ASCO GU 2020: Targeted Therapy in the Context of Low Volume Metastatic Prostate Cancer

San Francisco, California (UroToday.com) Dr. Michael Morris presented about targeted therapy for low volume and oligometastatic prostate cancer, which is a highly dynamic topic with more data added each year. The distribution of metastatic disease is not just a measure but a complete framework,according to Dr. Morris. It has been shown the metastasis develops not only from the primary tumor but from other metastasis as well in metastasis to metastasis seeding pathway1 (Figure 1).

Figure 1 - Metastasis to metastasis seeding pathway:

MorrisFigure1.png

According to the CHAARTED criteria,2 low volume metastatic disease was anything other then the defined criteria for high volume metastatic castrate sensitive prostate cancer which includes:

  • 4 or more bone lesions and
  • one or more lesion in any Bony structure beyond the spine or pelvis
  • or visceral disease (non-nodal)

It is not clear whether low volume disease is oligometastatic disease or high-volume widespread disease. Low volume disease agnostic to any amount of nodal disease. High volume disease by visceral disease can be oligometastatic. To date, no term accounts for liquid assessments of disease burden or biologic or genomic characterization. The currently used terminology is confusing, misleading and inconsistent, as can be seen in figure 2.

Figure 2-Confusing terms currently used for metastatic disease:

MorrisFigure2.png
There are several types of oligometastatic disease defined to date3:

  • Synchronous which is primary and oligometastatic
  • Metachronous which is primarily followed by oligometastatic relapse
  • Oligoprogressive-Which is a progressive event through systemic therapy

The current advancement in molecular imaging is changing the definition of metastatic disease. Additionally, we have inconsistent standards for the treatment of oligometastatic disease. We currently have level one evidence from well-conducted phase three randomized prospective trials showing that androgen receptor directed therapy improves overall survival in M1 disease (Table 1). Moreover, we have evidence showing that in low volume metastatic disease radiotherapy to the primary tumor prolongs overall survival as well (Figure 3).

Table 1–Level 1 evidence of AR-directed therapy improving overall survival in M1disease:

MorrisTable1.png

Figure 3–Radiotherapy treatment of the primary tumor in low volume metastatic disease Prolongs overall survival:

MorrisFigure3.png
Additionally, there are other ongoing trials attempting to ascertain whether treatment of the primary tumor with either surgery or radiotherapy improves outcomes (Table 2).

Table 2-Current trials assessing whether treatment of the primary tumors in metastatic disease improves outcome:

MorrisTable2.png
Lastly, there are ongoing trials assessing whether radiotherapy treatment of de novo synchronous metastasis in addition to the treatment of the primary tumor will improve outcomes (Table 3).

Table 3-trials testing radiotherapy to metastatic sites and treatment of the primary tumor with systemic therapy: 

MorrisTable3.png

Dr. Morris concluded his presentation by reiterating that there is variable terminology regarding the terms of oligometastatic and low volume disease. Additionally, the standards of care should be defined by uniform levels of evidence. It is still not clear if eliminating all visualized in seen through novel advanced imaging will definitively result in benefit. One thing is certain-this field warrants significantly more study and research.

Presented By: Michael J. Morris, MD, Medical Oncologist Clinical Director, Genitourinary Medical Oncology Service & Prostate Cancer Section Head, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Written By: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA @GoldbergHanan at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
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