DISCUSSION

It is difficult to ascertain from our data whether patients with symptom-detected recurrences represent interval cases while on intensive surveillance, or are patients that did not adhere to surveillance recommendations. 

Indeed, though the BCCA treats most cancer patients in the province of British Columbia and this cohort is therefore a representative modern population-based sample of stage III CC, many patients are referred back to their primary care physicians for surveillance with difficult access to records.


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The median 6.8-month delay in recurrence diagnosis and age difference29 between the symptom and surveillance-detected groups would support the latter case.

However, in the FACS study, about 17% of recurrences in the CEA/CT surveillance arm were interval cases20, which is comparable to the proportion of symptom-detected recurrences in our study.

Due to this issue, it is difficult to compare our results with studies including patients assigned to minimal or no surveillance.

Regardless of this point, it is concerning for intensive surveillance policies that patients with asymptomatic recurrences did not have an OS benefit compared with patients with symptomatically detected recurrences.

This is particularly puzzling given that the former group received more potentially curative metastasectomy and chemotherapy.

Furthermore, the potential length time bias from some symptom-detected recurrences being interval cases should have disadvantaged this group in survival analyses.

Nonetheless, around 50% of the symptom-detected group did receive at least 1 line of chemotherapy, and a couple of patients underwent potentially curable metastasectomy, thereby perhaps mitigating any OS benefit from asymptomatic detection. It is difficult to compare our results given many of the surveillance RCTs do not report post-recurrence chemotherapy treatment rates12-20.

It is clear, however, that some symptomatic recurrences remain resectable as observed in this study and reported elsewhere in the literature30. Of course, there was an 11.8-month OS trend (P=0.091) in favor of the former group that may have become significant with increasing sample size.

This further supports the point, also noted in the FACS trial20, that if there is a survival benefit to any surveillance strategy in unselected patients, it is likely small.

The results of this study should not dissuade physicians from enrolling stage III CC patients onto intensive surveillance protocols.

Complete resection of liver and/or lung metastases in appropriately selected patients is associated with favorable long-term survival7,8,31, and this study showed patients with asymptomatic recurrences are more likely to undergo potentially curative metastasectomy.

Furthermore, given chemotherapy treatment of asymptomatic metastatic disease improves survival32, a higher probability of receiving chemotherapy offers an opportunity to increase OS with improving chemotherapy treatment options.

Rather, our results should serve to justify further study into identifying subsets of patients that may benefit most from intensive surveillance, and defining the optimal surveillance sequence. The ongoing GILDA and COLOFOL trials should shed some light on the latter question27,28.

We restricted our analysis to stage III CC patients, who have the highest risk of recurrence. Interestingly, the FACS study showed approximately 5% of patients with stages I, II and III underwent potentially curative resection, suggesting intensive surveillance offers a similar benefit across stages of disease.

However, given the overall lower risk of recurrence in earlier stages of disease, potentially curative resections play a proportionately greater role in stage I and II CC. Future population based research should evaluate the impact of surveillance on earlier stages of disease.

The strength of our study is that it offers insight into real world practice with a modern population-based cohort of moderate size.

Furthermore, to our knowledge, this is the only study to only include stage III CC patients, who have the highest risk of recurrence. Limitations include the retrospective nature and lack of detailed data on surveillance follow-up. However, many of our findings are in agreement with the known literature.

CONCLUSIONS

The OS impact of detecting an asymptomatic recurrence in stage III CC is unclear. However, patients with asymptomatic recurrences are more likely to receive potentially curative metastasectomy and chemotherapy.

Acknowledgments

Authors’ contributions: RD Peixoto designed the overall study with contributions from M Smoragiewicz and H Lim. RD Peixoto and M Smoragiewicz collected and analyzed data, and co-wrote the paper. RD Peixoto, H Lim and M Smoragiewicz discussed and edited the paper.

Disclosure: The authors declare no conflict of interest.


Martin Smoragiewicz, Howard Lim, Renata D’Alpino Peixoto

Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada

Correspondence to: Dr. Martin Smoragiewicz, MD, CM, BSc. Department of Medical Oncology, British Columbia Cancer Agency, 600 West 10thAvenue, Vancouver, BC V5Z 4E6, Canada. Email: [email protected]


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Source: Journal of Gastrointestinal Oncology.