Targeted Therapies Include Targeted Surgery

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The term “targeted therapy” has entered the oncologic lexicon over the past five years, with primary applications in medical and radiation oncology. In medical oncology, the term refers to the ability of new systemic treatments to zero in on aberrant proteins or receptors expressed solely or disproportionately in transformed tissues.

Unlike classic chemotherapy, which kills both normal and malignant dividing cells, targeted therapies promise higher response rates with fewer adverse effects. The impetus for targeted therapy in medical oncology is our burgeoning understanding of the molecular biology of cancers. This is well exemplified in the treatment of kidney cancer.

To a radiation oncologist, targeted therapies means radiating cancerous tissues or organs more precisely, allowing higher dose delivery with fewer toxicities. In prostate cancer therapy this is soundly demonstrated, in that the classic four-field conventional approach was replaced first by 3D conformal and now by intensity modulated radiation therapy.

More recently, image-guided technologies such as ultrasound, cone beam CT, and 3D organ tracking with implanted beacons are allowing further dose escalation and reduction of normal tissue radiation exposure. Here, the target is the organ and the impetus is improvements in technology.

What does targeted therapy mean to a surgical oncologist? Organ preservation? Robotic approaches? Probably the answer is more fundamental. The true targeted surgical approach should match the biology of the tumor. This requires the ability to distinguish localized tumors with minimal metastatic potential from those that are systemic from inception, and all gradations in between, and then target cases whose biology is surgically most relevant.

This concept was well enunciated by Dr. Whitmore decades ago when, in regard to prostate cancer, he said we should be guided by this question: “Is cure possible in those in whom it is necessary, and is it necessary in those in whom it is possible?” Cogent data exist to support similar approaches in many solid tumors. 

Targeting surgical therapies to a tumor's biology will require improvements in molecular medicine, imaging, biomarkers, and outcomes analyses. In this era of targeted therapies, surgeons must
understand that the target is not simply safe excision but more importantly an understanding of how and if surgery will alter a tumor's inherent biology.

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