A 72-year-old man diagnosed with a T3N1 bleeding low rectal mass and two synchronous 3-cm hepatic metastases in segment VI of the right hemiliver. A PET scan showed no evidence of extrahepatic disease. To facilitate sphincter preserving rectal surgery, he received neoadjuvant infusional 5-FU, weekly oxaliplatin and radiation therapy. Six weeks after completion of treatment his rectal lesion notably regressed and his liver metastases decreased in size. He then underwent a low anterior resection of his primary tumor and a simultaneous wedge resection of the liver lesions. Postoperatively, he received six cycles of FOLFOX.
Case Discussion:
DR HALLER: This 72-year-old man initially presented with three months of tenesmus and rectal bleeding. A rectal mass was observed on colonoscopy, located four centimeters from the anal verge, and an endoscopic ultrasound showed it was a T3N1 tumor. This case exemplifies the need for a multimodal approach, including a gastroenterologist and a colorectal surgeon to perform the endoscopic ultrasound. Pretreatment staging revealed two 3-cm hepatic lesions in segment VI of the right lobe on CT, and a PET scan showed no other evidence of metastases.
We didn’t perform the liver surgery up front, because the patient was symptomatic and needed to be treated for his rectal cancer. We know that with infusional 5-FU/oxaliplatin and radiation therapy, most patients stop bleeding after the first week of treatment. Also, based on the location of the tumor, we felt in our multimodal conference that this patient needed downstaging to preserve the sphincter, if at all possible.
Currently, two large clinical trials are underway evaluating whether oxaliplatin adds benefit to radiation therapy in the neoadjuvant setting, including NSABP-R-04. Pending the results of that study and given the large number of Phase II data, we elected to use this approach. We also did it to control the hepatic metastases.
He received infusional 5-FU, weekly oxaliplatin and radiation therapy. Many studies with oxaliplatin/5-FU and radiation therapy suggest a higher pathologic complete response rate. He received all of his treatment without difficulty and his symptoms improved within the first three weeks of starting therapy.
I generally use infusional 5-FU rather than capecitabine as adjuvant therapy for rectal cancer. No prospective data show that we can substitute with capecitabine in this setting, although it is implied that we can based on rough equivalency in advanced disease. However, in the adjuvant setting, the solid data are with infusional 5-FU.
Nor do I use CAPOX rather than FOLFOX. I am waiting for data from the AVANT trial — evaluating the addition of bevacizumab to either adjuvant FOLFOX4 or CAPOX in Stage II and III colon cancer — to show whether they are equivalent. Though they appear roughly equivalent or noninferior for capecitabine/oxaliplatin in advanced disease, even a small decrement in activity in the adjuvant setting might mean a difference in cure rate. Thus, I tend to be much more rigid in my approach in the adjuvant setting, and less so in the metastatic setting in which I have multiple chances to treat. We usually have only one chance to cure the patient.
On the other hand, if a patient had an infected port and refused to be treated again with infusional 5-FU, I’d probably administer capecitabine, based on the NSABP dose and schedule, rather than bolus 5-FU.
Six weeks after completing the treatment, the patient’s disease was restaged by sigmoidoscopy. Many clinicians would wait 10 weeks to allow for maximal tumor regression. Even if he could have gone to the operating room a week after his chemotherapy and radiation therapy, it’s not a good thing to do because regression continues for six, eight or even 10 weeks. If sphincter preservation is important, then you want the tumor to be as small as possible.
This patient’s primary tumor had decreased to a small ulcer and a biopsy showed scattered tumor cells. On CT, the hepatic lesions had each decreased by about 50 percent and the PET showed no new lesions. The SUV of the original lesions, which had been around six or eight, were now three to four.
The patient was able to undergo a low anterior resection of his primary tumor and a simultaneous wedge resection of the liver lesions. This extended surgery by perhaps an hour, but he did not have any major comorbidities, so everyone felt comfortable with this including the anesthesiologist. Had the patient required an extended right hepatectomy, which would have been a two or three-hour operation, we probably would have performed the liver resection first and done his rectal surgery later since he had such a great response from his primary treatment.
Pathology revealed that the primary tumor was downstaged to a T2N0, and the liver lesion contained a few scattered tumor cells and had negative surgical margins, so it was a R0 resection. He was then scheduled to receive six cycles of postoperative adjuvant FOLFOX, which has been pretty much standard treatment at our institution.
