Dan Theodorescu, MD, PhD, director of the CU Cancer Center

A major symposium presented today at the American Association for Cancer Research Annual Meeting 2017 argues for the continued essential role of surgery as a pillar of multidisciplinary cancer control, even in the era of targeted treatments and immunotherapies.

“I can imagine a day when a patient could take a drug to immediately kill a large primary tumor. But we’re not there yet,” says symposium chairman Dan Theodorescu, MD, PhD, director of the University of Colorado Cancer Center.

Until then, Theodorescu suggests that continued developments in both surgery and molecular medicine are helping oncologists combine these strategies in complementary ways to target cancer and cure patients. Specifically, Theodorescu sees four ways in which surgery is and will become even more symbiotic with molecular medicine:

  1. Neoadjuvant Therapy Prior to Surgery

Neoadjuvant therapy is the use of radiation, chemotherapy or targeted treatments such as hormone therapies to shrink a primary tumor before surgery.

“In some cases, without neoadjuvant therapy, we operate on patients and in some of these patients, we just can’t get the tumor out,” Theodorescu says. Surgery augments neoadjuvant therapy, removing any residual tumor. And neoadjuvant therapy augments surgery, killing off micrometastatic disease, the small pockets of cancer outside a primary tumor that can evade surgery and that may otherwise contribute to recurrence.

  1. Molecular Staging

“There’s a big difference between cancer that is contained in a single, primary tumor and cancer that has spread. For example, a bladder cancer patient with metastasis is unlikely to benefit from bladder removal surgery,” Theodorescu says. He suggests that more accurately staging tumors, with molecular imaging techniques or tools that rely on biomarkers such as the measurement of circulating tumor DNA, will help select patients for surgery who will benefit most while avoiding unnecessary procedures for those who will not.

  1. Robotic Molecularly-Guided Surgery

“If you’re doing a prostatectomy today, you only have your eyes to tell you where the margin of the organ is and you have uncertainty if there is cancer at that margin,” Theodorescu says. An unclear tumor boundary or “margin” means that surgeons erring on the side of caution may remove more tissue than is needed, leading to additional side effects such as, in the case of prostate surgery, erectile function. On the other hand, surgeons who avoid cutting near an unclear margin may fail to resect all tumor tissue.

“Now we are starting to be able to use special dyes based on our understanding of the molecular differences between tumor tissue and healthy tissue to see this margin and other labeling technologies to see things like nerves that were hidden before even from the fantastic optics of the surgical robot,” Theodorescu says.

  1. Surgery’s Effects on the Immune System

“One of the most interesting things that surgeons have observed is that in rare cases, you operate on a primary tumor and it somehow jumpstarts the immune system’s ability to target faraway metastases. It’s a local treatment with a systemic effect,” Theodorescu says.

Theodorescu points out that efforts are underway to understand the genetic mechanisms underlying this effect as well as whether it occurs even more commonly when surgery is combined with checkpoint-directed immunotherapy. If successful, surgeons may learn to augment the immediate effects of surgery with drugs designed to elicit this effect against other sites of cancer in the body.

Today’s symposium points out that the vast majority of presentations at this scientific meeting of new techniques against cancer do not focus on surgery.

But, “Despite the excitement and promise of molecular medicines, surgery remains one of our primary tools against cancer,” Theodorescu says. “In fact, molecular medicines have enhanced surgery and surgery allows molecular medicines to blossom, a win-win scenario highlighting the need for multidisciplinary cancer care. The improvement is twofold: better cancer control with fewer side effects.”