Classification of cervical cancer

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Cervical cancer is one of the most common malignant diseases of women. This is the most common tumor among women of reproductive age. When one has cancer of the cervix, metastases appear early and it can cause a large number of negative outcomes. If it is the second stage of the pathology, there is a great possibility for one's death. Good results of treatment can only be achieved when patients are at 0 or 1 stages of cervical cancer. However, even if the stage 4 is mentioned in the diagnosis, efficient treatment options are available. In this article we will discuss everything from determining the stage of the disease to assessing the cost of treatment for cancer stage 4.

Content

1. What types of diseases are there in general?
2. Stages of development of cervical cancer
   • Cervical cancer 0 stage
   • Cervical cancer stage 1
   • Cervical cancer stage 2
   • Cancer of the cervix at the stage 3
   • Cervical cancer stage 4
3. Distribution of metastases at different stages of the cervical cancer
4. Peculiarities and costs of stage 4 cervical cancer treatment options
5. Treatment in Germany

What types of diseases are there in general?

There are two main types of malignant tumors, which can develop from the cervix - squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma of the cervix is ​​the most common one. The proportion of squamous cell carcinoma of the cervix in the general takes 85 %, whereas adenocarcinoma stands on the second place and takes 10-15%. Other histological types of cervical cancer in gynecology occur rarely.

Those include:

• Small cell carcinoma
• A neuroendocrine tumor
• Undifferentiated carcinoma

There are the following types of the squamous cell carcinoma of the cervix:

• Non-keratinizing squamous cell carcinoma of the cervix
• Keratinizing squamous cell carcinoma of the cervix
• Invasive squamous cell carcinoma of the cervix
• Verrucous carcinoma of the cervix

One distinguishes tumors according to the degree of differentiation of the cells from which they develop. Low-differentiated squamous cell carcinoma of the cervix and moderately differentiated squamous cell carcinoma of the cervix are rare. The major part of the neoplasms is highly differentiated.

Besides, there are two forms of the tumor according to the growth pattern:

• Exophytic cancer growing in the lumen of the cervical canal
• Endophytic tumor growing towards the wall of the organ, gradually infiltrating it (less favorable in the prognostic plan, and more common form)

These are the main types of cervical cancer. But the most important thing during the prognosis is the stage of oncology, not the histological type or growth type.  Therapeutic tactics and life expectancy of a patient depend on the  following factors: the size of a neoplasm, growing into surrounding tissues and the existence of the metastases. Therefore, in cervical cancer, the classification is based primarily on the definition of the oncological stage.

Stages of development of cervical cancer

Unlike most malignant neoplasms, in cervical cancer, stages are determined mainly based on the characteristics of the primary tumor. During the diagnostics the doctors rarely take into account the presence of metastases in the lymph nodes.

For cervical cancer, the clinical stage is based on the results of the doctor's examination. In the future, the stage of cervical cancer can not be changed.

Sometimes there can appear some new data during additional examination or during the surgery. In this case, the treatment plan can be changed. But the stage of the oncological process will still remain the same. It will not change over time if the tumor develops, and the primary neoplasm will increase significantly in size. Thus, the initial diagnostics remains crucial.

Currently, two staging systems are used - FIGO and TNM. There is no big difference between them, the stages can be designated differently.

Cervical cancer 0 stage

Initial stage of cervical cancer can be detected only when a woman regularly visits a gynecologist. It is called "cancer in place" (cervix cancer "in situ"). The average age of patients with this disease is 30-35 years. In 10-15 years this type of cancer will change into the invasive carcinoma. Despite this fact, the tumor is rarely diagnosed at this stage.

Neoplasm does not appear suddenly. The onset of cancer is preceded by long-term pathological processes taking place within the cervix. Initially, cervical intraepithelial neoplasia develops 1 degree, then 2 and 3 degrees. Even with the detection of severe dysplasia, it is possible to perform surgical treatment and to prevent the development of oncological formation. If this does not happen, initial stage of cervical cancer will develop approximately in 3 years. In this phase of development, the tumor has no metastases and is limited in the uterine mucosa. It can be removed completely.

In order to do this, one uses the following methods:

• Cryosurgery
• Laser surgery
• Electrosurgical removal
• Conization of the cervix
• Hysterectomy (removal of the uterus)

The choice of the method depends on the histological form of the neoplasm. If it is squamous cell carcinoma of the cervix, its prognosis is more favorable. In this case, one of the minimally invasive methods can be used to remove the tumor. Surgical operation here is often not required. The use of a laser or liquid nitrogen will be enough. Removal of the uterus is possible only if the cancer recurs after previous treatment. In case of initial tumor hysterectomy is not used.

When the doctors detect adenocarcinoma, the prognosis is worse. This is more aggressive kind of tumor. Therefore, more radical treatment is required. In this case, minimally invasive techniques are not used. The only options for treating preinvasive cervical cancer remain conization or hysterectomy. Moreover, removal of the uterus is considered to be the preferred method of treatment, since it is more productive. The сonization is applied only in case the woman wishes to retain reproductive function. But after she gives birth to a child, it is desirable to perform a hysterectomy.

At stage 0, in the case the patient visits a doctor on time, the prognosis is favorable. The five-year survival rate is 93%.

Cervical cancer stage 1

At stage 1 of cervical cancer, the oncological formation continues its growth. But it does not extend beyond the boundaries of the cervix. The tumor also does not reach the corpus. Cervical cancer of the 1st degree is divided into two sub-stages - A and B. Sub-stage A has a more favorable prognosis.

Sub-stage 1A is a microinvasive cervical cancer. The oncological formation is so small that it can be determined only with the help of microscope. The horizontal growth of the neoplasm does not exceed 7 mm. The cancer sprouts in depth no more than 5 mm. It does not matter whether the arteries, veins and lymphatic vessels are involved in the pathological process. This factor affects the choice of treatment methods, but is not reflected in the classification of cervical cancer.

Within this sub-stage itself, there are two more differentiations the first and the second sub-stages. They differ in the size of the primary tumor:

• 1 - stromal invasion (growth of neoplasm in depth) is up to 3 mm, and horizontal distribution is less than 5 mm
• 2 - the tumor grows in the depth more than 3 mm, but less than 5 mm, and  5-7 mm in width

Substage 1B is the first stage of cervical cancer in which cancer formation can be determined macroscopically (i.e. with the naked eye) or if the microscopically visualized tumor is larger than that characteristic of stage 1A. In this case, the prognosis of the disease is less favorable.

Within this sub-stage itself, there are two more differentiations the first and the second sub-stages:

• 1 -  the maximum measurement of the tumor is less than 4 cm
• 2 - the size of the neoplasm exceeds 4 cm

Treatment on the stage 1A1 involves conization of the cervix - if the woman wants to preserve reproductive function. In the future, the edges of the wound would be examined. If atypical cells are found in them, it is recommended to expand the scope of the operation. In this case, the whole cervix and the vaginal area adjacent to it is removed.

When the woman has cervical cancer of the first stage and she does not need to preserve fertility, a simple hysterectomy is performed. In the case of neoplasm in the lymph nodes and blood vessels, removal of pelvic lymph nodes is performed.

Similar treatment is used for stage 1A2. Only in this case it can be supplemented by radiotherapy, including remote and contact irradiation. And in case of detection of abnormal cells in the edges of the wound or lymph nodes at the first stage of cervical cancer chemotherapy is prescribed. Chemoembolization is also performed in eligible patients.

In the case of stage 1B, the treatment plan is the same as for 2A. Read about it in the section devoted to the treatment of cervical cancer at the 2nd stage. This is so due to the fact that the prognosis at 1B is much worse.

If at stage 1A the five-year survival rate  is 93% (it is the same as with non-invasive cervical cancer), then at 1B it is less, about 80%.

 

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Cervical cancer stage 2

Cervical cancer Stage 2 is characterized by the spread of the neoplasm beyond the cervix. In this case, the pathological process does not involve the distal (located closer to the vulva) third of the vagina and the pelvic wall.

There are two substages A and B. The choice of the substage depends on the fact, if the invasive cancer of the cervix has affected the parametrium. This term refers to the periarticular fiber - a layer of loose connective tissue surrounding the organ. If the neoplasm does not grow into a parametrium, 2A stage is diagnosed. If it grows out, then the stage of cervical cancer is defined as 2B stage.

Within 2A stage itself, there are 1 and 2 substages. Their difference is in the following factors:

• 1 – tumor is less than 4 cm
• 2 – the neoplasm exceeds 4 cm in the maximum diameter

At the 2A stage of cervical cancer, preservation of reproductive function is still possible. At 2A1, surgery for saving the organs is performed. This can be the removal of the cervix, upper vagina and pelvic lymph nodes.

Treatment options for women who do not need to maintain fertility in stages 1B and 2A1:

• Radical hysterectomy – removal of the uterus, pelvic and para-aortic lymph nodes
• Irradiation – is carried out if tumor cells are found in the lymph nodes or wound margins, as well as during the growth of the neoplasm into the lymphatic and blood vessels or stromal tissue (connective tissue structures supporting the bladder and uterus)
• Remote radiation therapy, brachytherapy and chemotherapy – in case of tumor spread in perimetrium (brachytherapy is prescribed after irradiation and taking medication)
• Brachytherapy – as the main method of treatment in case of contraindications to or refusal of surgery
• Uterine artery chemoembolization; chemoembolization combines advantages of the conventional uterine artery embolization with local effects of chemotherapeutic drugs

At stages 1B2 and 2A2 (when a tumor size is greater than 4 cm), organ-preserving surgeries are not performed. The treatment is always combined. A radical hysterectomy is performed, and then, if cancer cells are found in the lymph nodes and wound edges, chemotherapy and irradiation are performed. Chemotherapy, radiation therapy and chemoembolization can also be performed prior to surgery in order to improve the resectability of the tumor.

The life expectancy of patients depends on the fact, if the neoplasm grows into the perimeter. At the stage of cervical cancer 2A, the five-year survival rate is 63%. At 2B stage, it is under 58%.

Cancer of the cervix at the stage 3

If  woman has cancer of the stage 3, it means that the disease has led to hydronephrosis and to the kidney dysfunction, or the tumor tissue has infiltrated into such structures as:

• Perimetrium of the pelvic wall
• The lower third of the vagina

Cancer of the cervix at stage 3 is A and B. If the neoplasm spreads to the entire perimetrium, but does not reach the pelvic wall, 3A stage is indicated. But if the oncological formation has spread to the pelvic wall or caused kidney dysfunction, cervical cancer at stage 3 is defined as  stage B .

The stage 3 of cervical cancer is usually treated without surgery. A surgical intervention does not significantly affect the life expectancy. Surgical treatment is also not required at stage 2B.

Five-year survival of patients at stages 3A is 35%, and at 3B stage is 32%. It is possible to increase the life expectancy by using chemotherapy and radiation therapy.

Cervical cancer stage 4

This stage is classified if the neoplasm spreads beyond the pelvis, into the rectum or bladder. Cervical cancer of stage 4 is divided into A and B stages. Substage A is determined when the tumor infiltrates into the nearby organs (e.g. intestines, bladder). If distant metastases are detected (e.g. malignant loci in the lungs or bones), it means that the woman has cervical cancer at stage 4B. It is characterized by the most unfavorable prognosis and requires the most sophisticated therapeutic interventions.

Treatment usually does not involve surgery. The following stage 4 cervical cancer treatment options are used:

• Chemotherapy
• Radiation therapy in the form of remote irradiation
• Radiation therapy in the form of brachytherapy (the internal introduction of radioactive granules that affect the tumor tissue)

At stage 4B, brachytherapy is usually not used. Only such stage 4 cervical cancer treatment options as chemotherapy, targeted therapy and external radiation are desirable. The exact number of techniques used determines the cost of treatment for cervical cancer stage 4. This treatment plan slows down the growth of the tumor and reduces symptoms. Duration of treatment, e.g. number of chemotherapy courses, also influences the cost of treatment for cervical cancer stage 4. Five-year survival rate is 15%.

Distribution of metastases at different stages of the cervical cancer

Cervical cancer induces metastases which can be regional and remote. Regional metastasis occurs when the tumor cells spread to nearby lymph nodes.

They include:

• Paracervical region
• Parametrical region
• Internal, external and common iliac
• Obturatorial region
• Sacral lateral region
• Presacral region

It is important to know where the metastases of cervical cancer spread, in order to correctly determine the stage of the pathological process. After all, if metastases have occurred in other lymph nodes, in addition to those listed above, such metastases are considered remote. Metastases of cervical cancer in paraaortic nodes are also named remote. When there are distant metastases, regardless of the size and location of the primary tumor, cervical cancer stage 4 is diagnosed.

In this case, the detached tumors can be detected in the following areas:

• Distant lymph nodes
• Liver
• Central nervous system (brain)
• Bones

There are other organs, to where cervical cancer metastasizes. However, in most cases, detached tumors are observed in these anatomical structures. If distant metastases of cervical cancer are detected, surgical treatment is not advisable. Only radiation therapy in the form of remote irradiation and chemotherapy are desirable. Such treatment is considered palliative. It has little effect on life expectancy, impacting mainly its quality.

Peculiarities and costs of stage 4 cervical cancer treatment options

As it was mentioned before, stage 4 cervical cancer treatment options include mostly the systemic treatments and different modalities of radiation therapy. Local treatments, such as surgery or chemoembolization, may be used in separate women for alleviating symptoms and improving quality of life. However, doctors always inform patients about all possible stage 4 cervical cancer treatment options, including their availability in the healthcare facility, benefits and risks, cost of treatment for cancer stage 4, etc.

Radiation therapy for stage 4 cervical cancer includes external and internal irradiation. Most women receive both types of radiotherapy during their treatment course. First, the external beam radiotherapy is performed during 4-6 weeks. Fortunately,  a woman does not need to stay at hospital during this time, the procedure is performed on an outpatient basis. After that, internal irradiation is performed. Internal irradiation allows for more precise destruction of malignant cells and delivering higher doses of radiation to the target region without affecting surrounding healthy tissues. Implantation of the radiation source is performed in the operating room. A woman needs to stay at hospital for few days.

Chemotherapy is mostly used at stage 4B for controlling the symptoms. Combinations of chemotherapeutic drugs, such as cisplatin and gemcitabine or paclitaxel and topotecan, are used. In addition, chemotherapy enhances the effect of radiation therapy and vice versa.

Targeted therapy is usually administered along with chemotherapy. Targeted drugs for cervical cancer are angiogenesis inhibitors. This means that they suppress the formation of tumor blood vessels which leads to its deprivation of oxygen and nutrients. Such deficits finally lead to slowing down the tumor growth. The most widely applied targeted medication is bevacizumab, a monoclonal antibody that targets the vascular endothelial growth factor (VEGF).

Cost of treatment for cancer stage 4 may be no less significant for a patient than the availability of novel treatment options, especially for patients without a health insurance. Self-payers may take a look at the average cost of treatment for cancer stage 4:

1. Diagnostics of cervical cancer – 4,410 EUR
2. Cost of treatment for cervical cancer stage 4 with radiation therapy and chemotherapy – 32,400 EUR
3. Rehabilitation after the performed treatment – 1,580 EUR per day

Actually, the exact cost of treatment for cervical cancer stage 4 can be determined only after the treatment completion. Even the most qualified physician can not predict for sure if a woman will need additional examinations, therapeutic interventions, consultations of the related specialists, rehabilitation, etc. In addition, some hospitals may ask for additional deposit up to 30-40% of the estimated cost of treatment for cervical cancer stage 4. The deposit covers costs of unscheduled medical procedures.

 

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Treatment in Germany

Thousands of women with cervical cancer undergo treatment in Germany annually. Patients visit this country to get better medical services. The best option is to undergo treatment for uterine tumors in large academic and university hospitals, such as:

• University Hospital Rechts der Isar Munich, Department of Gynecology, Mammology, Obstetrics and Perinatal Medicine
• University Hospital Tuebingen, Department of Adult and Pediatric Gynecology, Mammology, Obstetrics
• Leverkusen Clinic, Department of Gynecology, Urogynecology, Mammology and Obstetrics
• University Hospital Ulm, Department of Obstetrics, Adult and Pediatric Gynecology
• University Hospital Carl Gustav Carus Dresden, Department of Adult and Pediatric Gynecology, Mammology, Obstetrics and Reproductive Medicine

You also can take advantage of the latest achievements of world medicine and undergo minimally invasive surgery, chemoembolization, targeted radiation therapy, chemotherapy with innovative medicines and other treatments in one of the German clinics. In order to do this, you can just fill in the application form on the Booking Health website.

We can also do the following:

• We help you choose the specialized hospital with modern equipment and qualified physician
• We elaborate the preliminary medical program, from diagnosis making to choosing between most efficient stage 4 cervical cancer treatment options
• We translate the medical documentation into German and vice versa, into your native language
• We will help you to apply for visa, both for the patient and an accompanying person
• We will book flights and accommodation for you and an accompanying person
• We will find an interpreter in Germany, who will help you communicate with healthcare professionals
• We will meet you at the airport and transport you to the clinic
• We will help to save up to 70% of the medical program cost, as we exclude additional fees and coefficients of foreigners from the final calculation, even if it concerns cost of treatment for cancer stage 4
• We will provide insurance that guarantees that the initial cost of the therapeutic program agreed on does not change, even if this is cost of treatment for cancer stage 4 (if it increases, all the extra costs will be covered by the insurance company)

For many years Booking Health company has been a leader in the medical tourism market. Thanks to the well-coordinated work of our specialists who fully organize your treatment in Germany, you will be able to concentrate on restoring your health. Visit the Booking Health website, fill in the "Sent request" form, and a patient case manager or medical advisor will contact you. A Booking Health specialist will guide you through all stages of undergoing treatment and rehabilitation in the most authoritative hospitals of the world.

 

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Authors:

The article was edited by medical experts, board certified doctors Dr. Vadim Zhiliuk, Dr. Nadezhda Ivanisova. For the treatment of the conditions referred to in the article, you must consult a doctor; the information in the article is not intended for self-medication!

 

Sources

American Cancer Society

National Cancer Institute

Medscape

 

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