EAU 2019: Challenging Paradigms in Advanced Prostate Cancer: A New Era

Barcelona, Spain (UroToday.com) Dr. Maria Ribal from Barcelona started the urogenital cancer treatment at a glance session by giving an overview of challenging paradigms in advanced prostate cancer. Dr. Ribal notes that not only is the incidence of prostate cancer the highest among male malignancies, but there is also expected to be a 188% increase in men >65 years of age during the next few years. Regarding advanced prostate cancer, the incidence of metastatic prostate cancer varies greatly:

  • North America: 3%
  • South America: 4-10%
  • Europe: 6%
  • Asia: 60%
Although the incidence of metastatic prostate cancer is only 3% in North America, there is concern that with decreased PSA screening the incidence of metastatic disease may be increasing1.

Dr. Ribal states that imaging has changed many concepts in advanced prostate cancer. For example, she notes that we have likely treated many patients with locally advanced/localized high-risk patients without knowing that they are oligo M1 disease. She points to a paper by Eiber et al.that assessed 248 patients with biochemical recurrence after radical prostatectomy and the ability of 68Ga-PSMA PET/CT to detect recurrence. The detection rates were 96.8% at PSA ≥2, 93.0% at PSA 1 to <2, 72.7% at PSA 0.5 to <1, and 57.9% for PSA 0.2 to <0.5 ng/mL. Whereas detection rates increased with a higher PSA velocity, no significant association could be found for PSA doubling time.

From 2015-2017, we had a very exciting time period for advanced prostate cancer. First, we had the STAMPEDE3 and CHAARTED4 trials demonstrating that men with de novo metastatic/locally advanced disease had a 22% and 39% decreased risk of death, respectively with the addition of docetaxel to ADT. Subsequently, at the 2017 ASCO annual meeting, STAMPEDE5 and LATITUDE6 reported data from their phase III trials assessing abiraterone + ADT among men with de novo metastatic/locally advanced disease. STAMPEDE demonstrated a 37% decreased risk of death in the abiraterone group, compared to 38% in the LATITUDE trial.

Dr. Ribal notes that we have also seen an upswing in studies evaluating the role of surgery in locally advanced and oligometastatic disease. Among 106 patients in the USA, Germany, Italy, and Sweden with newly diagnosed M1 disease who underwent radical prostatectomy, 79.2% of patients did not suffer any complications7  The positive-margin rate was 53.8%, lymphocele rate was 8.5%, and wound infection rate was 4.7%. At a median follow-up of 22.8 months, 88.7% of men were still alive. In a subsequent study by Sooriakumaren et al.8 , they used a Swedish population-based database to assess outcomes among 630 men undergoing radiation therapy, 120 undergoing radical prostatectomy, and 17,602 patients treated with ADT. Patients treated with initial ADT had a nearly three-fold higher hazard of prostate-cancer death compared with initial radical therapy (HR 2.87, 95%CI 2.16-3.82).

Based on improved imaging, there has also been the adoption of salvage pelvic lymphadenectomy among appropriately selected patients. In a review of the role of salvage lymph node dissection, Heidenreich et al.9 highlighted several important points:
  • Salvage pelvic lymphadenectomy should be included in the therapeutic armamentarium of prostate cancer patients with oligometastatic disease
  • Salvage pelvic lymphadenectomy should always be performed as an extended lymphadenectomy
  • Salvage lymphadenectomy significantly prolongs the median time until systemic treatment
  • Patients with PSA <4 ng/mL, a PSA doubling time more than 1 year, three or less visible lymph nodes, and the absence of retroperitoneal lymph node metastases appear to represent the ideal candidates

As follows is Dr. Ribal’s algorithm for the treatment of advanced prostate cancer:
EAU 2019 Challenging Paradigms
Because of the advances in the treatment of mCRPC, there are now patients treated with first, second, third and even fourth lines of therapy. The Prostate Cancer Clinical Trials Working Group 310, provides the following schematic:

EAU 2019 Challenging Paradigms 1
Finally, we have seen an explosion of data assessing the genomics of advanced disease. In 2014, Antonarakis et al. 11 found that among 31 enzalutamide-treated patients and 31 abiraterone- treated patients, 39% and 19%, respectively, had detectable AR-V7 in circulating tumor cells. Among men receiving enzalutamide or abiraterone, AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients and shorter PSA progression-free survival, clinical or radiographic progression-free survival, and overall survival. Furthermore, among 204 patients with mCRPC, TMPRSS2-ERG expression was correlated with PSA-progression-free survival, radiological-progression-free survival, and OS12

Dr. Ribal concluded this high-level overview of advanced prostate cancer by reminding everyone that we must have patient-centered care based on Picker’s Eight Principles:

Picker's Eight Principles of Patient-Centered Care
  • Respect for patients' preferences
  • Coordination and integration of care
  • Information and education
  • Physical comfort
  • Emotional support
  • Involvement of family and friends
  • Continuity and transition
  • Access to care


Presented by: Maria J. Ribal, MD, Hospital Clinic, Caparros, Barcelona, Spain

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia Twitter: @zklaassen_md at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.

References:

  1. Dalela D, Sun M, Diaz M, et al. Contemporary trends in the incidence of metastatic prostate cancer among US men: Results from Nationwide Analyses. Eur Urol Focus 2019 Jan;5(1):77-80.
  2. Eiber M, Maurer T, Souvatzoglou M, et al. Evaluation of Hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med 2015 May;56(5):668-674.
  3. James ND, Sydes MR, Clarke NW, et al. 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. Lancet. 2016;387(10024):1163-1177.
  4. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746.
  5. James ND, de Bono JS, Spears MR, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017;377(4):338-351.
  6. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352-360.
  7. 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 May;69(5):788-794.
  8. Sooriakumaran P, Nyberg T, Akre O, et al. Survival among men at high risk of disseminated prostate cancer receiving initial locally directed radical treatment or initial androgen deprivation therapy. Eur Urol 2017;72(3):345-351.
  9. Heidenreich A, Moul JW, Shariat S, et al. Role of salvage lymph node dissection in prostate cancer. Curr Opin Urol 2016 Nov;26(6):581-589.
  10. Scher HI, Morris MJ, Stadler WM, et al. Trial design and objectives for castration-resistant prostate cancer: Updated recommendations from the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol 2016 Apr 20;34(12):1402-1418.
  11. Antonarakis ES, Lu C, Wang H, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 2014 Sep 11;371(11):1028-1038.
  12. Marin-Aguilera M, Reig O, Mila-Guasch M, et al. The influence of treatment sequence in the prognostic value of TMPRSS2-ERG as biomarker of taxane resistance in castration-resistant prostate cancer. Int J Cancer. 2019 Feb 26 [Epub ahead of print].

 

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