4.3 Interpretation
The oncological safety of IU manipulators in endometrial cancer remains
a subject of debate. Although previous studies did not specifically
compare IU with non-IU manipulators, our findings support earlier
research in a homogenous population with low risk EEC
patients12–14,23–25. A recent meta-analysis by
Scutiero et al. demonstrated that the use of IU manipulators did not
impact the recurrence rate compared to when no manipulators were used in
TLH for clinically early-stage endometrial cancer (risk ratio [RR]
1.11, 95% CI 0.71–1.74)13. Furthermore, Uccella et
al. found no association between different IU manipulators used and the
risk of recurrence. Additionally, no difference in recurrence pattern,
DFS, and OS between the use and non-use of manipulators during TLH were
observed24. In line with this, Alletti et al.
illustrated similar DFS and OS after TLH with and without IU manipulator
in a multicentric randomized controlled trial14.
On the contrary, several research groups have indicated that the use of
IU manipulators negatively affects oncological
outcome15,16. Padilla-Iserte et al. showed that the
recurrence rate (HR 2.31, 95% CI 1.27–4.20) and survival were worse
after TLH with IU manipulator than without manipulator, but no
difference in recurrence pattern was found. Interestingly, the decrease
in DFS and OS was only observed in patients with FIGO I-II endometrial
cancer (HR 0.74, 95% CI 0.57–0.97 vs HR 1.74, 95% CI 1.07–2.83,
respectively) and not in those with FIGO III endometrial
cancer15.
In our cohort, the positive LVSI rate was significantly higher in the IU
group (12.7%) than in the non-IU group (10.5%), but no correlation was
observed with worse survival. LVSI and PPC have both been considered
poor prognostic factors for recurrence and survival in endometrial
cancer. However, it remains disputable whether these factors are
associated with the use of uterine manipulators7–11.
Scutiero et al. reported that there were no differences in LVSI and PPC
rate between the use and non-use of IU manipulators during TLH.
Moreover, the incidence of PPC before and after insertion of the IU
manipulator was similar, which suggested that the use of IU manipulators
was not associated with PPC conversion13. In
disagreement with these findings, Siegenthaler et al. showed that
laparoscopy with IU manipulation was followed by PPC conversion in 8.1%
of patients, which was significantly associated with higher recurrence
rate and lower DFS and OS. In their study, peritoneal washings were
taken at three time points: at the beginning of surgery, after
manipulator insertion, and after vaginal vault closure. They found that
80% of cytology conversions occurred at the third washing, implying
that the presence of the manipulator in the uterine cavity during the
whole procedure is the main issue, rather than the insertion of the
manipulator itself16. Interestingly, hysteroscopy has
been associated with higher PPC rates, but without worse oncological
outcome26–29. This discrepancy might result from
different ways of handling the IU device. During hysterectomy, the IU
manipulator is in theory more likely to induce trauma, which might lead
to cancer recurrence by disrupting the containment barrier, whereas
hysteroscopy involves passively rinsing out tumour
cells16. Our observation of no significant differences
in site of recurrence argues against this theory.
One explanation for the contrasting results observed across studies is
the small sample size of the majority of research, combined with the low
recurrence rate in endometrial cancer14,23,25.
Although studies with small sample sizes should not be disregarded,
their results are limited in statistical power. In addition, the
variation in follow-up duration between studies, ranging from
1925 to 120 months16, contributes to
the inconsistency in earlier findings, as time is important when
evaluating oncological outcomes. Furthermore, most studies included a
heterogeneous population of patients in terms of tumour stage, grade,
and histotype15,16,23–25. Alletti et al. was the only
study that specifically focused on clinically early-stage, low-grade EEC
patients, but only included 154 patients14. Another
contributing factor could be the different manipulators used during
surgery12,13. Since favourable and adverse effects of
tumour manipulation may be affected by the type of manipulator,
potential manipulator-specific differences should be considered.
Moreover, the overall recurrence in our study was 3.7%, which is lower
than the 9.7% reported by Reijntjes et al. in the same low-risk
population30. This suggests a relative underreporting
of recurrence in our data. One explanation is that we defined recurrence
as histologically confirmed recurrence according to PALGA, leading to
some patients with not-histologically confirmed recurrences being missed
in our study. Although NCR has not systematically recorded cancer
recurrence, NCR has documented recurrence data between 2015 and 2017 in
a pilot study. By comparing the NCR pilot data to the PALGA data, we
established that the number of missed recurrences was similar between
the IU and non-IU group in this period.