Nicholas Hornstein, Assistant Professor at Northwell Health, shared a post on LinkedIn about a recent article by Yukihide Kanemitsu et al, published in Journal of Clinical Oncology:
“Adjuvant chemotherapy works in colorectal cancer… right?
When it comes to resectable colorectal liver metastases, the answer may be more complicated than we like to admit.
JCOG0603 was the first randomized trial to test adjuvant doublet chemotherapy after hepatectomy in CRLM. The headline result was familiar: adjuvant mFOLFOX6 improved disease free survival. But with long term follow up, overall survival told a very different story. There was no OS benefit compared with surgery alone, despite years of additional follow up. This mirrors what we have already seen with EORTC 40983 and New EPOC.
Why the disconnect?
- The trial was powered for DFS, not OS
- Oxaliplatin alters liver parenchyma, making CT based DFS a potentially unreliable surrogate
- Patients in the surgery only arm had more effective salvage surgery and greater reuse of oxaliplatin at recurrence
- Toxicity mattered, with high rates of severe neutropenia, poor chemotherapy completion, and even rare treatment related death
The bigger lesson is uncomfortable but important. In resectable colorectal liver metastases, delaying radiographic recurrence does not necessarily translate into living longer or living better. Post recurrence management, surgical salvage, and tumor biology may matter far more than perioperative chemotherapy intensity.
For me, this argues against routine adjuvant mFOLFOX after hepatectomy and toward more selective, biology driven decision making.
At the same time, this is not an easy ‘don’t treat’ scenario. We lack clearly superior alternatives, and choosing not to give systemic therapy in a high risk disease is hard for clinicians and patients alike.
If anything, JCOG0603 highlights the real unmet need in CRLM: better studies, better biomarkers, and better drugs. This disease keeps surprising us, and this is one of the most important reminders why.”
Title: Randomized Phase II/III Trial Comparing Hepatectomy, Followed by mFOLFOX6 With Hepatectomy Alone for Liver Metastasis From Colorectal Cancer: Long-Term Results of JCOG0603
Authors: Yukihide Kanemitsu, Yasuhiro Shimizu, Junki Mizusawa, Yoshitaka Inaba, Shunsuke Tsukamoto, Atsuo Takashima, Masayuki Ohue, Koji Komori, Akio Shiomi, Manabu Shiozawa, Yusuke Suwa, Takeshi Suto, Yusuke Kinugasa, Yasumasa Takii, Hiroyuki Bando, Takaya Kobatake, Masafumi Inomata, Yasuhiro Shimada, Hiroshi Katayama, Haruhiko Fukuda
Read the Full Article on Journal of Clinical Oncology
More posts featuring Nicholas Hornstein.
