Prenatal cell-free DNA testing of women with pregnancy-associated cancer: a retrospective cross-sectional study

Abstract

Background: Incidentally, the non-invasive prenatal test (NIPT) shows chromosomal aberrations suspicious of a maternal malignancy, especially after genome-wide testing. The aim of this study is to determine how many cases of cancer in pregnancy are diagnosed or missed with NIPT and whether in retrospect subtle changes in NIPT results could have detected cancer.

Methods: We identified Dutch patients diagnosed in 2017-2021 with pregnancy-associated cancer from the International Network on Cancer, Infertility and Pregnancy (INCIP) Registry, who underwent NIPT in the Dutch NIPT implementation study (TRIDENT-2). We retrospectively assessed how many of these women showed a malignancy suspicious-NIPT, their tumour types and -stages, and the time interval between NIPT and cancer diagnosis.

Findings: Of 143 women with pregnancy-associated cancer, we included 65 patients that underwent an NIPT. Fifty-four women had a solid tumour and 11 a haematological malignancy. Sixteen (24.6%) NIPTs were malignancy suspicious (15 genome-wide, one targeted). All 10 haematological cancer patients with genome-wide NIPT had a malignancy suspicious-NIPT, irrespective of the disease stage. Only five patients with a solid tumour had a genome-wide malignancy suspicious-NIPT (4/5 advanced cancer stage III or IV). The mean time between date of NIPT and cancer diagnosis was significantly shorter after a malignancy suspicious-NIPT compared to a non-suspicious-NIPT, respectively 49.9 days (± SD 31.8) and 100.7 days (± SD 74.9), p = 0.001.

Interpretation: All genome-wide NIPT in women with pregnancy-associated haematological malignancies were malignancy suspicious. Women with a solid tumour showed a malignancy suspicious-NIPT in only a minority of cases, mainly the advanced stages.

Funding: None.

Keywords: Noninvasive prenatal test; Pregnancy-associated cancer.

Fig. 1

Study population. The number of Dutch patients included in the INCIP study in the study period (n = 143), and the number of patients who had undergone an NIPT within the TRIDENT-2 study. In the TRIDENT-2 study 334499 NIPTs were performed between April 1 2017 and April 1 2021. aReviewed NIPT result according to the “Maastricht criteria”. Abbreviations: INCIP: International Network on Cancer, Infertility and Pregnancy. NIPT: non-invasive prenatal test. TRIDENT: Trials by Dutch Laboratories for Evaluation of Non-Invasive Prenatal Testing.

Fig. 2

a) NIPT results for the haematological malignancies (n = 11) per Ann Arbor tumour stage at diagnosis. The y-axis represents the number of patients and the x-axis represents the different tumour stages divided into genome-wide (solid bars) and targeted (shaded bar) NIPT. The colours represent the reviewed NIPT results. Genome-wide NIPT was able to raise strong suspicion (orange bars) for all 10 haematological malignancies of all stages during pregnancy, whereas one postpartum diagnosed malignancy was tested normal with targeted NIPT (shaded green bar). See also Supplemental Table S2. Abbreviations: NIPT: Non-invasive prenatal test. b) NIPT results for the solid tumours (n = 54) per tumour stage at diagnosis using the TNM-, FIGO- or WHO classification. The y-axis represent the number of patients and the x-axis the different tumour stages divided into genome-wide (solid bars, n = 43) and targeted (shaded bars, n = 11) NIPT. The colours represent the reviewed NIPT results. NIPT was able to raise suspicion for malignancy only for 6 of 54 solid tumours, 5 of 43 with genome-wide NIPT and 1 of 11 with targeted NIPT. For solid tumours with stage I and II only 1 of 30 genome-wide NIPT results showed suspicion for a malignancy, see also Supplemental Table S2. Abbreviations: NIPT: Non-invasive prenatal test.

Fig. 3

Time between NIPT and the cancer diagnosis. This figure shows the time in days between the blood draw for NIPT (t = 0) and the diagnosis of cancer. Time is plotted on the y-axis and on the x-axis the subgroups of patients with respectively a non-suspicious NIPT result (n = 48), and suspicious-NIPT result (n = 14). The number of NIPT results for genome-wide and targeted NIPT were taken together. The dotted line represents the connection of the mean. One patient, NIPT-18 (non-suspicious NIPT), was excluded in this analysis because the actual date of disease recurrence was not known to us. The time to cancer diagnosis was set on zero for the three patients with a cancer diagnosis within one week before NIPT. The asterisks denote the outliers.