2018 Congress of the Mexican Association of Oncological Urology

Rationale for Radical Prostatectomy for Non-Castrate Oligometastatic Prostate Cancer

Acapulco, GRO, Mexico (UroToday.com) The incidence of newly diagnosed synchronous M1 prostate cancer has decreased in the modern PSA era from 60 to 20% and the standard treatment for this condition is androgen deprivation therapy (ADT) with or without systemic chemotherapy. The oncological outcomes of ADT are predictably poor and there are several caveats associated with this treatment in this particular setting: 

  • Firstly, overall outcomes of this therapy are inversely related to disease burden. 
  • ADT alone does not eliminate metastatic disease.
  • Systemic therapy alone dose note eradicate the primary tumor.
  • Even in the neo adjuvant setting, prostates removed after up to 8 months of treatment are rarely tumor-free.
Currently there are multiple therapies available for newly diagnosed M1 non-castrate prostate cancer that prolong survival (see figure 1). The natural history of this disease indicates that these patients will probably die from cancer and this leads us to believe that the combination of systemic therapy with local primary tumor control may halt the natural progression of this disease and may be of benefit in selected individuals. 

Figure 1: 
Fig1_ClinicalMetastases_Chart.png
The concept of primary tumor control in combination with effective systemic therapy is not new in oncology and is standard of care in colon cancer, ovarian cancer and renal cell cancer.

Data from the SEER database (2004-2010) suggests a survival benefit for local therapy including radical prostatectomy in men with documented stage IV (M1a-c) prostate cancer at diagnosis (75.8% vs. 48.7% in patients without surgery or radiotherapy). However, he underlines the limitations and selection bias of the SEER data. Similar results were found in a German study of 61 patients where time to castrate-resistant prostate cancer, time to clinical progression and cancer-specific survival was slightly better in patients treated with radical prostatectomy; 40 vs. 29 months, 38.6 vs 26.5 months and 95.6% vs. 84.2%, respectively. 

Patient selection in this setting is of upmost importance. Radical prostatectomy in metastatic disease is not for everyone but certainly may be for some and it is currently an evolving strategy. The concept is based on treating the primary tumor and the metastasis sites as separate diseases with different therapeutic alternatives. An example is the following: offer radical prostatectomy for the primary tumor, with pelvic or retroperitoneal lymph node dissection associated with systemic therapy and radiation therapy to the oligometastastic foci. 

An MSKCC pilot study was conducted to assess the safety and feasibility of radical prostatectomy in highly selected M1 prostate cancer with oligometastastic disease that included 20 patients and found that surgical morbidity was low and functional outcomes were acceptable in this setting. (See figure 2) Oncological outcomes were satisfactory with six patients being able to discontinue ADT without evidence of progression. 

Figure 2: 
Fig2_PatientSelection_Multimodal.png
A phase 2 trial is currently active in MSKCC that combines ipilimumab and degarelix with radical prostatectomy to potentially cure patients with metastatic non-castrate prostate cancer. He highlights that this trial has encountered significant toxicity with this therapy and dose adjustments have been made. There are currently several phase 3 trials (Stampede, PEACE 1 trial, etc.) that are ongoing that will further clarify the role of surgery in this complex setting. 

Presented by: Karim A. Touijer, MD, MPH from the Memorial Sloan Kettering Cancer Center, New York, NY

Written by: Adrián M. Garza-Gangemi, MD, Resident of Urology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico @aggangemi & Dr Ashish M. Kamat, Professor of Urologic Oncology, MD Anderson Cancer Center, Houston, TX at the 2018 Congreso de la Asociación Mexicana de Urología Oncológica – July 25-28, 2018, Acapulco, GRO México
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