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2018 Friends of Israel Urological Symposium

FOIU 2018: Oncologist View - Local Treatment of Metastatic Prostate Cancer

Tel Aviv, Israel (UroToday.com) Michael Zelefsky, MD, gave a talk about the oncologist’s view on local treatment of metastatic prostate cancer (MPC). The hypothesis that local therapy (LT) could prolong survival in MPC is based on several points. First, tumor cytokine production reaches a critical threshold related to tumor volume and disease burden. Second, increased cytokine production leads to angiogenesis facilitation invasion and metastasis. Third, local therapy could reduce cytokine production and circulating tumor cells. Lastly, LT may reduce further metastasis emanating from the primary tumor.

An analysis of SEER Medicare demonstrated that intensity modulated radiation therapy (IMRT) in MPC patients was associated with a 62% reduction in cause-specific mortality, while surgery was associated with a reduction of 52% in similar patients.1 Another analysis from the national cancer database (NCDB) showed in a multivariable analysis that the following variables are associated with an increase in overall mortality in MPC patients:

  • No local therapy
  • Increased comorbidities
  • Older age
A SEER database study demonstrated that MPC patients undergoing surgery or brachytherapy is associated with a reduction in cause-specific mortality. 5-year disease-free survival outcomes for surgery and brachytherapy were 75% and 62% vs. 48% for those not receiving local therapy.2

Unfortunately, these retrospective population-based studies have serious limitations. Aside from being retrospective, with small numbers comprising the cohorts of the actual locally treated patients, there is a clear selection bias for those getting local therapy. Additionally, there is no information regarding the extent of metastatic disease, and data regarding systemic therapies is not readily available in these series. Lastly, there is no data on the quality of life of the patients receiving local treatment.

In the SPCG-7 trial, the benefit of local therapy with ADT for locally advanced T3N0 disease compared to ADT alone was assessed. This trial demonstrated a survival benefit for local therapy.3 Recently, in the AUA meeting in 2018 in San-Francisco, the HORRAD trial was presented. This is an ongoing phase 3 trial for patients with bone metastases randomized to ADT vs. ADT and local therapy. This is a multicenter trial from the Netherlands, initiated in 2004. The median PSA of the enrolled patients is 142 ng/ml with the primary endpoint being survival, and a median follow-up of up to 4 years. The results so far did not demonstrate any difference in median survival between both arms. It may be difficult to draw conclusions from this cohort, which has a very high burden of metastatic disease, and results may not apply to limited oligometastatic disease. Importantly, patients treated with radiotherapy, only received 70 Gy and the nodes were not treated.

There are additional ongoing prospective trials, addressing in part the role of treating the primary in the setting of metastatic disease. These include:

  • SWOG S1802
  • PEACE – 1: 4 arm trials with 1stgeneration ADT and abiraterone, and also randomizing +/- radiotherapy to the primary tumor
  • TroMbone: ADT + /- radical prostatectomy
In conclusion, Dr. Zelefsky reiterated that retrospective data and large population-based studies suggest that local therapy may provide a cause-specific survival benefit in the setting of metastatic disease. There is no clear evidence at all, that one local therapy is superior to another if it is delivered in an optimal fashion. There are serious limitations to these studies, including their retrospective nature, a small number, limited follow-up, limited information about local treatment, and systemic therapies are given. Lastly, ongoing prospective randomized trials may provide more information regarding the potential benefit of utilizing local therapy in the setting of limited oligometastasis. 


Presented by: Michael J Zelefsky, Memorial Sloan-Kettering Cancer Center, New York, New York, US

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 FOIU 4th Friends of Israel Urological Symposium, July 3-5. 2018, Tel-Aviv, Israel

References:
1. Satkinasivam J Urol 2015
2. Culp et al. Eur Urol 2013
3. Widmark A. et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet 2009