, Takiguchi T, Makino T, Koyama M: Evaluation of a computer-assisted diagnosis system, BONENAVI version 2, for bone scintigraphy in cancer patients in a routine clinical setting. Ann Nucl Med 2015;29:138-148.
12.
Kalderstam J, Sadik M, Edenbrandt L, Ohlsson M: Analysis of regional bone scan index measurements for the survival of patients with prostate cancer. BMC Med Imaging 2014;14:24.
13.
Kaboteh R, Damber JE, Gjertsson P, Höglund P, Lomsky M, Ohlsson M, Edenbrandt L: Bone Scan Index: a prognostic imaging biomarker for high-risk prostate cancer patients receiving primary hormonal therapy. EJNMMI Res 2013;3:9.
14.
Kaboteh R, Gjertsson P, Leek H, Lomsky M, Ohlsson M, Sjöstrand K, Edenbrandt L: Progression of bone metastases in patients with prostate cancer - automated detection of new lesions and calculation of bone scan index. EJNMMI Res 2013;3:64.
15.
Imbriaco M, Larson SM, Yeung HW, Mawlawi OR, Erdi Y, Venkatraman ES, Scher HI: A new parameter for measuring metastatic bone involvement by prostate cancer: the Bone Scan Index. Clin Cancer Res 1998;4:1765-1772.
16.
Horikoshi H, Kikuchi A, Onoguchi M, Sjöstrand K, Edenbrandt L: Computer-aided diagnosis system for bone scintigrams from Japanese patients: importance of training database. Ann Nucl Med 2012;26:622-626.
17.
Dennis ER, Jia X, Mezheritskiy IS, Stephenson RD, Schoder H, Fox JJ, Heller G, Scher HI, Larson SM, Morris MJ: Bone scan index: a quantitative treatment response biomarker for castration-resistant metastatic prostate cancer. J Clin Oncol 2012;30:519-524.
18.
Ulmert D, Kaboteh R, Fox JJ, Savage C, Evans MJ, Lilja H, Abrahamsson PA, Björk T, Gerdtsson A, Bjartell A, Gjertsson P, Höglund P, Lomsky M, Ohlsson M, Richter J, Sadik M, Morris MJ, Scher HI, Sjöstrand K, Yu A, Suurküla M, Edenbrandt L, Larson SM: A novel automated platform for quantifying the extent of skeletal tumour involvement in prostate cancer patients using the Bone Scan Index. Eur Urol 2012;62:78-84.
19.
Mitsui Y, Shiina H, Yamamoto Y, Haramoto M, Arichi N, Yasumoto H, Kitagaki H, Igawa M: Prediction of survival benefit using an automated bone scan index in patients with castration-resistant prostate cancer. BJU Int 2012;110:E628-E634.
20.
Armstrong AJ, Kaboteh R, Carducci MA, Damber JE, Stadler WM, Hansen M, Edenbrandt L, Forsberg G, Nordle Ö, Pili R, Morris MJ: Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC). Urol Oncol 2014;32:1308-1316.
21.
Tombal B: Prostate cancer: Bone Scan Index made easy, at last. Nat Rev Urol 2012;9:245-246.
22.
Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL; ISUP Grading Committee: The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 2005;29:1228-1242.
23.
Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M; Prostate Cancer Clinical Trials Working Group: Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 2008;26:1148-1159.
24.
Budczies J, Klauschen F, Sinn BV, Győrffy B, Schmitt WD, Darb-Esfahani S, Denkert C: Cutoff Finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS One 2012;7:e51862.
25.
Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS: Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015;373:737-746.
26.
Miyoshi Y, Noguchi K, Yanagisawa M, Taguri M, Morita S, Ikeda I, Fujinami K, Miura T, Kobayashi K, Uemura H: Nomogram for overall survival of Japanese patients with bone-metastatic prostate cancer. BMC Cancer 2015;15:338.
27.
Smaletz O, Scher HI, Small EJ, Verbel DA, McMillan A, Regan K, Kelly WK, Kattan MW: Nomogram for overall survival of patients with progressive metastatic prostate cancer after castration. J Clin Oncol 2002;20:3972-3982.
28.
Halabi S, Small EJ, Kantoff PW, Kattan MW, Kaplan EB, Dawson NA, Levine EG, Blumenstein BA, Vogelzang NJ: Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J Clin Oncol 2003;21:1232-1237.
29.
Mikkola A, Aro J, Rannikko S, Ruutu M; Finnprostate Group: Prognostic grouping of metastatic prostate cancer using conventional pretreatment prognostic factors. Scand J Urol Nephrol 2009;43:265-270.
30.
Droz JP, Balducci L, Bolla M, Emberton M, Fitzpatrick JM, Joniau S, Kattan MW, Monfardini S, Moul JW, Naeim A, van Poppel H, Saad F, Sternberg CN: Management of prostate cancer in older men: recommendations of a working group of the International Society of Geriatric Oncology. BJU Int 2010;106:462-469.
31.
Iranikhah M, Stricker S, Freeman MK: Future of bisphosphonates and denosumab for men with advanced prostate cancer. Cancer Manag Res 2014;6:217-224.
32.
Dearnaley DP, Mason MD, Parmar MK, Sanders K, Sydes MR: Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: long-term overall survival results from the MRC PR04 and PR05 randomised controlled trials. Lancet Oncol 2009;10:872-876.
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