Why did early screening not reduce ovarian cancer mortality?

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Why did early screening not reduce ovarian cancer mortality?

Why did early screening not reduce ovarian cancer mortality?  Is ovarian cancer screening really “useless”? What is the current status of ovarian cancer treatment? Let’s take a look!

Ovarian cancer has always been the “invisible killer” for women-patients with early ovarian cancer have unobvious signs and lack of effective screening methods, and more than 70% of patients are at an advanced stage when they are diagnosed.

Is the early screening of ovarian cancer really a drop in the bucket? Has the neoadjuvant therapy, which has become more popular in recent years, already help doctors? What hope can the increasingly mature targeted therapy bring to patients with ovarian cancer?

Many people now think that screening for ovarian cancer has little effect. What are their views on the prevention and screening of ovarian cancer?

Transvaginal ultrasound screening and ovarian cancer screening for biomarkers such as CA125 have been in progress, but this type of screening has been clinically proven to have limited effect on most ovarian cancer patients, and most studies have also concluded similar The conclusion.

The results of the recent UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) were published in the journal Lancet. The 16-year follow-up results of the study showed that compared with women who did not receive ovarian cancer screening, they received multimodal screening (including ovarian cancer risk algorithm, serum CA125 repeat testing, transvaginal ultrasound screening) and simply received transvaginal ultrasound screening The women examined did not reduce their ovarian cancer mortality, and early diagnosis and timely treatment did not seem to change the poor prognosis of ovarian cancer (Figure 2) [1].

Figure 2: Kaplan-Meier curve shows the cumulative mortality of ovarian cancer and fallopian tube cancer per 100,000 women

Nevertheless, clinical screening for ovarian cancer cannot be given up. First of all, it is worth noting that not all patients with ovarian cancer cannot benefit from early screening. Although only about 20% of ovarian cancer patients have genetic related factors, it is very necessary to screen such patients.

Epidemiological data show that women without germline BRCA gene mutations have a 1%-2% chance of developing ovarian cancer, while women with BRCA gene mutations have a greatly increased risk of ovarian cancer. Therefore, BRCA gene testing should be performed on high-risk populations. Very important. Genetic testing can not only clarify the system, germline BRCA gene mutation and homologous recombination repair gene status, but also provide a basis for the use of PARP inhibitors. The high-risk groups of ovarian cancer mainly include:

• There is a BRCA1/2 mutation in the family;
• Have a history of ovarian cancer or other hereditary breast/ovarian cancer syndrome (HBOC) related tumors, and the age of diagnosis is ≤50 years;
• Suffer from HBOC-related tumors, and the age of diagnosis is ≤60 years old, and has a second primary tumor, or triple-negative breast cancer, or ≥1 close relatives have HBOC-related tumors;
• ≥2 people in close relatives suffer from HBOC-related tumors;
• A close relative of a male has breast cancer;
• The BRCA1/2 mutation was detected in the tumor tissue, but germline analysis was not performed.

For these high-risk women, it is clinically recommended to have CA125 and ultrasound examinations every six months from the age of 30, and preventive ovarian and fallopian tube resection can also be considered.

In addition, in recent years, the application of circulating tumor DNA, DNA methylation and autoantibodies and other biomarkers has also been gradually explored, and it is expected to be a new method for early screening of ovarian cancer in the future.

What is the current status of targeted therapy for ovarian cancer in recent years? What are the new targets that can be applied to ovarian cancer?

Drugs related to targeted therapy can be described as blooming. As an anti-angiogenic drug that has been on the market for many years, bevacizumab is undoubtedly an important part of targeted therapy for ovarian cancer; in addition, PARP inhibitors such as olaparib are also increasingly used as ovarian cancer Means of maintenance therapy; immunotherapy represented by PD-1 inhibitors and PD-L1 inhibitors actually also belongs to the category of targeted therapy, and currently clinical research is also being carried out.

In addition to these well-known targets, the antibody-conjugated drug Mirvetuximab Soravtansine (MIRV) that targets folate receptor α (FRα) mentioned in the FORWARD II study selected by the BOA conference is also an attempt for new targets.

The study included a total of 60 patients receiving MIRV+bevacizumab combination therapy, including 32 platinum-resistant ovarian cancer patients (53%) and 28 platinum-sensitive ovarian cancer patients (47%). The median age was 60 years, the median number of treatment lines was 2, and the median follow-up time was 17.5 months.

The results showed that 28 of the 60 patients had objective remission, with an objective remission rate (ORR) of 47%, a median duration of remission (DOR) of 9.7 months, and a median progression-free survival (PFS) of 8.3 month. Among patients with high FRα expression (n=33), ORR was 64%, DOR was 11.8 months, and PFS was 10.6 months [2].

Table 1: FORWARD II study results

MIRV combined with bevacizumab has strong anti-tumor activity and tolerance in recurrent ovarian cancer with high FRα expression. Therefore, for recurrent ovarian cancer, regardless of the sensitivity of platinum drugs, MIRV+bevacizumab has the potential to become the first choice for patients with recurrent ovarian cancer with high FRα expression.

With further research on the molecular classification of tumors, many other new targets have actually been discovered clinically, but whether these new targets have clinical value and whether they can be transformed into clinical benefits for patients needs further research. To confirm.

What is the current status of neoadjuvant therapy for ovarian cancer?

In the treatment of ovarian cancer, clinicians used to perform pre-surgery chemotherapy, which is neoadjuvant chemotherapy, mainly for patients who were unwilling or unable to undergo surgery during the initial treatment.

For newly diagnosed patients with ovarian cancer, clinicians will first perform clinical analysis on them to determine whether they can be operated directly. If surgery cannot be performed directly, clinicians will consider neoadjuvant treatment-about 70% of patients with ovarian cancer in the clinic are already stage II or III ovarian cancer at the first diagnosis, and they are in the middle and advanced stages. If you directly treat these patients It is difficult to achieve R0 resection (complete resection) during surgery. The purpose of neoadjuvant therapy is mainly to achieve tumor shrinkage, so that subsequent surgery can achieve R0.

Before neoadjuvant therapy, clinicians will also assess whether the patient is suitable for neoadjuvant chemotherapy, and there are now more accurate criteria for judging it. Among them, CT imaging score is to judge the extent of tumor spread in the upper abdomen through preoperative imaging examination, according to the spleen hilum, hepatic hilum, gallbladder fossa, liver parenchyma, diaphragm and other parts of the metastasis, as well as the clinical characteristics of the patient. If the imaging score is greater than or equal to 3 points, neoadjuvant chemotherapy is recommended; in addition, the Fagotti endoscopic score is a laparoscopy to explore which parts of the abdominal cavity tumors have expanded, and whether the tumors in these parts can be completely removed for endoscopic score, 8 points and The above patients are recommended to undergo neoadjuvant chemotherapy before surgery.

Although there have been controversies about the appropriateness of neoadjuvant chemotherapy-many clinicians believe that neoadjuvant chemotherapy will cause chemotherapy resistance, and that neoadjuvant chemotherapy alone cannot completely solve the problem, surgery still needs to be performed. However, in recent years, neoadjuvant chemotherapy has been proven beneficial in large-scale clinical trials and has become an important part of the treatment of ovarian cancer.

The current exploration direction of neoadjuvant therapy is to use other drugs instead of chemotherapeutic drugs for neoadjuvant therapy. For example, clinically, we are trying to use targeted drugs such as PARP inhibitors to replace chemotherapy drugs. In addition, clinically referenced studies for patients with different subdivisions are also being carried out, which is expected to bring optimization and improvement to neoadjuvant treatment strategies for ovarian cancer in the future.

(source:internet, reference only)

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