Confronting Colorectal Cancer: A No-Holds-Barred Approach
March is colorectal cancer awareness month.
Colorectal cancer is the third most common cancer for both men and women in the US with 101,420 new colon and 44,180 new rectal cancers diagnosed and 51,000 deaths attributed to this disease in 2019.
The good news is that death from colorectal cancer continues to decline. Routine screening and newer diagnostic technologies are having an impact upon this disease.
Despite this, certain trends, including an alarming rise in the risk for rectal cancer in patients under 40, that may reflect diet or lifestyle, warrant our continued attention.
Stages of Colon Cancer
Colon cancer is managed by stage with earliest stage (I) usually cured with surgery.
Stage II is more invasive but can often be cured with surgery as well. Once the disease has spread to the lymph nodes, (Stage III) it requires postoperative (adjuvant) chemotherapy.
Stage IV is the most advanced presentation meaning that the cancer has already spread to distant sites by the time of diagnosis. The most common finding in Stage IV is metastases to the liver.
Update: A Case of Stage 4 Colon Cancer
As I am reminded of one of my own colon cancer patients about whom I wrote a blog dated 01/31/2017, this serves as an update on his case.
I first met the patient on 01/15/2016 after his wife encouraged him to have a blood test called a CEA with his routine laboratories. The results returned at 619, over a 100-fold elevation.
A workup followed and identified multiple liver metastases, biopsy of which confirmed adenocarcinoma of the colon. The primary was subsequently found at colonoscopy.
Additional liver biopsies allowed us to profile the patient.
With a favorable signature, an aggressive combination of chemotherapy drugs provided a biochemical remission associated with near complete resolution of measurable disease by PET/CT.
He was referred to surgery for resection of the liver metastases and removal of the colon primary.
Additional chemotherapy followed by yttrium Y-90 Thera-Sphere consolidated his good response. At the one-year point, his good results served as the subject of my 2017 blog.
In 2018, a rise in the CEA led restaging which revealed a new nodule in the left lower lobe of the lung. Our thoracic surgeon removed the lesion and a new treatment regimen was identified that targeted both VEGF and EGFR in combination with Irinotecan similar to a prior clinical report known as the BOND-2 trial. The patient's tumor markers promptly declined and he remained well.
In late 2018 a small rise in the CEA led to the finding of a small focus of uptake in the left lobe of the liver. We opted for focused radiation known as CyberKnife and the new focus of disease was eradicated. The CEA fell by 50% and now approaches normal.
The patient continues his medical practice and remains active, vigorous and well, now over three years since diagnosis.
His case is a lesson in human tumor biology.
First, he had exactly the right characteristics for the most aggressive drug combinations. We used not only epidermal growth factors inhibitors, but vascular endothelial growth factor inhibitors to achieve his remissions.
Second, we consolidated his good results with surgery and radiation both of which are modalities of therapy that are not directly cross-resistant with chemotherapy.
Third, the evolution of a new cancer clone, heralded by a lung recurrence, allowed us to harvest cancer cells, re-evaluate and then treat according to the new biological features.
Finally, the successive sub-clones identified at each biopsy, when individually addressed and eliminated may now have left the patient with little or no residual disease.
From a strategic standpoint, our approach was to eliminate the founder clone (ancestral tumor origin) of his cancer and then to successively eliminate each of the new branches budding from this original population until the tumor ran out of branches.
This represents a fundamental change in the treatment of cancer and is made possible by our unique capacity to study each new clone as it arises in new anatomic sites.
Had we not resected the lung tumor, we would not have seen the new pattern of sensitivity and might have failed to make the appropriate adjustments in treatment to eradicate that new subpopulation.
Cancer therapy is not unlike the cartoon series "The Road Runner." Medical oncologists like Wile E. Coyote attempt to corral their adversary with the "ACME" chemotherapy products du jour, but more often than not find their efforts foiled.
We need to outsmart cancer like the road runner by anticipating its every move and capturing it at the very moment that it thinks it has finally escaped. To defeat your enemy, you must know your enemy and to know your enemy you must study your enemy.
Our tumor primary-culture analyses may offer the opportunity for us to successfully confront our patient’s cancers, in all their nuanced forms, with curative intent.
As always, I appreciate your thoughts and comments.