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SIU 2019 39th Annual Society of International Urology Congress

SIU 2019: Debate: Does Radical Prostatectomy Have a Role in the Management of Oligomets? Pro

Athens, Greece (UroToday.com) In this debate, Dr. R. Jeffrey Karnes explained why he believes in the role of radical prostatectomy in the management of oligometastatic prostate cancer.

There are many reasons why it is important to control the primary tumor in oligometastatic disease according to Dr. Karnes:

  1. Diminish symptoms that are caused by the primary tumor
  2. Improve response to systemic therapy as treatment of the primary tumor will lead to a lower mutational load, remove immunosuppression, and will make hormonal therapy more effective against a smaller tumor quantity
  3. Remove the persistent source of future metastases

Next, Dr. Karnes explained the definition of oligometastatic disease. According to the CHAARTED study definition1, the high metastatic burden was defined as four or more bone metastases with one or more outside the vertebral bodies or pelvis, or visceral metastases, or both. Therefore, oligometastatic is defined as anything with a lower disease burden.

The biology of oligometastatic disease is important to understand as well. Primary prostate cancer is multifocal2. Each focus is composed of multiple genetically different cancer cell clones3. However, most, if not all metastatic prostate cancers have monoclonal origins and maintain a unique signature copy number pattern of the parent cancer cell4. Metastasis to metastasis spread has also been found to be common through:

  1. De-novo monoclonal seeding of daughter metastases
  2. Transfer of multiple tumor clones between metastatic sites
  3. Multiple metastases were more closely related to each other than any of them were to the primary tumor
  4. Recent studies using mouse models of cancer demonstrated the existence of polyclonal seeding from and inter-clonal cooperation between multiple subclones.

In a retrospective study done in Mayo clinic between 1966-1995, patients with pTxN+ were matched. A total of 70 patients who underwent orchiectomy alone were matched and compared to 79 patients who underwent orchiectomy and radical prostatectomy. In this study, the 10-year overall survival was considerably higher with patients who underwent both radical prostatectomy and orchiectomy (65% vs. 30%)5. Similar beneficial results for treatment of the primary tumor in the setting of oligometastatic disease have been shown in other centers6, 7. Population-based retrospective cohort studies, for example, have also shown an advantage of treating the primary tumor, both in the SEER database8 and the NCDB database9. Recently, the STAMPEDE trial, a prospective, randomized controlled trial demonstrated an advantage of radiotherapy to the primary tumor in the setting of oligometastatic disease10. Patients with a relatively low tumor risk and good general health will most likely benefit the most, while patients with a predicted overall mortality risk above 70% will not benefit.

Dr. Karnes raised the question of patients with M1a/M1b prostate cancer? In a study assessing 106 such patients with a median follow-up of almost 2 years, enrolling patients between 2007-2014 in several centers, radical prostatectomy was shown to be feasible11. There is also data showing that treating the primary tumor alleviated local symptoms and was associated with longer overall survival12, 13.

Dr. Karnes concluded his talk mentioning some of the ongoing trials assessing the role of surgery in the treatment of the primary tumor in the setting of metastatic disease. These ongoing trials include the TRoMbone study, the g-RAMPP study, the MD-Anderson trial, and SWOG1802 trial.

Dr. Karnes believes that debulking radical prostatectomy in oligometastatic patients should be considered, but we must await the results of randomized trials to make a final decision.

References:

  1. Sweeney CJ, Chen Y-H, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. New England Journal of Medicine 2015; 373(8): 737-46.
  2. Miller GJ, Cygan JM. Morphology of Prostate Cancer: The Effects of Multifocality on Histological Grade, Tumor Volume and Capsule Penetration. Journal of Urology 1994; 152(5 Part 2): 1709-13.
  3. Macintosh CA, Stower M, Reid N, Maitland NJ. Precise microdissection of human prostate cancers reveals genotypic heterogeneity. Cancer research 1998; 58(1): 23-8.
  4. Liu W, Laitinen S, Khan S, et al. Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nature medicine 2009; 15(5): 559-65.
  5. Ghavamian R, Bergstralh EJ, Blute ML, Slezak J, Zincke H. Radical retropubic prostatectomy plus orchiectomy versus orchiectomy alone for pTxN+ prostate cancer: a matched comparison. The Journal of urology 1999; 161(4): 1223-7; discussion 7-8.
  6. Engel J, Bastian PJ, Baur H, et al. Survival benefit of radical prostatectomy in lymph node-positive patients with prostate cancer. Eur Urol 2010; 57(5): 754-61.
  7. Gratzke C, Engel J, Stief CG. Role of radical prostatectomy in metastatic prostate cancer: data from the Munich Cancer Registry. Eur Urol 2014; 66(3): 602-3.
  8. Culp SH, Schellhammer PF, Williams MB. Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study. Eur Urol 2014; 65(6): 1058-66.
  9. Loppenberg B, Dalela D, Karabon P, et al. The Impact of Local Treatment on Overall Survival in Patients with Metastatic Prostate Cancer on Diagnosis: A National Cancer Data Base Analysis. Eur Urol 2017; 72(1): 14-9.
  10. Parker CC, James ND, Brawley CD, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. The Lancet 2018; 392(10162): 2353-66.
  11. Sooriakumaran P, Karnes J, Stief C, et al. A Multi-institutional Analysis of Perioperative Outcomes in 106 Men Who Underwent Radical Prostatectomy for Distant Metastatic Prostate Cancer at Presentation. Eur Urol 2016; 69(5): 788-94.
  12. Patrikidou A, Brureau L, Casenave J, et al. Locoregional symptoms in patients with de novo metastatic prostate cancer: Morbidity, management, and disease outcome. Urologic oncology 2015; 33(5): 202.e9-17.
  13. Poelaert F, Verbaeys C, Rappe B, et al. Cytoreductive Prostatectomy for Metastatic Prostate Cancer: First Lessons Learned From the Multicentric Prospective Local Treatment of Metastatic Prostate Cancer (LoMP) Trial. Urology 2017; 106: 146-52.

Presented by: R. Jeffrey Karnes, MD, Mayo Clinic, Rochester, Minnesota, United States

Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New-York, USA @GoldbergHanan at the 39th Congress of the Société Internationale d'Urologie, SIU 2019, #SIUWorld #SIU2019, October 17-20, 2019, Athens, Greece

Read the Opposing Debate: SIU 2019: Debate: Does Radical Prostatectomy have a Role in the Management of Oligomets? Con