Gynecological tumors: silent enemies

There are diseases that make no noise, yet they change the lives of thousands of women every year. Gynecological tumors often develop silently, with vague or easily mistaken early symptoms. «When we talk about gynecological tumors, we mean five different cancers, since every gynecological organ can potentially get sick, but the most common are cervical, uterine, and ovarian cancer», explains Professor Domenica Lorusso, head of the gynecological oncology program at Humanitas in Milan.

Not all uterine cancers are the same: in recent years, research on tumor DNA has made it possible to identify differences among the various subtypes, each with specific molecular features that influence treatment response. These discoveries are paving the way for increasingly targeted and personalized therapies.

«For example, tumors with mutations in a group of genes known as mismatch repair genes respond very well to immunotherapy, either alone or combined with chemotherapy. On the other hand, tumors with mutations in another gene, the mutated P53, are likely those that respond best to a different class of drugs, the PARP inhibitors, which we combine with chemo and immunotherapy specifically for these patients», says Lorusso.

Prevention and immunotherapy are changing outlooks

Cervical cancer is among the most aggressive, affecting younger women compared to uterine cancer.

«It’s a cancer we know a lot about. For instance, we know that in 90% of cases, it is linked to papillomavirus infection,” notes the professor. “Knowing the enemy is always a way to fight it better, and therefore to prevent it. Today, for this disease, we have primary prevention with HPV vaccines and secondary prevention with Pap tests and HPV tests».

This knowledge is also valuable in terms of therapy. The introduction of immunotherapy combined with radiotherapy, especially in locally advanced, high-risk stages, has dramatically changed treatment prospects. «This allows us to increase survival by around 50%, a result we haven’t seen in cervical cancer for over 25 years», Lorusso states.

Gynecological tumors: between personalised treatments and new hope

In the past two years, treatments for uterine cancer have undergone a real revolution thanks to immunotherapy. Initially, it was used alone in patients with microsatellite instability who had failed previous chemotherapy cycles. Today, this therapy is also combined with chemotherapy for patients with advanced or recurrent disease. «The results are extraordinary – explains Lorusso – in terms of delaying recurrence and, in some cases, increasing survival itself, making us almost imagine that, even in patients with very advanced and relapsed disease, these combinations can actually cure a significant number of them».

At the same time, a second class of drugs, PARP inhibitors, has been applied to endometrial cancers. «They interact with the genetic repair mechanisms. We’ve known them well, using them for a long time in ovarian cancer. We’ve discovered they also work in uterine cancer. For now, we cannot yet identify precisely which patients benefit the most. But, having identified factors that predict PARP inhibitor response in ovarian cancer, we are to some extent transferring this knowledge to endometrial cancer».

Another frontier is represented by antibody–drug conjugates, an innovative method of administering chemotherapy. «The chemotherapy drug is linked to an antibody that recognizes a receptor on the tumor cell. They bind, and the chemotherapeutic agent is carried inside the tumor cell, internalized, and released where it is needed. We expect the results of the first study comparing an antibody–drug conjugate with standard chemotherapy around the middle of next year. This could be the first drug approved for uterine cancers», Lorusso declares.

Ovarian cancer: the silent killer

Ovarian cancer is often called the “silent killer” among gynecological tumors. Not because it gives no symptoms, but because they are subtle and easily confused with common conditions such as colitis or diverticulitis.

«Today, ovarian cancer is at the very center of research and must be managed in specialized centers, where surgeons are experienced enough to determine the patient’s pathway from the time of diagnosis. This may involve surgery immediately or after chemotherapy. Reference centers also have molecular pathologists who help us identify which of the 345 ovarian tumor types we are treating—because today, more than ever, ovarian cancer requires personalized care».

A Network of Experts at the Service of Patients

The treatment of gynecological cancers requires a multidisciplinary approach: the involvement of a single specialist is not enough. «The surgeon plays an essential role, but we also need a medical therapy expert, whether a gynecologist or oncologist, who specializes in that disease. And we must not forget other figures who are not secondary but necessary: the dedicated pathologist who tells us which tumor we are treating, the molecular pathologist who clarifies which type of tumor we are dealing with, as well as the psycho-oncologist, research nurse, and specialized radiologist».Specialised centers also offer access to clinical trials, which bring new treatment opportunities along with experimental drugs. Today, research is advancing at an unprecedented pace. As Lorusso notes: «The literature is very clear on this. Patients treated in research centers, in reference centers, live longer. Today, this is a fact».