A South Australian farmer with stage 4 melanoma has achieved complete and durable remission following open-heart surgery without sustained targeted cancer therapy or immunotherapy, with the response persisting for six years.
Writing in BMJ Case Reports [link here], his oncologists said the “highly exceptional” case supported a hypothesis that surgery-associated systemic immune activation might contribute to long-term tumour control.
The man in his mid 60s, who had a history of resected primary cutaneous melanoma, was undergoing cardiac workup for symptomatic aortic stenosis when doctors first discovered signs of metastatic BRAF V600E mutant disease.
Later imaging revealed lymph node, liver and bone involvement.
The patient was treated with BRAF and MEK inhibitors (dabrafenib 150 mg twice daily and trametinib 2 mg once daily), but stopped after just two months due to multiple side effects (high fever, lethargy and coryzal symptoms and later grade 3 hepatotoxicity following rechallenge), subsequently experiencing progression.
He was briefly trialled on vemurafenib (960 mg) and cobimetinib (60 mg) for six days, but developed rigours, chills and grade 3 fatigue.
During this time, his valvular disease deteriorated, prompting surgical aortic valve replacement with coronary artery bypass grafting. Recovery was complicated by infection with the patient requiring surgical washout and closure of a wound and a short course of antibiotics.
Unexpectedly, restaging imaging just three weeks after surgery revealed the patient’s complete resolution of malignant nodal, hepatic and bony disease.
Initially scheduled to start second-line immunotherapy after recovery from cardiac surgery, the patient’s treatment was delayed until evidence of recurrence. This never occurred, said the treating oncologists from Royal Adelaide Hospital.
The patient remains under active surveillance with scans every six months, but six years after surgery, he continues to show no evidence of recurrence.
“Long-term remission extending beyond 5 years without ongoing treatment is highly unusual and inconsistent with what would be expected from limited, interrupted MAPK pathway inhibition alone,” the report authors said.
They suggested that surgical trauma and post-operative infection might have contributed as immune triggers, pointing out that such inflammatory stimuli had been associated with rare cases of spontaneous melanoma regression.
“Given this patient’s documented progression immediately before surgery and complete disappearance of all measurable disease soon afterward, it is plausible that the inflammatory milieu generated peri-operatively broke the pre-existing immune tolerance, enabling recognition of melanoma antigens and thus creating durable cytotoxic immune activity,” they said.
Interestingly, two years after surgery, the patient developed a new honeybee allergy, with his doctors noting onset was uncommon in adulthood and provided further support for significantly altered immune regulation and reactivity.
“This case highlights the need for further investigation into how surgery-related inflammation, antigen release and immune reprogramming may interact and result in beneficial clinical outcomes in metastatic melanoma,” they concluded.