Getting better at treating prostate cancer: what clinicians should want from scientists

Abstract

If the treatment landscape for prostate cancer is to be transformed, clinicians and scientists must work together ever more closely. Prostate cancer defeats physicians when patients are not accurately stratified according to patients’ risk of dying of disease, when the effects of tumor heterogeneity are insufficiently understood, and when attempts at therapy by clinicians spur further disease evolution and the emergence of new resistance mechanisms. At the same time, clinicians’ over-treat men who in reality do not need it, and some of those men needlessly suffer long term side effects as a result. This commentary is aimed at stimulating debate about how we as clinicians and scientists can assist one another and improve our knowledge to the benefit of patients dying from metastatic disease.

Keywords

Prostate cancer / metastasis / androgen deprivation therapy / abiraterone STAMPEDE trial / LATTITUDE trial

References

[1] Montie JE.Whitmoreisms: memorable quotes from Willet F. Whitmore, Jr, M.D..Urology2004;63:207-9

[2] James ND,Clarke NW,Dearnaley DP,Ritchie AW,Russell JM,de Bono J,Jones RJ,Amos C,Millman R,Beesley S,Brock S,Chakraborti P,Cook A,Gale J,Graham JD,Hughes R,McKinna F,O'Sullivan JM,Peedell C,Robinson AJ,Srinivasan R,Sundar S,Tsang D,Parmar MK.Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial..Lancet2016;387:1163-77

[3] Edwards BK,Mariotto AB,Boscoe FP,Jemal A,Anderson RN,Eheman CR.Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer..Cancer2014;120:1290-314 PMCID:PMC3999205

[4] EAU-ESTRO-ESUR-SIOG Prostate Cancer Guidelines Panel..Prostate cancer and the John West effect..Eur Urol2017;72:7-9

[5] Hamdy FC,Lane JA,Metcalfe C,Davis M,Turner EL,Oxley J,Staffurth J,Bollina P,Doble A,Gillatt D,Kynaston H,Powell P,Rosario DJ,Neal DE.10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer..N Engl J Med2016;375:1415-24

[6] Donovan JL,Lane JA,Metcalfe C,Blazeby JM,Holding P,Lennon T,Cooper D,Howson J,Lyons N,Thompson P,Blaikie J,Bollina P,Doble A,Gillatt D,Kynaston H,Powell P,Rosario DJ,Davis M,Martin RM.Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer..N Engl J Med2016;375:1425-37 PMCID:PMC5134995

[7] Lane JA,Davis M,Dedman D,Turner EL,Metcalfe C,Martin RM,Hamdy FC.Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial..Lancet Oncol2014;15:1109-18

[8] Bolla M,Warde P,Mirimanoff RO,Bernier J,Sternberg C,Torecilla JL,Cutajar CL,Collette L.External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study..Lancet Oncol2010;11:1066-73

[9] Widmark A,Solberg A,Angelsen A,Lund JA,Hoyer M,Fosså SD.Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial..Lancet2009;373:301-8

[10] Mason MD,Sydes MR,Kirkbride P,Cowan R,Anderson J,Parmar MK,Jovic G,Hetherington J,Barber JB,El-Sharkawi S,Hardman PD,Warde P.Final report of the intergroup randomized study of combined androgen-deprivation therapy plus radiotherapy versus androgen-deprivation therapy alone in locally advanced prostate cancer..J Clin Oncol2015;33:2143-50 PMCID:PMC4477786

[11] Bill-Axelson A,Garmo H,Taari K,Nordling S,Andersson SO,Andren O,Steineck G,Johansson JE.Radical prostatectomy or watchful waiting in early prostate cancer..N Engl J Med2014;370:932-42 PMCID:PMC4118145

[12] Wilt TJ,Jones KM,Aronson WJ,Gingrich JR,Gilhooly P,Nsouli I,Cartagena R,Roehrborn C,Blank W,Andriole GL,Wheeler T.Radical prostatectomy versus observation for localized prostate cancer..N Engl J Med2012;367:203-13 PMCID:PMC3429335

[13] Nelson WG.Commentary on Huggins and Hodges: "Studies on prostatic cancer"..Cancer Res2016;76:186-7

[14] Gundem G,Kremeyer B,Tubio JMC,Brewer DS,Hognas G,Kivinummi K,Latimer C,Dawson KJ,Emmert-Buck MR,Foster C,Easton D,Group IP,Cooper CS,Visakorpi T,McDermott U,Bova GS.The evolutionary history of lethal metastatic prostate cancer..Nature2015;520:353-7 PMCID:PMC4413032

[15] Studer UE,Albrecht W,de Reijke T,Loidl W,Sundaram SK,Collette L.Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891..J Clin Oncol2006;24:1868-76

[16] Studer UE,Wimpissinger F,de Reijke TM,Loidl W,Sundaram SK.Differences in time to disease progression do not predict for cancer-specific survival in patients receiving immediate or deferred androgen-deprivation therapy for prostate cancer: final results of EORTC randomized trial 30891 with 12 years of follow-up..Eur Urol2014;66:829-38

[17] O'Donnell A,Dowsett M,Dearnaley D,Harland S,Halbert G,Jarman M.Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer..Br J Cancer2004;90:2317-25 PMCID:PMC2409523

[18] Mohler JL,Ford OH3rd,Weaver CM,Wilson EM.The androgen axis in recurrent prostate cancer..Clin Cancer Res2004;10:440-8

[19] de Bono JS,Molina A,North S,Chi KN,Goodman OB, Jr,.Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI; COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer..N Engl J Med2011;364:1995-2005 PMCID:PMC3471149

[20] Ryan CJ,Fizazi K,Mulders PF,Miller K,Shore ND,Carles J,Taplin ME,de Souza P,Griffin TW,Yu MK,Li J,Naini V,Rathkopf DE.Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study..Lancet Oncol2015;16:152-60

[21] Beer TM,Rathkopf DE,Sternberg CN,Iversen P,Carles J,Davis ID,Evans CP,Joshua AM,Kimura G,Mansbach H,Noonberg SB,Phung D,Scher HI,Venner PM.Enzalutamide in metastatic prostate cancer before chemotherapy..N Engl J Med2014;371:424-33 PMCID:PMC4418931

[22] Scher HI,Saad F,Sternberg CN,de Wit R,Chi KN,Armstrong AJ,Flechon A,Fleming M,Hirmand M,Seely L.Increased survival with enzalutamide in prostate cancer after chemotherapy..N Engl J Med2012;367:1187-97

[23] Sweeney CJ,Carducci M,Jarrard DF,Wong YN,Kohli M,Dreicer R,Picus J,Hussain M,DiPaola RS.Chemohormonal therapy in metastatic hormone-sensitive prostate cancer..N Engl J Med2015;373:737-46 PMCID:PMC4562797

[24] Galazi M,Ng T,Chowdhury S.Precision medicine for prostate cancer..Expert Rev Anticancer Ther2014;14:1305-15

[25] Packer JR.The molecular and cellular origin of human prostate cancer..Biochim Biophys Acta2016;1863:1238-60