Uterine cancer develops when cells in the uterus begin to grow out of control. The most common form is endometrial cancer, which starts in the inner lining of the uterus and accounts for about 90% of all cases. Understanding where this cancer spreads first is important because the extent of its spread, or metastasis, significantly affects treatment planning and prognosis. Cancer cells break away from the primary tumor and travel through predictable pathways that determine the stage of the disease.
Mechanisms of Uterine Cancer Spread
Cancer cells use specific routes to leave the uterus and establish new tumors elsewhere in the body.
The most straightforward path is direct extension, where the tumor grows outward and invades adjacent structures. The depth of this invasion into the muscular wall of the uterus, called the myometrium, is an important factor in staging the cancer.
Another major route is lymphatic spread, which is the most common way uterine cancer travels beyond the immediate area. Cancer cells enter the lymphatic vessels, carrying them to regional lymph nodes for filtration, where they can multiply and move on.
The third mechanism is hematogenous spread, where cancer cells enter the bloodstream directly. This route is responsible for metastasis to distant organs far from the pelvis. A less common mechanism for aggressive subtypes is peritoneal or transtubal spread, where cells shed from the tumor travel through the fallopian tubes and implant on the surfaces of the abdominal cavity.
Initial Regional Sites of Metastasis
The first destination for uterine cancer cells is typically determined by the primary tumor’s location and the nearest lymphatic drainage points. The pelvic lymph nodes are the primary regional site where cancer cells arrive. These nodes include the internal iliac, external iliac, and obturator groups, which filter the pelvic region.
Involvement of these pelvic lymph nodes is a major step in the advancement of the disease, often classifying it as Stage III cancer. Beyond the immediate pelvic region, the cancer may spread next to the para-aortic lymph nodes, which run alongside the aorta. Their involvement signifies a wider regional spread and is a key component in determining the cancer’s stage.
Cancer can also spread locally through direct extension into adjacent reproductive structures. The cancer commonly invades the cervix, the lower part of the uterus, often classifying the tumor as Stage II disease. Direct spread can also involve the fallopian tubes and the ovaries, which can be reached through lymphatic vessels or by direct surface spread.
Progression to Distant Organ Spread
Once the cancer has bypassed the regional lymph nodes and entered the bloodstream, it forms distant metastases, characteristic of advanced Stage IV disease. The most common distant site for uterine cancer to spread is the lungs, occurring in nearly 30% of distant cases.
The liver is the second most common site, accounting for approximately 15% of distant metastases. Spread to the liver often suggests a more challenging prognosis compared to other sites. Other distant locations include the bones, reported in about 10% of cases, and the brain, which is rare, occurring in only about 3% of cases.
Distant metastasis requires systemic treatments to address tumors throughout the body. While the lungs and liver are the primary targets, the cancer may also spread to distant lymph nodes outside of the pelvis and abdomen, such as those near the collarbone. The pattern of spread depends heavily on the specific subtype of uterine cancer, with aggressive types showing a greater propensity for early distant travel.
Clinical Assessment of Tumor Spread
Medical professionals determine the extent of uterine cancer spread using imaging and surgical evaluation. Imaging techniques like Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET) scans visualize the tumor and check for spread to lymph nodes or distant organs. MRI is often the preferred modality for assessing the depth of myometrial invasion within the uterus.
The definitive assessment is achieved through surgical staging, which involves surgically removing the uterus, ovaries, and fallopian tubes, and often sampling the lymph nodes. Tissue samples are pathologically examined to determine the full extent of the disease. This procedure confirms whether the tumor has invaded the uterine wall or spread to the pelvic and para-aortic lymph nodes.
The International Federation of Gynecology and Obstetrics (FIGO) staging system is the standardized method for classifying the spread of uterine cancer. This system uses stages I through IV, with Stage I confined to the uterus and Stage IV indicating distant metastasis. The FIGO staging, updated in 2023, incorporates factors like histological type, grade, and molecular characteristics to provide a more accurate prognosis and guide treatment decisions.