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\title{Important insights for non-molar choriocarcinoma. (Mini-commentary on
BJOG-19-1824.R1)}



\author[1]{Neil Horowitz}%
\author[2]{Ross Berkowitz}%
\author[2]{Kevin Elias}%
\affil[1]{BWH}%
\affil[2]{Brigham and Women's Hospital Department of Obstetrics and Gynecology}%


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  \date{June 13, 2024}


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Mini-commentary on BJOG-19-1824.R1: Demographics, Natural History and
Treatment Outcomes of Non-Molar Gestational Choriocarcinoma; A UK
population study

\textbf{Important insights for non-molar choriocarcinoma}

Neil S. Horowitz,*\textsuperscript{1} Ross S.
Berkowitz,\textsuperscript{1} and Kevin M. Elias\textsuperscript{1}

\textsuperscript{1} New England Trophoblastic Disease Center, Division
of Gynecologic Oncology, Department of Obstetrics and Gynecology,
Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard
Medical School, Boston, MA, 02115, USA.

* Email: nhorowitz@partners.org

Although gestational trophoblastic neoplasia (GTN) is a rare event,
particularly after a non-molar pregnancy, the true incidence of GTN is
difficult to establish with certainty because data regarding the
incidence of pregnancies and subsequent trophoblastic events are not
available in most countries. This is not the case in the United Kingdom,
where there is nearly a 50-year history of unified care of GTN at two
major reference centres. The data generated from these centres has
positioned them as world leaders in the care of women with GTN. In
conjunction with national statistics on conceptions and birth, this data
enabled the authors the unprecedented ability to estimate the incidence
of non-molar choriocarcinoma. Furthermore, these reference centres had
access to more granular demographic, clinical and cancer related data,
not previously available in other studies, thus providing a more
insightful understanding of non-molar choriocarcinoma.

In the current manuscript, the authors estimate that the incidence of
non-molar choriocarcinoma was 1 in 66,775 births or 1 in 84,226
conceptions (BJOG 2020 xxxx). This is similar to other estimates and
confirms the rarity of this disease (Hextan NYS Int J Gynecol Obstet
2018;143 (Suppl2):79-85). Approximately two-thirds of these cases
(65.4\%) presented after a term pregnancy and nearly 25\% presented more
than a year after the antecedent pregnancy. This delay in diagnosis is
not surprising. Unlike hydatidiform moles that in the UK are mostly
evacuated in the first trimester and followed with weekly hCG to allow
early detection of persistent tumor requiring chemotherapy, term
delivery and therapeutic abortions typically are not followed with
serial hCG. GTN in these cases is only diagnosed when symptoms, like
irregular bleeding, arise and when astute clinicians consider a very
rare diagnosis. Given this delayed diagnosis, metastases were common
with nearly 45\% of women presenting with FIGO high-risk and 20\% with
ultra high-risk disease. Whether this reflects the biology of non-molar
choriocarcinoma or whether it relates to duration of disease prior to
diagnosis is not clear. Despite these risks, the overall cure rate was
high, 100, 96 and 80.5\% for low-risk, high-risk and ultra high-risk,
respectively.

An important observation reinforced by this manuscript is the
association of maternal age as a risk factor for GTN. Whether one
considers the incidence of hydatidiform mole, the rate of postmolar GTN
requiring chemotherapy, or non-molar choriocarcinoma, advanced maternal
age is associated with increasing risks (Elias KM et al. J Reprod Med
2012;57:354-8). Though one could speculate why there is this association
with maternal age, (diminished immune surveillance, age-related changes
to the microenvironment, etc.) the exact mechanism is not fully
understood. This information can be useful however when considering
non-molar choriocarcinoma in the differential of those with advanced
maternal age who present with irregular bleeding postpartum or
post-abortion.

Gaining insight into the incidence, natural history, and clinical
outcomes of non-molar choriocarcinoma is a critical addition to the
literature that will improve the counseling and care of women with this
disease. For this, the authors should be congratulated.

\textbf{No disclosures:} Completed disclosure of interest forms are
available to view online as supporting information.

\textbf{Funding:} The authors acknowledge support from the Donald P.
Goldstein MD Trophoblastic Tumor Registry Endowment and the Dyett Family
Trophoblastic Disease Research and Registry Endowment.

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