Cancer recurrence linked to residual disease missed by imaging

A new editorial was published in Oncotarget, Volume 16, on March 13, 2025, titled "No disease left behind."

In this editorial, Dr. Muzamil Arshad from the University of Chicago Medical Center and colleagues highlight a growing concern in cancer care: radiotherapy may leave behind microscopic cancer even when scan images suggest the tumor is gone. The authors argue that this "residual disease" is more common than expected and is linked to worse long-term outcomes. Their perspective calls for a rethinking of how treatment success is judged and how cancer is followed up after therapy.

Radiotherapy, especially a form known as stereotactic ablative radiotherapy (SABR), is widely used to treat cancers in the lung, liver, prostate, and other organs. SABR delivers high-dose radiation with outstanding precision and often shows excellent results on scans. However, the authors highlight that relying only on imaging may not provide a complete picture. Months or even years later, follow-up biopsies frequently reveal cancer cells that scan imaging tests were unable to identify.

"Residual cancer is identified on histology in 40% of lung, 57–69% of renal cell, 7.7–47.6% of prostate and 0–86.7% of hepatocellular carcinoma."

This gap between what scans show and what tissue analysis finds can have serious consequences. Studies across several cancer types have shown that patients with residual disease-even if small-are more likely to experience cancer recurrence and shorter survival. This pattern holds true for rectal, cervical, prostate, and liver cancers, among others. In some cases, not destroying the tumor completely may allow it to spread to distant organs.

The authors point out that a complete response on scan imaging does not necessarily indicate the complete disappearance of the tumor. This mismatch can mislead both clinicians and patients into thinking treatment was more successful than it truly was. The editorial encourages more regular use of biopsy-based tests and new strategies to increase the true effectiveness-or "ablative power"-of SABR.

They also discuss promising approaches to improve outcomes, including increasing radiation doses and combining radiotherapy with other therapies, such as immune checkpoint inhibitors. While some trials have shown better tumor control with these combinations, results have not been consistent, and more research is needed to refine these strategies.

In summary, this editorial encourages the cancer care community to look beyond the scan images. Residual cancer may remain even when imaging looks clear, and recognizing this hidden threat is key to improving long-term outcomes. The goal is not just to shrink tumors on screen but to fully eliminate the disease.