Improving surgical therapy for oesophageal cancer

Despite advances in multimodality treatment, surgery remains the mainstay of curative treatment for oesophageal cancer. However short- and long-term mortality from oesophagectomy for oesophageal cancer still shows large variations nationally and internationally. This thesis addresses three themes concerning oesophageal cancer surgery.

The first theme focuses on technical challenges, learning in surgery and the influence of surgeon age on outcomes from oesophagectomy. Study I utilised a large French multi-centre database (FREGAT), and showed in contrast to previous smaller single-centre studies, salvage oesophagectomy after definitive chemoradiotherapy can offer acceptable short- and long-term outcomes in selected patients at experienced oesophageal cancer centres. Study II used a national Swedish dataset (SESS) and demonstrated that the period during which surgeons gain proficiency in performing oesophagectomy for cancer is associated with substantial adverse effects upon short- and long-term mortality at a national level. The length of the proficiency gain period was longer for long-term mortality than for short-term mortality, implying a change in surgeon focus during the initial stages of their independent practice. Study III also used the SESS and was able to show the optimal surgeon age in performing oesophagectomy in Sweden is between 51 and 56 years. Outside of this age period, increases in short- and long-term mortality are noted, as surgeons are still gaining experience or maybe experiencing decline in their technical abilities.

The second theme, sought to evaluate the effect of hospital factors, which may affect outcome from oesophagectomy for cancer. Study IV used SESS once more, and showed surgery performed in university hospitals has no improvements in long-term mortality from oesophagectomy after adjustment for surgeon volume and other confounders. The third theme of this thesis considered the effect of complications during treatment for oesophageal cancer upon long-term prognosis. Study V used FREGAT and demonstrated severe oesophageal anastomotic leak following oesophagectomy for cancer, adversely impacts cancer prognosis with a decrease in overall and disease-free survival and an increasing in overall, loco-regional and mixed cancer recurrence.

In conclusion, the studies conducted within this thesis have shown the safety of new therapeutic surgical strategies for oesophageal cancer, the importance of surgeon proficiency gain and surgeon age in prognosis, the lack of significance of university hospital status, and the adverse long-term prognostic effects of severe oesophageal anastomotic leak.

List of scientific papers

I. Markar SR, Gronnier C, Duhamel A, Pasquer A, Thereaux J, du Rieu MC, Lefevre JH, Turner K, Luc G, Mariette C, on behalf of the FREGAT working group –FRENCH-AFC. Salvage Surgery after Chemoradiotherapy in the Management of Esophageal Cancer: Is it a viable therapeutic option? Journal of Clinical Oncology. 2015; 33: 3866–73.
https://doi.org/10.1200/JCO.2014.59.9092

II. Markar SR, Mackenzie H, Lagergren P, Hanna GB, Lagergren J. Surgical Proficiency Gain and Survival after Esophagectomy for Cancer. Journal of Clinical Oncology. 2016; 34: 1528–36.
https://doi.org/10.1200/JCO.2015.65.2875

III. Markar SR, Mackenzie H, Lagergren P, Lagergren J. Surgeon Age in Relation to Prognosis after Esophageal Cancer Resection. Annals of Surgery. 2017.
https://doi.org/10.1097/SLA.0000000000002260

IV. Markar SR, Wahlin K, Lagergren P, Lagergren J. University hospital status and prognosis following surgery for esophageal cancer. European Journal of Surgical Oncology. 2016; 42: 1191–5.
https://doi.org/10.1016/j.ejso.2016.05.028

V. Markar SR, Gronnier C, Duhamel A, Mabrut JY, Bail JP, Carrere N, Lefevre JH, Brigand C, Vaillant JC, Adham M, Msika S, Demartines N, Nakadi IE, Meunier B, Collet D, Mariette C, on behalf of the FREGAT working group –FRENCH-AFC. The Impact of Severe Anastomotic Leak on Long-term Survival and Cancer Recurrence after Surgical Resection for Esophageal Malignancy. Annals of Surgery. 2015; 262: 972–80.
https://doi.org/10.1097/SLA.0000000000001011