'Revolutionary': Some Oligometastatic Cancers Are Curable

Nick Mulcahy

June 21, 2018

CHICAGO — General physicians and many oncologists probably think of metastatic cancer as being "widely disseminated and incurable" in most cases involving solid tumors in adults, said Ralph Weichselbaum, MD, a radiation oncologist at the University of Chicago here at the American Society of Clinical Oncology (ASCO) 2018 annual meeting.

But for some metastatic cancers, dissemination is limited, and such cancers may be curable with local therapy, he explained at an honorary lecture at the meeting.

The term for these cancers is oligometastatic ("oligos" is Greek for "few" or "scanty"). It was coined by Weichselbaum and colleague Samuel Hellman, MD, in an article published 13 years ago (J Clin Oncol. 1995;13:8-10).

Weichselbaum was addressing the meeting as winner of the 2018 David A. Karnofsky Memorial Award, bestowed on him by ASCO for his work in this area.

He told the audience that the concept of oligometastasis was poorly received at first. Reviewers of the pair's groundbreaking 1995 article "hated" the hypothesis, as did some of their colleagues at the University of Chicago. But the editor of the Journal of Clinical Oncology liked it, and the article was published as an editorial, said Weichselbaum.

Oligometastasis is underrecognized, but fairly common, he said.

For the four most frequent cancers in the United States, there are about 90,000 oligometastatic presentations each year, he said. These include an estimated 10,000 prostate cancers, 14,000 breast cancers, 14,000 colorectal cancers, and 50,000 lung cancers.

Another expert believes most oncologists are aware of one type of oligometastastic cancer but may not know the concept applies to all solid tumors.

It is widely recognized that some colon cancers have limited liver metastases that can be surgically removed, said Joshua Bauml, MD, a medical oncologist at the University of Pennsylvania in Philadelphia, who has written about oligometastasis. After local surgical therapy, a subset of these patients are cured. "This flies in the face of our prior understanding of what metastatic disease is," he told Medscape Medical News.

"The old paradigm of cancer metastases is, once cancer gets into [distant] lymph nodes or the blood vessels, there is no chance of cure," Bauml commented. Weichselbaum and Hellman showed that this paradigm is "not exactly accurate."

Bauml further commented: "We haven't really identified how to separate out those patients [who are curable], but just the concept that such a subgroup exists is really revolutionary."

"We haven't really identified how to separate out those patients [who are curable], but just the concept that such a subgroup exists is really revolutionary. Dr Joshua Bauml

Weichselbaum told the ASCO audience that "metastasis represents a spectrum of disease by [their] number, by [involved] organs, and by pace [of progression]."

Subsets of patients are "potentially curable" with "metastasis-directed therapies," he said. These include surgery, ablation, chemoradiotherapy, and stereotactic body radiotherapy.

Metastases are usually treated with systemic agents, which are not curative, said Weichselbaum. There are exceptions to this, including chemotherapy for germ cell tumors and immunotherapies for melanoma and certain lung cancers.

During his talk, Weichselbaum extensively discussed the role of local ablative therapy for oligometastases. Multiple randomized clinical trials have shown superior progression-free survival (PFS) in oligometastatic patients treated with ablative therapy (radiotherapy) and/or surgery compared to patients who receive standard treatment (typically, observation or chemotherapy alone). These trials include the MDACC/Colorado and UTSouthwestern trials in non–small cell lung cancer (NSCLC) and the STOMP and ORIOLE trials in prostate cancer.

There is also evidence from clinical trials that ablative therapy improves survival in patients with oligometastatic cancer, he said. For example, in a phase 2 study from the EORTC Intergroup in colorectal cancer patients with ≤10 liver metastases, the 8-year rate of overall survival with radiofrequency ablation combined with systemic chemotherapy was much better than with chemo alone (35.9% vs 8.9%; P = .01) (Ann Oncol. 2012;23:2619–2626).

The Karnofsky award winner also described research he was involved in to characterize the pathogenesis of oligometastasis; molecular subtypes complement clinical risk stratification, and gene expression informs therapy.

Multiple studies are now underway in a variety of oligometastatic cancers. In cases in which spread of the disease is limited, clinicians may want to refer patients to a trial, suggested Bauml.

An issue that "plagues" this area of cancer research is how to define oligometastases, he said. Definitions vary by researchers, and different definitions specify different numbers of metastases, as well as different locations and tumor types.

Nonetheless, researchers carry on, with some impressive results, said Bauml.

A recent randomized controlled trial showed that locally ablative therapy significantly improved median PFS in oligometastatic lung cancer patients compared to treatment without ablation (Lancet Oncol. 2016;17:1672-1682).

In this trial, all patients received initial palliative chemotherapy. Those who had persistent oligometastatic disease (and thus did not experience progression) were randomly assigned to receive locally ablative therapy plus chemotherapy or to continue palliative chemotherapy alone.

After 49 patients were randomized, the study was halted, owing to apparent efficacy. The median PFS was much better among patients who received locally ablative therapy (11.9 vs 3.9 months; P = .0054).

As a reflection of this and other research, the American Joint Committee on Cancer stage IV NSCLC guidance now indicates that patients with one or a small number of metastases can be offered definitive treatment modalities with the goal of becoming disease free.

Weichselbaum told the ASCO attendees that the "overarching clinical question for all of us, no matter what oncological discipline we're in, is, can we cure more patients with metastatic disease?"

He estimated that metastasis accounts for 85% to 90% of cancer deaths.

Fortunately, metastasis is "a very inefficient process," Weichselbaum added.

He described the process whereby tumors have to detach, survive in the circulation, adhere to the blood vessel wall, extravasate, and colonize. These processes are governed by genes and proteins, which are modified and imperfect. "So it wasn't a stretch to think that there could be a spectrum of metastasis," said Weichselbaum about his oligometastasis hypothesis.

Dr Weichselbaum has disclosed multiple relationships with industry. Dr Bauml has disclosed no relevant financial relationships.

American Society of Clinical Oncology (ASCO) 2018. Presented June 3, 2018.

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick

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