Management of Non-metastatic castrate-resistant prostate cancer

Panagiotis Mourmouris, Christos Papachristou, Titos Markopoulos, Marinos Mperdempes, Nikolaos Kostakopoulos, Lazaros Lazarou, Mustafa Bilal Tuna, Andreas Skolarikos


When castration resistance is established, it is essential to rule out the presence of metastases or micrometastases by optimizing the use of imaging techniques. If non-metastastic castrate resistant prostate cancer diagnosis is confirmed the physician is in front of a difficult decision: to treat it or not and if not, how he can follow up his patient. In practice, patients awareness of their PSA levels and pressure to act upon any increase of PSA influence management irrespective of physical or radiographic findings. This highlights the need to have more accurate assessment of nmCRPC severity and the risk of progression. We review the literature about this ambiguous entity and we summarize all the available data for it’s management.


prostate Cancer; castrate resistance; androgen deprivation therapy; non metastatic

Full Text:



Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC Natural history of progression after PSA elevation following radical prostatectomy. JAMA 281(17): 1591-1597.

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 294 (4): 433-439.

Antonarakis ES, Feng Z, Trock BJ, Humphreys EB, Carducci MA, Partin AW, Walsh PC, Eisenberger MA Thenatural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term followup. BJU Int 109(1): 32-39.

Moul JW, Wu H, Sun L, McLeod DG, Amling C, Donahue T et al Early versus delayed hormonal therapy for prostate specific antigen only recurrence of prostate cancer after radical prostatectomy. J Urol 171(3): 1141-1147.

Gillessen S, Omlin A, Attard G, de Bono JS, Efstathiou E, Fizazi K et al Management of patients with advanced prostate cancer: recommendations of the St. Gallen Advanced Prostate Cancer Consensus Conference (APCCC). Ann Oncol 26(8): 1589-1604.

Tombal B Non-metastatic CRPC and asymptomatic metastatic CRPC: which treatment for which patient? Ann Oncol 23(Suppl10): x251-x258.

Schulman CC, Irani J, Morote J, Schalken JA, Montorsi F, Chlosta PL et al Testosterone measurement in patients with prostate cancer. Eur Urol 58(1): 65-74.

Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA et al Prostate Cancer Clinical Trials Working G 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 26(7): 1148-1159.

Kirby M, Hirst C, Crawford ED Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 65(11): 1180-119.

Smith MR, Kabbinavar F, Saad F, Hussain A, Gittelman MC, Bilhartz DL et al Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol 23(13): 2918-2925.

Smith MR, Cook R, Lee KA, Nelson JB Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration-resistant nonmetastatic prostate cancer. Cancer 117(10): 2077-2085.

Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B et al Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 379(9810): 39-46.

Van den Bergh L, Lerut E, Haustermans K, Deroose CM, Oyen R et al Final analysis of a prospective trial on functional imaging for nodal staging in patients with prostate cancer at high risk for lymph node involvement. Urol Oncol 33(3): 109e123-109e131.

Tombal B, Lecouvet F (2012) Modern detection of prostate cancer’s bone metastasis: is the bone scan era over? Adv Urol 2012: 893193.

Kitajima K, Murphy RC, Nathan MA, Froemming AT, Hagen CE et al Detection of recurrent prostate cancer after radical prostatectomy: comparison of 11C-choline PET/CT with pelvic multiparametric MR imaging with endorectal coil. J Nucl Med 55(2): 223-232.

Afshar-Oromieh A, Haberkorn U, Schlemmer HP, Fenchel M, Eder M, Eisenhut M et al Comparison of PET/CT and PET/MRI hybrid systems using a 68 Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience. Eur J Nucl Med Mol Imaging 41(5): 887-897.

Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B et al Evaluation of hybrid 68 Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med 56(5): 668-674.

Lecouvet FE, Simon M, Tombal B, Jamart J, Vande Berg BC, et al Whole-body MRI (WB-MRI) versus axial skeleton MRI (AS-MRI) to detect and measure bone metastases in prostate cancer (PCa). Eur Radiol 20(12): 2973-2982.

Pasoglou V, Michoux N, Peeters F, Larbi A, Tombal B et al Whole-body 3D T1-weighted MR Imaging in patients with prostate cancer: feasibility and evaluation in screening for metastatic disease. Radiol 275(1): 155-166.

Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T et al EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014 Feb; 65(2): 467-79.

D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Interval to testosterone recovery after hormonal therapy for prostate cancer and risk of death. Int J Radiat Oncol Biol Phys. 2009 Sep 1; 75(1): 10-5.

Suzuki H, Okihara K, Miyake H, Fujisawa M, Miyoshi S, Matsumoto T et al Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade. J Urol. 2008 Sep; 180(3): 921-7.

Sartor AO, Tangen CM, Hussain MH, Eisenberger MA, Parab M. et al Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426). Cancer. 2008 Jun; 112(11): 2393-400.

Lodde M1, Lacombe L, Fradet Y. Salvage therapy with bicalutamide 150 mg in nonmetastatic castration-resistant prostate cancer Urology. 2010 Nov; 76(5): 1189-93.

Lawrentschuk N, Fernandes K, Bell D, Barkin J, Fleshner N. Efficacy of a second line luteinizing hormone-releasing hormone agonist after advanced prostate cancer biochemical recurrence. J Urol. 2011 Mar; 185(3): 848-54.

Lowrance WT, Roth BJ, Kirkby E, Murad MH, Cookson MS. Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2015. J Urol. 2016 May; 195(5): 1444-52.

Hong JH, Kim IY (2014) Nonmetastatic castration-resistant prostate cancer. Korean J Urol 55(3): 153-160.

Attard G, Reid AH, A’Hern R, Parker C, Oommen NB, Folkerd E et al Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol. 2009 Aug 10;27(23):3742-8

Rathkopf DE, Morris MJ, Fox JJ, Danila DC, Slovin SF, Hager JH, Phase I study of ARN-509, a novel antiandrogen, in the treatment of castration-resistant prostate cancer. J Clin Oncol. 2013 Oct 1;31(28):3525-30.

Hussain M, Corn PG, Michaelson MD, Hammers HJ, Alumkal JJ, Ryan CJ6 et al Phase II study of single-agent orteronel (TAK-700) in patients with nonmetastatic castration-resistant prostate cancer and rising prostate-specific antigen. Clin Cancer Res. 2014 Aug 15;20(16):4218-27. doi: 10.1158/1078-0432.CCR-14-0356. Epub 2014 Jun 25.

Kawalec P, Paszulewicz A, Holko P, Pilc A. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. A systematic review and meta-analysis. Arch Med Sci. 2012 Nov 9;8(5):767-75.

Ogita S, Tejwani S, Heilbrun L Pilot Phase II Trial of Bevacizumab Monotherapy in Nonmetastatic Castrate-Resistant Prostate Cancer. ISRN Oncol. 2012;2012:242850

Crawford ED, Stone NN, Yu EY, Koo PJ, Freedland SJ, Slovin SF Challenges and recommendations for early identification of metastatic disease in prostate cancer. Urology. 2014 Mar;83(3):664-9.