SIU 2019: Chemotherapy and ARATs vs Metastases-Directed Therapy for mHSPC

Athens, Greece (UroToday.com) Markus Graefen, MD, gave an overview of the role of experimental metastases directed therapies in the era of proven life-prolonging drugs and radiation to the primary tumor in the setting of metastatic hormone-sensitive prostate cancer (mHSPC).

Currently, the standard treatment of mHSPC includes androgen deprivation therapy (ADT) and either docetaxel or androgen receptor-axis-targeted therapies (ARAT). Furthermore, radiotherapy to the primary tumor in this setting with a low metastatic burden has been prospectively proven to be effective. The role of metastases-directed therapies (MDT) is still regarded as experimental.

There are many therapeutic options for mHSPC nowadays, as can be seen in Figure 1. The systemic treatments available in mHSPC stratified by disease burden can be seen in Figure 2.

Figure 1 – Potential therapeutic option in metastatic hormone-sensitive prostate cancer:

Figure 2 – Systemic treatment options in metastatic hormone-sensitive prostate cancer:

Next, Dr. Graefen moved on to discuss the evidence available on the treatment of the primary tumor in the setting of mHSPC. The STAMPEDE study¹ has shown an overall survival benefit when radiating the prostate in mHSPC patients with low metastatic burden disease  (Figure 3). This has resulted in the guidelines to now recommend radiotherapy to the prostate in patients presenting with metastatic disease according to the CHAARTED criteria.²

Figure 3 – Overall survival in low and high metastatic burden disease when radiating the prostate in the STAMPEDE trial¹:

The rationale for MDT with radiotherapy to the prostate in oligometastatic disease include:

1. Prevention of local complications (pain, fracture, and others)
2. Deferral of systemic treatment
3. Prevention of development of additional metastases
4. Destruction of cells prone to genetic instability

There are retrospective data showing that performing radical prostatectomy instead of radiotherapy to the prostate in mHSPC patients with low metastatic burden disease has comparable results³ (Table 1). However, these are retrospective data, and therefore there are currently several ongoing prospective randomized trials assessing local therapy in the form of surgery and radiotherapy in mHSPC patients (Table 2).

Table 1 – Comparison of radical prostatectomy to radiotherapy to the prostate in mHSPC patients with low metastatic burden disease: 

Table 2 – Ongoing randomized trials assessing the role of local therapy in mHSPC patients:

 Summarizing his talk, Dr. Graefen reiterated that the standard treatment of mHSPC patients to date is ADT + docetaxel or ARAT. Additionally, radiotherapy to the primary tumor is recommended in patients with low metastatic burden disease. MDT is still regarded as an experimental therapy until we have more level one prospective evidence on its utility.

References:

1. 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.
2. 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.
3. Knipper S, Beyer B, Mandel P, et al. Outcome of patients with newly diagnosed prostate cancer with low metastatic burden treated with radical prostatectomy: a comparison to STAMPEDE arm H. World journal of urology 2019.

Presented by: Markus Graefen, MD, University Medical Center Hamburg-Eppendorf, Germany

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