Is There Evidence for Local Treatment for Newly Diagnosed Metastatic Prostate Cancer?

During a session at the 2018 Genitourinary Cancers Symposium, 2 doctors debate whether there is existing evidence for local treatment for patients newly diagnosed with metastatic disease.

Case: A 75-year-old white male presents with an elevated prostate-specific antigen of 10 ng/dL found during an annual routine examination. He was found to have a mildly enlarged prostate and a family history of prostate cancer with his father having been diagnosed with prostate cancer at 69 years old. The biopsy showed multiple cores with Gleason 9 on both sides. He had a computated tomography scan of the abdomen and pelvis, which did not show any evidence of metastatic disease, but his bone scan identified 4 suspicious areas (right iliac crest, left eighth rib, right sixth rib, and T12).

The patient was started on androgen deprivation therapy and a thorough discussion was held with him with regards to the role of docetaxel versus abiraterone/prednisone. The patient ultimately decided on docetaxel for 6 cycles and did well. But, at a subsequent visit he asked a question: "How much more aggressive can I be in this setting when you tell me I have relatively minimal disease in terms of the metastatic picture? Should there be a role of aggressive local therapy now that I have done what I can with systemic treatment?"

Question: Is there evidence for local treatment in patients with newly diagnosed metastatic disease?

Debate: According to Mack Roach III, MD, FASCO, professor of radiation oncology and urology, University of California, San Francisco: “It’s clear that there’s evidence. The area that I would surrender to is how good is the evidence? But, the evidence is nonetheless there.”

Roach stressed that while there is a lack high-level evidence, there is evidence, and patients want it. There are studies that support the notion that even people with metastatic disease benefit from local treatment, he added.

He used the example of a trial of patients with lung cancer who were randomized to receive treatment to their metastases in addition to primary treatment, and results suggested there was a progression-free advantage when both were addressed.

He then tied it in with the STOMP trial, where 62 patients either received surveillance or a metastasis-directed therapy (MDT) for oligometastatic prostate cancer recurrence. The patients had fewer than 4 extracranial metastases and serum T levels over 50 ng/mL. Patients were randomly assigned 1:1 to either surveillance or MDT of all detected lesions. The primary endpoint was freedom from androgen depravation therapy. Results showed there was a suggestion of a benefit favoring the patients who had MDT.

“The devil in the details is that these patients had to have their primary controlled,” said Roach. “So, when you try to infer from these data how they relate to the case of the patient whose presenting with a primary that has not been treated, you really can’t use the STOMP data, because these are people failing with metastatic disease. So, if you want, you infer, you must control the primary and treat the metastases, and there’s evidence that both of these things might impact the patient’s outcome.”

There’s clear evidence that local treatment is beneficial, but we need to better select which patients are the ones who are likely to benefit, he concluded.

However, Adam Dicker, MD, PhD, FASTRO, senior vice president, professor and chair, Department of Radiation Oncology, The Sidney Kimmel Cancer Center at Thomas Jefferson University, was skeptical, and said that by treating the primary and the metastases, it’s still unclear you can affect the progression of disease.

“The human data suggests that from limited studies, that most metastases come from other metastases, not the primary,” said Dicker. “So, the role of the primary in the control department is very unclear at this time, although there’s some papers of isolated cases focusing on the primary.”

Addressing Roach’s STOMP trial connection to small cell lung cancer trial he said: those are patients with metastatic lung cancer who are treated with systemic therapy, or checkpoint therapy. For those patients who have a response and for those patients who are remaining on treatment, we are simultaneously treating the primary and the metastasis. Meanwhile, in the STOMP trial, the primary was treated and at some point in the future, the patient developed a metastasis. We don’t know how to sequence the treatment of these types of therapies, said Dicker.

“I’d say we don’t know enough,” he concluded. “Precision medicine approaches, rational combination approaches, patient-reported outcomes, and patient-generated data should be investigated, and all treatment has toxicity. In summary, we don’t know what we don’t know, thus do no harm.”