Successful Resection of a Rectosigmoid Tumor After Long-term Induction Biochemotherapy – A Case Report
Neoadjuvant treatment (chemoradiotherapy) for colorectal cancer is regularly used in advanced rectal tumors, with the goal of reducing the tumor size for the surgeon and ensuring the best possible radical outcome for the patient. In metastatic tumors of the remaining parts of the digestive tract, we talk more about induction treatment, which uses a combination of targeted therapy and chemotherapy for the same purpose – reducing the extent of the tumor disease and possibly enabling surgery including radical removal of metastatic foci. The duration of this treatment is usually up to 6 months followed by surgery (surgeries). The following case report describes a successful surgical solution in a patient with an advanced sigmoid tumor even after more than 3 years of combination chemotherapy and targeted therapy.
Introduction
The only radical treatment for colorectal cancer, with some exceptions, is considered to be surgical intervention, including the removal of secondary lesions (e.g., in the lungs or liver) in cases of oligometastatic disease. In palliative treatment, combined biochemotherapy comes to the forefront, which, although not aimed at completely curing the patient, can help extend life in good quality for several years. Specific groups of these patients may also benefit from targeted therapy (in the case of a BRAF mutation) or immunotherapy (if they are mismatch repair-deficient /dMMR/ or exhibit microsatellite instability /MSI-H/).
In some cases, this type of treatment is so successful that an originally inoperable finding becomes suitable for radical removal. However, since we must first adhere to the patient's will, the effort to persuade them of the correctness of such a procedure can be lengthy and complicated. The following case report describes the story of a characteristically unique patient whose several years of palliative biochemotherapy with panitumumab in the first line led to tumor regression and, finally, a successful surgical procedure.
Case Description
The patient (*1956) presented to the doctor in July 2016, at the age of 60. The main issues were escalating pain in the rectum accompanied by gradual weight loss. Despite intensive smoking for 40 years (at least one pack of cigarettes per day), he had no other treatment, did not perceive later diagnosed chronic obstructive pulmonary disease, and initially took no medication.
As part of the diagnosis of current issues, colonoscopy and subsequently CT were performed. A circular obstructing tumor of the sigmoid colon measuring 90 mm was revealed, with regional lymphadenopathy but no distant metastases – assessed as cT4 cN1 cM0. Histologically, it was a moderately differentiated adenocarcinoma originating from the large intestine. Oncomarkers showed an elevated CEA of 47 µg/l. During the surgical procedure, the finding was deemed radically non-removable due to invasion into surrounding structures (sacrum, bladder), and only a colostomy was performed. The finding was also not considered suitable for radiotherapy.
The patient was therefore referred for the start of palliative biochemotherapy. We supplemented the examination of KRAS, NRAS, and BRAF genes – all without a proven mutation; MMR or MSI were not routinely examined at that time. A later genetic test result (the patient's father was treated for colorectal cancer at the age of 83) did not reveal any predisposition.
At the end of August 2016, the patient started treatment with a combination of panitumumab + mFOLFOX6. The biochemotherapy was well tolerated, with skin toxicity in the form of an acneiform rash bearable with local treatment with a corticosteroid and vitamin K ointment. In December 2016, after 6 cycles, CT showed a significant partial regression of the primary lesion to 45 mm, and oncomarkers normalized. An incidental finding was an asymptomatic right-sided pulmonary embolism, which was subsequently treated adequately with low molecular weight heparin (LMWH). However, the finding was still assessed as inoperable, so we continued with another 6 cycles of the same treatment.
CT of the trunk in January 2017 showed further reduction of the lesion to 32 mm, now without lymphadenopathy and also without signs of pulmonary embolism. Interestingly, the patient did not notice any symptoms of peripheral neuropathy, which was not clinically evident. He was offered the possibility of evaluation by a surgeon and reconsideration of surgical intervention, but due to his fear of surgery, we continued biochemotherapy at his request at the same dosage. Further CT examinations no longer showed tumor regression or any other finding, leading to the stabilization of the lesion size.
We continued in this way until the 25th cycle (November 2018), when a relatively rare hypersensitivity reaction related to the administration of calcium-folinate appeared for the first time. It manifested as facial flushing accompanied by chills and hypotension. The condition quickly improved after corticosteroids and antihistamines were administered. We continued with a half dose of oxaliplatin due to the onset of hematological toxicity; however, with more premedication, the treatment was again well tolerated. CT examinations continued to confirm the stabilization of the tumor process.
After a total of 34 cycles, treatment tolerance worsened as the patient felt fatigued, so we reduced it to panitumumab + FUFA. This regimen continued for 12 cycles, but towards the end, the patient felt exhausted and had issues with a parastomal hernia, and skin reactions, especially on the face, were less tolerated. After discussing it with him, we reduced the regimen to panitumumab monotherapy at 80% dose. After 12 cycles of this treatment, the patient expressed the wish to stop the treatment. We again recommended he consider surgery, especially given the increasing parastomal hernia. MRI of the pelvis demonstrated the same tumor extent as previous CTs, confirming the benefit of the targeted panitumumab monotherapy. Given the limited options due to biochemotherapy intolerance, the patient finally agreed to surgical intervention.
In November 2019, a transsphincteric resection of the rectum with hernia repair using a mesh and a terminal colostomy was performed. The surgery took place in significantly altered anatomical conditions, histologically revealing a vital cribriform moderately differentiated adenocarcinoma measuring 30 mm with necrosis foci and desmoplastic stromal reaction, occasionally showing perineural invasion but no angioinvasion; resection was assessed as R0. A total of 37 negative nodes were removed, and a 5mm tumor satellite was found. Postoperative staging pT4 pN1c.
The patient recovered well postoperatively, and the multidisciplinary team decided on adjuvant radiotherapy with modulated intensity (IMRT) of the pelvis 45 Gy/25 fractions with concomitant chemotherapy of 5-fluorouracil 200 mg/m2/day. The treatment was uneventful, and the patient remains under follow-up (as of May 2022), with no signs of tumor recurrence or dissemination. I believe that even though this decision came late, it was ultimately the right one and benefits the patient.
Discussion and Conclusion
Several interesting points emerge from this case. First, 3 years elapsed between the graphical regression of the tumor and the successful operation. This is related to the very good tolerance of the undergoing treatment (despite skin toxicity from panitumumab or hypersensitivity reaction to calcium-folinate) and the possibility of long-term administration of oxaliplatin (a total of 36 cycles) without signs of neuropathy. The described case thus illustrates the significance of multimodal treatment of colorectal cancer and further serves as evidence that it is never too late for a radical surgical procedure.
MUDr. Stanislav John
Clinic of Oncology and Radiotherapy, Faculty of Medicine, Charles University and University Hospital Hradec Králové
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