ASCO GU 2018: Debate: Is there Evidence for Local treatment in Patients with Newly Diagnosed Metastatic Disease?

San Francisco, CA ( The management of metastatic prostate cancer has changed dramatically over the last 10 years. Historically the treatment options for patients with metastatic prostate cancer was limited to hormonal therapy. Advances in nuclear medicine techniques have caused a stage migration towards low volume metastatic disease, in many cases oligometastatic disease, raising the questions if local and metastatic directed therapy (MDT) is prudent in this patient population. The debate is started with a case scenario of a 75 yo male presenting with high-risk prostate cancer (PSA:10, Gleason: 9, cT1c) in whom a sodium fluoride PET noted 4 bone metastases. The debaters are asked if local and metastatic directed treatment should be offered or not to this patient.

Dr. Mac Roach, a radiation oncologist from UCSF, advocates for the local and metastases directed treatment in the case presented. Dr. Roach emphasis that while there is no high-level evidence supporting local treatment of disease in the metastatic setting, several population and retrospective reports have pointed towards a likely benefit. In a NCDB study, which assesses the added value of radiation therapy in 6000 patients diagnosed with metastatic disease, patients treated with a combination of ADT+XRT had improved overall (OS) survival compared to those with ADT alone following adjustment for known confounders. Moreover, data inferred from metastatic phase III trials have shown that patients who had primary treatment (XRT) had improved OS compared to those treated with ADT alone. The main limitation of this subtype analyses is the low number of patients who underwent local treatment in the overall trials which often leads to an underpowered association. Local therapy also provides a palliative benefit which is seldom discussed. Patients with newly diagnosed metastatic prostate cancer tend to present with local symptoms which have a significant effect on quality of life (QoL). Dr. Roach presents data on the benefit of SBRT in patients with metastatic prostate cancer presenting with urinary retention. All the patients treated were able to void independently and had decreased episodes of gross hematuria improving their QoL scores. Lastly, Dr. Roach focuses on the benefit of metastases directed therapy (MDT) in patients with oligometastatic disease. A recent small randomized trial (62 patients) by Ost and colleagues, showed that MDT leads to a significantly longer ADT-Free interval compared to those treated with surveillance. Interestingly, QoL scores were similar between both groups and the follow-up has been too short to make in conclusion on the effect of MTD on OS. Data on other disease sites, specifically lung cancer, has shown that MDT has had a significant effect on OS, and the hope is that this benefit in OS will translate to prostate cancer.

Dr. Adam Dicker, a radiation oncologist from Jefferson Hospital, presents the argument against the wide use of local and MDT in this patient population. Dr. Dicker emphasizes that the biology of oligometastatic patients is variable and to date largely unknown. Emerging research in the interplay between metastatic disease and the primary tumor has shown of a possible “malignant” homeostatic state which if interrupted may lead to worsening of metastatic burden. Moreover, there is conflicting evidence of the source of additional metastatic foci, with some arguing the primary tumor as a source, with others showing evidence that metastases give rise to other metastases, so which do we treat! Dr. Dicker shows compelling evidence of how population data, no matter how controlled, can still be significantly biased and lead us to erroneous conclusions. This was evident in the XRT vs. prostatectomy debate where multiple population and retrospective analyses favored prostatectomy over XRT, which was ultimately debunked in the ProtecT trial. Lastly, there are several deficiencies in the MDT trial by Ost and colleagues, mainly that the groups were unbalanced in regard to metastatic disease burden. Dr. Dicker finishes his argument cautioning clinicians on the wide utilization of local and MDT treatments in this patient population and consider enrolling eligible patients into the available clinical trials.

Presented by: Mack Roach III MD, FASCO (Advocate), University of California San Francisco
Adam Dicker, MD, PhD, FASTRO (Skeptic), The Sidney Kimmel Cancer Center at Thomas Jefferson University

Written by: Andres F. Correa, MD, Fox Chase Cancer Center -Temple Health, Philadelphia, PA, at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA