Interventional procedure overview of maximal effort cytoreductive surgery for advanced ovarian cancer

Quality of life

In a NICE-commissioned UK multicentre cohort study of 247 patients with late-stage ovarian cancer who had cytoreductive surgery of varying complexity with the aim of complete tumour clearance, quality of life improved in all groups with no clinically meaningful differences in quality of life among patients undergoing surgery of different complexities. The mean change in score from baseline in the EORTC QLQ-C30 at 6 weeks after surgery was 3.4 (SD 1.8, n=88) in the low SCS group, 4.0 (SD 2.1, n=55) in the intermediate SCS group and 4.3 (SD 2.1, n=52) in the high SCS group (p=0.048). At 12 months the mean change was 4.3 (SD 2.1, n=51) in the low SCS group, 5.1 (SD 2.2, n=41) in the intermediate SCS group and 5.1 (SD 2.2, n=35) in the high SCS group (p=0.133). In all patients, there was a small statistically significant improvement in quality of life after surgery at the 12 month follow up (p<0.001). Patients in the high SCS group had small to moderate decreases in physical (p=0.004), role (p=0.016) and emotional (p=0.001) function at 6 weeks after surgery, which resolved by 6 to 12 months (Sundar 2022).

Overall survival

In a cohort study of 1,471 patients, treatment centres were categorised by patterns of surgical practice (mainly high SCS, mainly intermediate SCS and mainly low SCS). Median survival was 23.1 months (95% CI 19.0 to 27.2 months) in the mainly high SCS centres, 22.0 months (95% CI 17.6 to 26.3 months) in the mainly intermediate SCS centres and 17.9 months (95% CI 15.7 to 20.1 months) in the mainly low SCS centres. Compared to patients in the high SCS centres, patients in the low SCS group centres had a hazard ratio of 1.21 (95% CI 1.04 to 1.40) for death (Cummins 2022).

In the cohort study of 247 patients, overall survival at 2 years was 83% in patients with no residual disease after surgery and 64% in patients with residual disease (p<0.001; Sundar 2022).

In a population-based cohort study of 3,728 patients with primary stage 3C or 4 cancer of the ovary, fallopian tube, peritoneum or undesignated primary site, survival improved after national guidelines for ovarian cancer were implemented. After adjusting for age and stage, the excess mortality rate ratio was 0.89 (95% CI 0.82 to 0.96, p<0.05). In those patients who had primary debulking surgery, median overall survival was 35 months (95% CI 32.8 to 39.2) before the guideline was implemented compared with 43 months (95% CI 40.9 to 46.4) after. The median survival where R0 (no residual tumour) was achieved was 59.0 months (95% CI 53.6 to 66.1) compared with 32.5 months (95% CI 29.9 to 34.6) for those with residual tumour (Dahm Kahler 2021).

In a population-based cohort study of 752 patients with advanced epithelial ovarian cancer, comparing those who were treated before and after a paradigm shift to upfront ultra-radical surgery reported that there was no difference in 5-year overall survival irrespective of treatment modality (HR 1.03, 95% CI 0.87 to 1.22, p=0.75). The subgroup of patients with high SCS had inferior survival in the later cohort (HR 1.99, 95% CI 1.12 to 3.56). The median survival for patients in whom radical resection was achieved was 58 months in the earlier cohort and 55 months in the later cohort (HR 1.31, 95% CI 0.89 to 1.92, p=0.17; Falconer 2020).

In a retrospective analysis of chemotherapy trials, 2,655 patients with advanced epithelial ovarian cancer or primary peritoneal cancer who had primary cytoreductive surgery to achieve complete surgical resection or less than 1 cm residual disease, median overall survival was 48.7 months in those who had low SCS surgery, 48.4 months in those who had moderate SCS surgery and 44.2 months in those who had high SCS surgery (p=0.191). For patients who had complete resection, median overall survival was 76.9 months compared with 40.6 months for those with residual disease (p<0.01; Horowitz 2015).

In a cohort study of 978 patients with advanced ovarian cancer who had primary debulking surgery, 5-year overall survival was 40% in those who were treated between 2001 and 2005, 44% in those who were treated between 2006 and 2009 and 56% for those who were treated between 2010 and 2013 (p<0.001). During this time, extensive upper abdominal procedures started to be incorporated and the goal for primary debulking surgery evolved from residual disease 10 mm or less to either complete gross resection or as minimal residual tumour as possible (Tseng 2018).

In a cohort study of 608 patients with stage 3 or 4 advanced ovarian cancer who had cytoreductive surgery, median overall survival was 48.2 months (95% CI 40.6 to 55.8 months). In patients who had primary debulking surgery and complete cytoreduction, the median overall survival had not been reached. The estimated mean overall survival was 83.9 months (95% CI 75.2 to 92.7 months). In patients who had primary debulking surgery and optimal or suboptimal cytoreduction, the median overall survival was 56.3 months (95% CI 25.8 to 86.8 months) and 15.0 months (95% CI 9.1 to 20.8 months), respectively. In patients who had interval debulking surgery, the median overall survival was 57.9 months (95% CI 43.2 to 72.7 months) in those with complete cytoreduction, 33.4 months (95% CI 25.0 to 41.7 months) for those with optimal cytoreduction and 28.4 months (95% CI 21.6 to 35.2 months) for those with suboptimal cytoreduction (Phillips 2019).

A Cochrane systematic review, including 3 studies, concluded that survival may be prolonged in woman who had ultra-radical surgery compared to standard surgery but the evidence was limited and very uncertain: HR 0.60 (95% CI 0.43 to 0.82); 2 studies, n=397 (Hiu 2022).

Progression-free survival

In the cohort study of 247 patients, progression-free survival at 2 years was 34% (95% CI 24.7 to 42.3%) in patients in the low SCS group, 47% (95% CI 35.0 to 58.6%) in the intermediate SCS group and 34% (95% CI 22.4 to 46%) in the high SCS group (p=0.109). For patients with no residual disease, progression-free survival at 2 years was 47% compared with 21% (p<0.001) for those with residual disease (Sundar 2022).

In the retrospective analysis of chemotherapy trials of 2,655 patients, median progression-free survival was 18.5 months in those who had low SCS surgery, 18.0 months in those who had moderate SCS surgery and 14.9 months in those who had high SCS surgery (p<0.01). For patients with complete resection, median progression-free survival was 28.9 months compared with 15.3 months (p<0.01) for those with residual disease (Horowitz 2015).

In the cohort study of 978 patients with advanced ovarian cancer who had primary debulking surgery, 5-year progression-free survival was 15% in those who were treated between 2001 and 2005, 16% in those who were treated between 2006 and 2009 and 20% for those who were treated between 2010 and 2013 (p=0.199; Tseng 2018).

In a cohort study of 384 patients with stage 3 or 4 ovarian cancer who had primary or interval debulking surgery, median progression-free survival was 17.2 months (95% CI 15.2 to 20.7 months) in the low SCS group compared with 21.5 months (95% CI 18.2 to 25.7 months) in the intermediate or high SCS group (p=0.038; Palmqvist 2022).

The Cochrane systematic review concluded that disease progression may be delayed in women who had ultra-radical surgery compared to standard surgery but the evidence was limited and very uncertain: HR 0.62 (95% CI 0.42 to 0.92); 1 study, n=203 (Hiu 2022).

Completeness of resection

In the population-based cohort study of 3,728 patients, the proportion of patients with no residual tumour after primary debulking surgery increased from 29% (224/968) to 53% (430/835) after the implementation of national guidelines (Dahm Kahler 2021).

In the cohort study of 247 patients, complete macroscopic tumour clearance was reported in 56% (63/113) of patients in the low SCS group, 71% (50/70) of patients in the intermediate SCS group and 63% (40/64) in the high SCS group (p=0.007; Sundar 2022). In the cohort study of 752 patients, the complete resection rate increased from 37% to 67% (p≤0.001) after the shift to upfront and ultra-radical surgery (Falconer 2020).

In the retrospective study of chemotherapy trials of 2,655 patients, those who had high SCS surgery were statistically significantly more likely to have complete resection than those who had low SCS (OR 4.17, 95% CI 2.30 to 7.56; p<0.01) or moderate SCS surgery (OR 2.66, 95% CI 1.91 to 3.70; p<0.01; Horowitz 2015).

In the cohort study of 978 patients with advanced ovarian cancer who had primary debulking surgery, the rate of complete gross resection was 29% in those who were treated between 2001 and 2005, 40% in those who were treated between 2006 and 2009 and 55% for those who were treated between 2010 and 2013 (p<0.001; Tseng 2018).

In the cohort study of 608 patients, complete cytoreduction rates were statistically significantly higher (87.7% compared with 56.7%, p<0.0001) in patients who had ultra-radical surgery compared with those who had standard surgery (Phillips 2019).

In the cohort study of 384 patients, the rate of complete cytoreduction was 48.7% (187/384; Palmqvist 2022).