Optimal Management of Oligometastatic Prostate Cancer Remains Unclear

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Clinical trial data for how best to treat oligometastatic prostate cancer are lacking.
Clinical trial data for how best to treat oligometastatic prostate cancer are lacking.

SAN FRANCISCO—Due to recent advances in molecular imaging, oligometastatic prostate cancer (PCa) is being diagnosed with increasing frequency. Lack of data from randomized clinical trials, however, are needed to provide guidance on the most effective treatment approach, according to Felix Y. Feng, MD, an associate professor of radiation oncology, urology, and medicine at the University of California San Francisco. In a presentation at the 2018 Genitourinary Cancers Symposium, Dr Feng said there is an urgent need for better predictors of less aggressive versus more aggressive oligometastatic disease.

“We are so early in the field of oligometastatic prostate cancer that we don't have a lot of answers yet,” Dr Feng said.

Treatment intensification approaches involve local therapy to the primary tumor, metastases-directed therapy, and intensification of systemic therapy. Little clinical evidence is available regarding the effect on these modalities with respect to overall survival (OS).

Dr Feng's presentation, Management of Oligometastatic Prostate Cancer: From Imaging to Therapy, emphasized that the use of advanced positron emission tomography (PET) imaging to detect extrapelvic disease in men with PSA recurrence has led to a new understanding of the disease. Oligometastatic PCa is defined as an intermediate state of cancer spread between localized disease and widespread metastases. Prostate-specific membrane antigen (PSMA) PET can identify oligometastatic disease at initial diagnosis, he said.

“Conventional imaging versus this has not been addressed in a clinical trial. We see a lot more disease when we use PSMA PET,” Dr. Feng said in an interview with Renal & Urology News.   “PSMA is a protein bound at the surface on prostate cells.  PSMA PET involves using an agent that binds to this PSA protein and this agent also has a radioisotope attached to it that allows for detection on a PET scan.”

Clinicians are in a conundrum when it comes to combining prostate directed therapy, systemic consolidative therapy, and node and metastasis-directed therapy (MDT). The STOMP (Surveillance or metastasis-directed Therapy for OligoMetastatic Prostate cancer recurrence) trial showed that survival free of androgen-deprivation therapy was longer with MDT than with surveillance alone for oligorecurrent prostate cancer.1 The multicenter, randomized, phase II study included 62 men with asymptomatic PCa who experienced biochemical recurrence after primary treatment. At a median follow-up time of 3 years, the median ADT-free survival was 13 months for the surveillance group compared with 21 months for the MDT group.

“It is a small study, but what it means is that if you look at 2 to 3 years after treatment about 20% of patients were free of disease,” Dr Feng. “A proportion of oligometastatic disease may be treatable.  Metastasis directed therapy by itself may not be enough if 80% of the patents are recurring in the first 2 years, so there may be need for systemic therapy in addition.”

Not all oligometastatic disease is the same, which further complicates this issue, Dr Feng said. It may be that intensification of local therapy for the primary tumor and metastases may be better than intensification of systemic therapy. In another situation, however, the opposite may be true. A biomarker is needed to distinguish high-risk from low-risk oligometastatic PCa, Dr Feng said.

In the phase II randomized ORIOLE (Observation Versus Stereotactic Ablative RadiatIOn for OLigometastatic Prostate CancEr) Trial,2 which included 54 men with hormone-sensitive oligometastatic PCa, 67% of men assigned to observation experienced disease progression at 6 months compared with only 29% of men treated with stereotactic ablative radiation, Dr Feng pointed out.

As the use of advanced PET imaging increases, “we are starting see a lot more patients with oligometastatic disease and that early trials suggest that treatment to these sites of metastasis with either surgery or radiation will improve outcomes, but only in a subset of patients,” Dr. Feng said.

Mark Garzotto, MD, professor of urology and radiation medicine at Oregon Health & Science University in Portland and the Director of Urologic Oncology at the Portland VA Medical Center, Portland, Oregon, said early detection may lead to little clinical benefit if there are no available proven therapies. “Although PSMA and fluciclovine PET are both capable of detecting metastases earlier than routine clinical imaging, it is not known if treatment of PET-only detected lesions will improve clinical outcomes,” Dr. Garzotto said.

The STOMP trial showed a trend towards delayed ADT, but failed to show a reduction in metastatic progression, he noted. An important limitation of both the STOMP and ORIOLE studies is that the investigators were unable to account for length-bias and may well have included metastatic patients with slower growing disease.  “Only large-scaled randomized trials will be able to definitely address these questions,” Dr Garzotto said.

References

1.     Ost P, Reynders D, Decaestecker K, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: A prospective, randomized, multicenter phase II trial. J Clin Oncol. 2018;36:446- 453. DOI: 10.1200/JCO.2017.75.4853.

2. Radwan N, Phillips R, Ross A, et al. A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE). BMC Cancer. 2017;17:453. doi: 10.1186/s12885- 017-3455-6.


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