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5.1.3 Summary of available scientific evidence LoE 1-
Primary cytoreductive surgery: using the technique of meta-analysis, Elattar et al.127 and Chang et
al.128 quantified the effect on survival of surgical outcome criteria among patients with advanced-
stage ovarian cancer. Eleven studies129-152 and 18 studies3,130,136,139,142,144-149,151,153-158 were included in
these meta-analyses, respectively. Six studies130,136,139,142,144-149,151 were included in the 2 meta-
analyses.
Elattar et al.127 assessed the impact of various residual tumour sizes on survival. A subgroup meta-
analysis of 4 studies136-139,142,144-150, showed that women who were suboptimally debulked resi dual
disease > 1 cm after primary cytoreductive surgery had more than 3 times the risk of death
compared to women with only microscopic disease HR = 3.16, 95% CI = 2.26 -4.41, p < 0.05. An
another subgroup meta-analysis of 6 studies130-133,136-139,142,144-152, showed that women who were
optimally debulked residual disease < 1 cm after primary cytoreductive surgery had more than
twice the risk of death compared to women with only microscopic disease HR = 2.20, 95% CI =
1.90-2.54, p < 0.05. The authors reported that compl ete resection no visible residual disease is also
associated with prolonged PFS compared to optimal resection 2 studies 144-152, HR = 1.96, 95% CI =
1.72-2.23, p < 0.05.
Chang et al.128 performed separate multiple linear regression analyses using no gross residual disease
or optimal residual disease ≤ 1 cm as the surgical outcome criteria. Although both criteria were
significant and independent predictors of improved cohort survival after ajustement for stage and use
of intraperitoneal chemotherapy, each 10% increase in the proportion of patients undergoing
complete gross resection was associated with a 28% incremental improvement in the expected
median survival time 2.3 months, 95% CI = 0.6 -4.0, p = 0.011 compared to the proportion of
patients left with optimal residual disease 1.8 month, 95% CI = 0.6 -3.0, p = 0.004.
Twenty-six original studies159-184 not included in the 2 meta-analyses mentioned above were also LoE 2-
identified. All studies reported a significant benefit on survival to achieving an optimal
cytoreduction. Twenty-three studies analyzed the independent prognostic value of optimal
cytoreduction on OS or progression-free survival PFS using 3 optimal surgery criteria no gross, <1
cm and ≤1 cm. Multivariate analyses showed that optimal cytoreductive surgery was found to be
independently prognostic for OS in 17 of 19 studies and in all studies N = 10 for PFS Table 1.
According to data released by Everett et al.176, Aletti et al.177 and Kumpulainen et al.178, optimal
primary cytoreductive surgery is also a statistically independent prognostic factor for progression-
free interval ≤1 cm 176, disease-specific OS <1 cm 177, disesase-specific survival no gross 184 and
disease-free survival ≤1 cm 178.
Delayed cytoreductive surgery: as part of a meta-regression analysis185 including 21 studies176,186-204, LoE 1-
an increased rate of optimal cytoreduction significantly influenced median OS coeff. = 0.013, 95%
CI = 0.003-0.023, p = 0.012. It should be noted that the results published by Kang et al.185 have to
be interpreted cautiously notably because there is severe heterogeneity between the included studies.
Four original studies158,184,205,206 not included in the meta-analysis mentioned above were also LoE 2-
identified. The four studies reported a significant benefit on survival to achieving an optimal
cytoreduction. According to data released by three original studies184,205,206, optimal delayed
cytoreductive surgery surgery criteria: no gross, <1 cm and ≤1 cm is a statistically independent
prognostic factor for OS, PFS, and DSS Table 2.
It should be noted that the available evidence presented above has to be interpreted cautiously
notably because 1 a potential interobserver bias in assessing the diameter of residual disease may
influence the results, 2 a limitation of the identified studies is that they were largely confined to
younger women and those with a good performance status and the results might therefore not be
generalisable to the wider patient population, and 3 the exact reasons for performing one type of
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