Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Advanced Prostate Cancer Consensus Conference (APCCC) 2015 in St. Gallen

Kritische Betrachtung der Empfehlungen zur Diagnostik und Therapie des metastasierten Prostatakarzinoms durch ein deutsches Expertengremium

Advanced Prostate Cancer Consensus Conference (APCCC) 2015 in St. Gallen

Critical review of the recommendations on diagnosis and therapy of metastatic prostate cancer by a German expert panel

Zusammenfassung

Im März 2015 fand erstmalig die Advanced Prostate Cancer Consensus Conference (APCCC) in St. Gallen statt. Kontroversen rund um das fortgeschrittene Prostatakarzinom wurden von 41 Experten aus 17 Ländern diskutiert mit dem Ziel, Konsensusempfehlungen auszusprechen. Die Ergebnisse wurden aktuell in der Fachzeitschrift „Annals of Oncology“ publiziert. Obwohl ein Großteil der in St. Gallen ausgesprochenen Empfehlungen nachvollziehbar ist, sind einige Stellungnahmen kritisch zu betrachten. Als deutsches Expertengremium nehmen wir hierzu Stellung. Im hormonnaiven metastasierten Stadium sollte die kontinuierliche Androgendeprivation (ADT) als Standard gesehen werden. Für eine Überlegenheit der primär maximalen Androgenblockade gibt es keine Evidenz. Nach aktueller Datenlage sollte Patienten mit gutem Allgemeinzustand, insbesondere bei hoher Tumorlast, eine Kombinationstherapie aus ADT plus Taxanen angeboten werden. Im metastasierten kastrationsresistenten Stadium ist als Erstlinientherapie eine Hormonmanipulation mit neuartigen endokrinen Medikamenten Therapie der Wahl in der Mehrheit der Patienten. Taxane haben eine primäre Indikation bei ungünstigen Prognoseparametern. Radium-223 ist eine Option bei ossärer Metastasierung. Von einer nochmaligen Hormonmanipulation nach Versagen von Abirateron oder Enzalutamid in der Erstlinie sollte wenn möglich Abstand genommen werden. Bei Patienten mit gutem Allgemeinzustand sollte Cabazitaxel einen festen Stellenwert in der Sequenztherapie haben. Für das initiale Staging im kastrationsresistenten Stadium ist ein CT-Abdomen/-Thorax plus Knochenszintigramm empfehlenswert. Eine erneute Bildgebung empfiehlt sich bei Tumorprogress, ansonsten alle 4–6 Monate. Bezüglich der Biomarker sollte eine Bestimmung von Serum-PSA und AP alle 2–4 Monate erfolgen.

Abstract

In March 2015, the first Advanced Prostate Cancer Consensus Conference (APCC) took place in St. Gallen. 41 experts from 17 countries reviewed important areas of controversy in advanced hormone-naive and castration-resistant prostate cancer and gave therapy recommendations. These results have been recently published in “Annals of Oncology”. While most of the recommendations from St. Gallen are comprehensible, some of them need to be further discussed. Therefore, we as a German expert panel will critically debate the St. Gallen recommendations. For metastatic hormone-naive prostate cancer, continuous androgen deprivation remains the standard. There is no evidence for superiority of primary maximal androgen deprivation. Patients suitable for chemotherapy, especially in the presence of high tumour burden, should receive androgen deprivation plus taxanes upfront. In metastatic castration resistant prostate cancer, novel hormonal agents like abiraterone or enzalutamid should be the treatment of choice in the majority of patients. Taxanes should be used first-line in patients with unfavourable prognostic markers. Radium-223 is an option in symptomatic patients with bone metastases. There is first evidence that second-line hormonal treatment after first-line failure of a novel endocrine agent has a high failure rate. Cabazitaxel should be part of the treatment sequence in patients with a good performance status. Baseline staging for castration-resistant prostate cancer should include CT-abdomen/-chest and bone scan. Radiographic monitoring should be performed 2 to 3 times a year. Determination of PSA and ALP is to take place every 2 to 4 months.

This is a preview of subscription content, log in to check access.

Literatur

  1. 1.

    Gillessen S, Omlin A, Attard G et al (2015) Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015. Ann Oncol 26:1589–1604

  2. 2.

    Hussain M, Tangen CM, Berry DL et al (2013) Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med 368:1314–1325

  3. 3.

    Crook JM, O’Callaghan CJ, Duncal G et al (2012) Intermittent androgen supression for rising PSA level after radiotherapy. N Engl J Med 367:895–903

  4. 4.

    Prostate Cancer Trialists’ Collaborative Group (2000) Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet 355:1491–1498

  5. 5.

    Samson DJ, Seidenfeld J, Schmitt B et al (2002) Systematic review and meta-analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma. Cancer 95:361–376

  6. 6.

    Caubet JF, Tosteson TD, Dong EW et al (1997) Maximum androgen blockade in advanced prostate cancer: a meta-analysis of published randomized controlled trials using nonsteroidal antiandrogens. Urology 49:71–78

  7. 7.

    Collette L, Studer UE, Schröder FH et al (2001) Why phase III trials of maximal androgen blockade versus castration in M1 prostate cancer rarely show statistically significant differences. Prostate 48(1):29–39

  8. 8.

    Akaza H, Hinotsu S, Usami M et al (2009) Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer 115:3437–3445

  9. 9.

    Gravis G, Fizazi K, Joly F et al (2013) Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol 14(1):49–58

  10. 10.

    Sweeney CJ, Chen YH, Carducci M et al (2015) Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 373(8):737–746

  11. 11.

    Gravis G (2015) Androgen deprivation therapy (ADT) plus docetaxel (D) versus ADT alone for hormone-naive metastatic prostate cancer (PCa): long-term analysis of the GETUG-AFU 15 phase III trial. J Clin Oncol 33(suppl 7): (abstr 140)

  12. 12.

    James ND (2015) Docetaxel and/or zoledronic acid for hormone-naïve prostate cancer: first overall survival results from STAMPEDE (NCT00268476). J Clin Oncol 33(suppl): (abstr 5001)

  13. 13.

    Saad F, Gleason DM, Murray R et al (2002) A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 94:1458–1468

  14. 14.

    Fizazi K, Carducci M, Smith M et al (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 37:813–822

  15. 15.

    Smith MR, Halabi S, Ryan CJ et al (2014) Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance). J Clin Oncol 32:1143–1150

  16. 16.

    Smith MR, Halabi S, Ryan CJ et al (2014) Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance). J Clin Oncol 32:1143–1151

  17. 17.

    Ruggiero SL, Dodson TB, Fantasia J et al (2014) American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw – 2014 update. J Oral Maxillofac Surg 72:1938–1956

  18. 18.

    Smith MR, Saad F, Oudard S et al (2013) Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time. J Clin Oncol 31:3800–3806

  19. 19.

    Lodde M, Lacombe L, Fradet Y (2010) Salvage therapy with bicalutamide 150 mg in nonmetastatic castration-resistant prostate cancer. Urology 76:1189–1193

  20. 20.

    Venkitaraman R, Lorente D, Murthy V et al (2015) A randomised phase 2 trial of dexamethasone versus prednisolone in castration-resistant prostate cancer. Eur Urol 67:673–679

  21. 21.

    Ryan CJ, Smith MR, de Bono JS et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138–148

  22. 22.

    Beer TM, Armstrong AJ, Rathkopf DE et al (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371:424–433

  23. 23.

    Tannock IF, de Wit R, Berry WR et al (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502–1512

  24. 24.

    Berthold DR, Pond GR, Soban F et al (2008) Docetaxel plus prednison or mitoxantrone plus prednison for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 26:242–245

  25. 25.

    Huillard O et al (2013) Efficacy of docetaxel chemotherapy in metastatic prostate cancer (mPC) patients (pts) experiencing early castration resistance (CR). J Clin Oncol 31(suppl): (abstr 5075)

  26. 26.

    van Soest RJ, de Morrée ES, Shen L, Tannock IF, Eisenberger MA, de Wit R (2014) Initial biopsy Gleason score as a predictive marker for survival benefit in patients with castration-resistant prostate cancer treated with docetaxel: data from the TAX327 study. Eur Urol 66:330–336

  27. 27.

    Parker C, Nilsson S, Heinrich D et al (2013) Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 369:213–223

  28. 28.

    Evans C (2014) The prevail study. Primary and non-visceral/visceral disease subgroup results for enzalutamide-treated men with metastatic prostate cancer (MPC) that had progressed on ADT. J Urol 191(4):e223–e224

  29. 29.

    de Bono JS, Oudard S, Ozguroglu M et al (2010) Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376:1147–1154

  30. 30.

    Antonarakis ES, Lu C, Wang H et al (2014) AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 371:1028–1038

  31. 31.

    Azad AA, Volik SV, Wyatt AW et al (2015) Androgen receptor gene aberrations in circulating cell-free DNA: biomarkers of therapeutic resistance in castration-resistant prostate cancer. Clin Cancer Res 21:2315–2324

  32. 32.

    Antonarakis ES, Lu C, Luber B et al (2015) Androgen receptor splice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer. JAMA Oncol 1:582–591

  33. 33.

    Zhang T, Dhawan MS, Healy P et al (2015) Exploring the clinical benefit of docetaxel or enzalutamide after disease progression during abiraterone acetate and prednisone treatment in men with metastatic castration-resistant prostate cancer. Clin Genitourin Cancer 13:392–399

  34. 34.

    Azad AA, Eigl BJ, Murray RN, Kollmannsberger C, Chi KN (2015) Efficacy of enzalutamide following abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer patients. Eur Urol 67:23–29

  35. 35.

    Suzman DL, Luber B, Schweizer MT, Nadal R, Antonarakis ES (2014) Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone. Prostate 74:1278–1285

  36. 36.

    Saad F (2015) Response to taxane chemotherapy as first subsequent therapy after abiraterone acetate in patients with metastatic castration-resistant prostate cancer (mCRPC): post hoc analysis of COU-AA-302. Eur Urol 14:e668–e668a

  37. 37.

    Maines F, Caffo O, Veccia A et al (2015) Sequencing new agents after docetaxel in patients with metastatic castration-resistant prostate cancer. Crit Rev Oncol Hematol 96(3):498–506. doi:10.1016/j.critrevonc.2015.07.013.

  38. 38.

    Heidenreich A, Scholz HJ, Rogenhofer S et al (2013) Cabazitaxel plus prednisone for metastatic castration-resistant prostate cancer progressing after docetaxel: results from the German compassionate-use programme. Eur Urol 63:977–982

  39. 39.

    Heidenreich A, Bracarda S, Manson M et al (2014) Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer: results of the European compassionate-use programme. Eur J Cancer 50:1090–1099

  40. 40.

    Scher HI, Halabi S, Tannock I et al (2008) 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 26:1148–1159

  41. 41.

    NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer. Version I.2015. NCCN.org

  42. 42.

    Morris MJ, Molina A, Small EJ et al (2015) Radiographic progression-free survival as a response biomarker in metastatic castration-resistant prostate cancer: COU-AA-302 results. J Clin Oncol 33:1356–1363

  43. 43.

    Templeton AJ, Pezaro C, Omlin A et al (2014) Simple prognostic score for metastatic castration-resistant prostate cancer with incorporation of neutrophil-to-lymphocyte ratio. Cancer 120:3346–3352

  44. 44.

    Petrelli F, Cabiddu M, Coinu A et al (2015) Prognostic role of lactate dehydrogenase in solid tumors: a systematic review and meta-analysis of 76 studies. Acta Oncol 54:961–970

Download references

Author information

Correspondence to PD Dr. C. Thomas.

Ethics declarations

Interessenkonflikt

C. Thomas, M. Bögemann, F. König, S. Machtens, M. Schostak, T. Steuber und A. Heidenreich geben an, dass kein Interessenkonflikt besteht.

Das Positionspapier basiert auf einem Expertenmeeting, das von der Firma Sanofi finanziert und organisiert wurde. Die Firma hatte keinen Einfluss auf die Inhalte des Manuskriptes.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Thomas, C., Bögemann, M., König, F. et al. Advanced Prostate Cancer Consensus Conference (APCCC) 2015 in St. Gallen . Urologe 55, 772–782 (2016). https://doi.org/10.1007/s00120-016-0030-8

Download citation

Schlüsselwörter

  • APCCC
  • CRPC
  • Metastasiertes Prostatakarzinom
  • Monitoring
  • Therapie

Keywords

  • APCCC
  • CRPC
  • Metastatic prostate cancer
  • Monitoring
  • Treatment