The annual incidence rate of cancer is estimated to be more than 11,000 patients in the U.K. in the age group of 15–40 years, which corresponds to 4% of all cancer patients. The diagnosis of cancer is followed by devastating consequences for the patients and their families in this age group. Although the treatment of cancer is of crucial significance, it should also examine the impact of the disease on fertility at the time of the diagnosis and the damages caused from the surgical treatment, chemotherapy, or radiotherapy. The gynecological cancer, especially the diagnosis of ovarian cancer, the prevention, and treatment, as well as the fertility preservation in young women, represent the gold standard for all gynecologists. The crucial disadvantage remains the difficulty in primary diagnosis of ovarian cancer and the coexistence with pregnancy, focusing on the fertility preservation and maintaining pregnancy. In the absence of large perspective randomized trials and cohort studies, the therapeutic mapping and optimal management of these patients are difficult. In order to establish detailed guidelines, it is necessary to ensure surgical mapping depending on the cancer staging and the quality of life of the patients.
- ovarian cancer
- fertility preservation
The presence of adnexal masses during pregnancy consists of a less rare condition. With the help and increase of the transvaginal ultrasound, the diagnosis of adnexal masses or cysts becomes more frequent. The incidence of these masses during pregnancy is estimated to be 0.2–2% depending on the week of gestation. The malignancy rate consisted of 1–6%, leaving the vast majority in benign level .
Distinguishing between malignant and nonmalignant adnexal masses or cysts especially during pregnancy depends on the level experience of the gynecologist and the disease staging. The most common nonmalignant cyst represents the functional cysts. These cysts or presence of corpus luteum are harmonically influenced and depict different ultrasound morphology. Imaging findings consist of thin wall without disturbance of architecture and lack of vascularization (Figure 1) .
These functional cysts can be shortly or after a couple of months absorbed. The appearance of adnexal mass or cyst during early pregnancy must lead to differential diagnosis of an ectopic pregnancy. Other examples such as cystadenomas or dermoid cysts during pregnancy can be removed laparoscopically during the first trimester.
The evaluation of an adnexal mass and the differential diagnosis toward a possible adnexal malignancy can be managed with ultrasound examination, abdominal MRI, and tumor markers.
Ultrasound examination can easily be undergone and consists of routine procedure with increased sensitivity and specificity, respectively. Imaging findings can facilitate the differential diagnosis between a malignant and a benign adnexal disease.
The mentioned ultrasound imaging clearly depicts the presence of color Doppler as indirect sign of malignant vascularization, presence of papillary protrusions inside the adnexal wall, and disturbance of adnexal architecture. All these ultrasound characteristics indicate the presence of ovarian cancer .
The use of MRI safely during second or third trimester of gestation increases, accompanied with the ultrasound imaging findings, the sensitivity and specificity of diagnosing ovarian cancer during pregnancy. Diagnostic keys during abdominal MRI can be tumor invasion or spread, lymphatic spread, disease staging, and possible metastatic lesions .
The use of tumor markers in cases of adnexal masses or cysts often accompanied with pregnancy remains a controversial entity. Due to daily physiologic and hormonal changes during pregnancy, all tumor markers are increased. Ca-125, a tumor marker capable of distinguishing a benign from a malignant adnexal mass, is often increased during pregnancy .
Other tumor markers, such as alpha fetoprotein (AFP) and b-HCG often increased in germ cell tumors or Inhibine B and anti-mullerein protein (AMH) often increased in granulosa-associated tumors, are equally increased during all trimesters of gestation .
Additionally, elevated Ca-125 levels were found in cases of acute pelvic inflammatory disease (PID). Many current studies have been conducted assuming the presence of the mentioned tumor marker in the fallopian tubes .
Generally, tumor markers are not used as a screening test. From their point of view, they contribute indirectly toward the final diagnosis. The therapeutic mapping consists of the assiduous physical examination, the imaging findings, and the ranges of the laboratory examination. Ultimate goal remains the quality of life regarding the mother and the fetus.
According to current literature and long conductive series, the frequency of adnexal masses during pregnancy is estimated to be 1 in 81 to 1 in 2500 live births .
The therapeutic mapping regarding the presence of ovarian carcinoma depends on the predisposition factors, such as the tumor size, tumor staging, lymphatic infiltration, tumor invasion, and presence of metastatic lesions such as liver, brain, and bone metastasis.
The ultimate goal remains the cytoreduction or better debulking. In other words, peritoneal washing, total hysterectomy, bilateral salpigoopherectomy, pelvic and paraortic lymph node dissection, inspection of all peritoneal surfaces and multiple biopsies, and finally, omentum dissection.
There are nonspecific clinical signs to primarily diagnose the existence of ovarian cancer (Figure 5).
The most significant issue remains the therapeutic mapping regarding the combination of ovarian cancer and pregnancy.
As we mentioned above, primary goal represents the increase of free survival rate and quality of life of the mother and fetus, respectively (Figure 7).
The incidence of ovarian cancer is increased in older pregnant women . In other words, age represents a predispositional factor which influences the pregnancy outcome.
Many studies from the current literature suggested that many histologic types of ovarian cancer in pregnant women are similar to those in nonpregnant women . Surgical dissection of an adnexal mass diagnosed during pregnancy remains a controversial issue. Adnexal mass with diameter larger than 6 cm, with peripheral vascularization, ascites, or persistent presence of more than 4 months, requires surgical dissection and histologic confirmation and exclusion of potential malignancy .
Generally, the ultimate treatment of ovarian cancer during pregnancy consists of surgical intervention with adequate staging. For advanced stages, stages with metastatic lesions, the current literature, and the standard guidelines recommend treatment similar to nonpregnant women—surgical debulking combined with series of chemotherapy or radiotherapy (Figure 8).
As we mentioned above, the standard treatment of epithelial ovarian cancer (EOC), the histologic type with the worst prognosis, consists of total hysterectomy, bilateral salpigoopherectomy, peritoneal washing, dissection of the omentum, dissection of all peritoneal implants, and most of all lymph node dissection (pelvic and paraaortic).
If all imaging findings and the laboratory report advocate of an early-stage lesion, the therapeutic mapping is focusing on unilateral oophorectomy or adnexectomy with appropriate staging. It is very important to keep in mind all conservative surgical methods focusing on the pregnancy maintenance.
In cases of advanced stages, termination of pregnancy and use of noeadjuvant chemotherapy or radiotherapy is recommended.
When series of chemotherapy are mandatory regarding advanced stages of ovarian cancer, the suitable period is during the second or third trimester, avoiding the organogenesis of first trimester, period with increased incidence of genital malformations. During these trimesters, the risk of genital malformations does not exceed the risk of general population .
Additionally, for patients with diagnosed ovarian cancer during pregnancy and focusing on the current guidelines platinum-based chemotherapy, combination of carboplatin with weekly paclitaxel is strongly recommended after the first trimester, representing a safe chemotherapeutic procedure .
Radiotherapy is recommended in advanced stages alone or in combination with series of chemotherapy. The current literature and the global guidelines strongly advise doses of radiotherapy as in nonpregnant women.
Radiotherapy is restricted in cases of dysgerminoma as an example of the most common germ cell tumor due to its radiosensitivity. The field of exposure extends from T11 to L5, with shielding of the contralateral ovary and the femur head .
Therapeutic mapping of ovarian cancer during pregnancy remains a controversial issue. Many studies have been conducted in order to establish safe guidelines of treatment with the ultimate goal of increasing free survival and quality of life of the mother and the fetus. Primary diagnosis, multidisciplinary cooperation, assiduous imaging findings, and laboratory examinations assure proper treatment.
Disclosure of interest
The author declares no financial interest with respect to this manuscript.