- Ovarian Cancer Programme
Ovarian cancer is a relatively rare tumour (incidence: 12 new cases every 100,000 women/year, roughly 5,000 cases/year in Italy) which chiefly affects women between 55 and 75 years of age. It is a complex disease both from an aetiological and from a therapeutic point of view, the prevention, diagnosis and treatment of which require multiple specialist competencies which are only fully available in centres of excellence.
- The multidisciplinary approach
The Institute's Interdisciplinary Care Group (G.I.C) for gynaecological tumours guarantees a truly multidisciplinary approach to ovarian cancer, as provided for by the principal international guidelines as well as by the Oncology Network of Piedmont and Aosta Valley (http://www.reteoncologica.it/area-operatori/groups-per-pathologies/pathologies/tumours-ginecologici/gic-aziendali/335-torino-ovest/1048-gic-tumours-ginecologici-irccs).
This organization's primary goals are: to harness the various specialist competencies present within the Institute, to offer patients the best care and to conduct clinical translational research projects in order to test new therapeutic strategies.
Post-menopausal hormone replacement treatment and, limited to some rarer forms, endometriosis and hormone treatments for infertility are potentially modifiable risk factors for ovarian cancer. Among protective factors may feature young age at first pregnancy and multiparity, as well as prolonged use of oral contraceptive and breastfeeding. In contrast, the most important risk factors such as age and family history of tumours of the ovaries and of the breast (and to a lesser degree for other carcinomas such as those of the endometrium and of the colon) are not modifiable. For families with a particularly high concentration of such tumours, the Institute provides a genetic consultation and subsequent undertaking of genetic testing which may reveal the presence of a germline mutation of certain genes (BRCA1/2, MSH2, MLH1, PMS1 and PMS2) and consequent hereditary transmission of the risk of developing these neoplasms (hereditary breast and ovarian cancer syndrome, Lynch syndrome II).
For those women with no risk factors there are no tests programmed to identify ovarian cancer in the asymptomatic stage. Studies underway currrently, however, are assessing the impact of screening for women from families where there is a high risk due to hereditary factors, and, above all, for carriers of an established genetic mutation. For these women the Institute offers a dedicated service which also facilitates the scheduling of blood tests (dosage of CA 125 in the blood serum) and instrumental (pelvic and transvaginal ultrasound, mammary MRI and mammography), and provides specific psycho-oncological support both before and after any necessary performance of genetic tests. For carriers of an established genetic mutation, in order to prevent the disease, prophylactic surgery (removal of tubes and ovaries or oophorosalpingectomy, with or without removal of the uterus or hysterectomy) to be performed generally after the age of 40, once the patient's reproductive plans have been satisfied.
In most cases the symptoms of ovarian cancer are generally non- specific and are basically represented by swelling or abdominal-pelvic pain, difficulty in feeding or in digestion and urinary discomfort. The appearance of these symptoms, especially if frequent and progressively worsening, warrants specialist assessment of any further blood tests or imaging tests required.
For those women in whom a pelvic mass has already been detected, there is also a service for II level pelvic transvaginal ultrasound staffed by personnel certified to conduct the test in line with International Ovarian Tumor Analysis (IOTA) standards and a facilitated course of action for the scheduling of further investigations and possible intervention if tubo-ovarian disease is suspected.
Ovarian cancer treatment is a typical example of the added value offered by a multidisciplinary clinical approach. In the diagnostic stage gynaecologist and surgeon interact closely with radiologist, oncologist, nuclear medicine specialist and anatomical pathologist to establish the nature and extent (staging) of the disease.
Once this phase is concluded, a collegial meeting of the Gynaecological GIC establishes a diagnostic therapeutic plan of care (PDTA) (http://www.reteoncologica.it/images/stories/PDTA_Aziendali/PDTA_Ginecologici/Area_Torino_Ovest/ALL13-Del775-2.pdf) which is proposed to the patient and then promptly put into action.
Surgery, chemotherapy and the new targeted biological therapies are all very effective approaches to the treatment of ovarian cancer and are employed as appropriate according to the characteristics of the neoplasm, to its diffusion and to the patient's clinical situation.
- Treatment - Surgical therapies
In the event of early-stage lesions surgical treatment may make exclusive use of minimally-invasive techniques (laparoscopic surgery) and may also allow for the preservation of the patients' fertility (“fertility sparing”surgery). Laparoscopic surgery may also be valuable in advanced-stage lesions for the application of specific diagnostic algorithms (laparoscopic scoring) which are useful in directing the patient towards surgery in the first instance (primary cytoreduction) or to preoperative medical therapy followed by surgery (interval cytoreduction). Cytoreductive surgery is generally performed by means of laparotomy and is intended to remove all disease visible to surgical exploration. As the tumour may be located in various abdominal sites (apart from tubes and ovary, uterus, pelvic and abdominal peritoneum, small and large intestine, liver, omentum, diaphragmatic peritoneum, spleen, pelvic and paraaortic lymph nodes), its total removal may be complex, but it does guarantee a significantly improved prognosis. The main international guidelines emphasize that if this type of surgery is to be effective it requires the involvement of gynaecologists, surgeons and anaesthetists with specific experience in the treatment of ovarian cancer and that it must therefore be performed in centres of excellence (http://ebooks.esgo.org/ovarian-surgery-guidelines/mobile/index.html#p=1). One particularity of the Institute is the close and productive collaboration of the Departments of Oncological Gynaecology and Oncological Surgery in the complex surgical approach to patients with ovarian cancer and the consolidated experience of the surgeons in the treatment of peritoneal carcinomatoses originating from ovarian cancer and from other neoplasms (carcinomas of the gastrointestinal tract, mesotheliomas)
- Treatment -Medical therapies
Ovarian cancer is considered to be a generally chemosensitive tumour for which, except for a small number of low-grade initial tumours, chemotherapy is normally indicated. In our Medical Oncology Department, a group of dedicated oncologists studies the medical therapy of this neoplasm. Those patients who undergo primary surgery receive all the cycles of chemotherapy intravenously after the operation, while those who undergo primary chemotherapy receive part of the same before surgery and the rest of the chemotherapy after the operation. The traditional chemotherapeutic agents have recently been supplemented with new molecular targeted therapies such as bevacizumab, an anti-angiogenic agent which is administered in some subgroups of patients with advanced disease during chemotherapy and as maintenance after its conclusion. In the event of recurrences of disease the therapeutic options, in addition to any further surgical intervention, include the use of the same as a first line of action and of new drugs according to the duration of the interval in which the patient has been free from disease and to the patient's general state of health. For those patients with platinum-sensitive recurrence and somatic or deleterious germline mutation of genes BRCA1/2, a new important therapeutic option is represented by the PARP inhibitors, a class of drugs which selectively interferes with the capacity to correct DNA defects in the mutated cells (olaparib, niraparib).
- Treatment -Experimental therapies
The Department of Medical Oncology participates in and coordinates numerous phase II and III national and international multi-centre clinical studies with chemotherapeutic agents and molecular targeted therapies in various stages of disease (Active protocols).
The Department of Oncological Surgery is home to one of the major Italian groups operating in the field of the integrated treatment of cytoreductive surgery and hyperthermic intraoperative chemotherapy (Hyperthermic Intraperitoneal Chemotherapy or HIPEC). The efficacy of post-operative intraperitoneal chemotherapy administered by catheter in ovarian cancer is substantiated by numerous randomized studies (http://ascopubs.org/doi/abs/10.1200/JCO.2014.55.9898?url_ver=Z39.882003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&), but its diffusion worldwide has to date been limited by the complications associated with the treatment. HIPEC, in contrast, in addition to potentially offering a further therapeutic effect constituted by the warming of the chemotherapeutic agent administered intraoperatively, is not associated with the complications typical of chemotherapy administered postoperatively via abdominal catheters. In a recent randomized study on patients with advanced ovarian cancer HIPEC administered at the conclusion of interval cytoreduction surgery seems to produce a significant improvement in prognosis, without significantly increasing the complications associated with surgery alone. (http://www.nejm.org/doi/full/10.1056/NEJMoa1708618). Moreover, experimental protocols in pressurized intraperitoneal aerosol chemotherapy (PIPAC) are also active for patients in an advanced stage of the disease.
- Treatment - Support therapies
Specialists in psycho-oncology, nutrition, and palliative care are an integral part of the gynaecological GIC and work alongside the other specialists throughout the whole process of diagnosis and therapy for patients with ovarian cancer.
- Translational research
Ovarian cancer is a disease characterized by extreme genetic heterogeneity even at an intratumoral level. The Institute has an active research programme in which the patients' tumours and ascites are transplanted and propagated in immunocompromised host organisms (patient derived xenografts or PDX and organoidi) in order to study the phenomenon of tumoral heterogeneity, resistance to treatments and to identify personalized therapies on the characteristics of the individual patient's tumour (http://www.ircc.it/irccit/?q=Cancer-Genetics).
Gynaecological Oncology: Riccardo Ponzone (Doctor), Alessandra Magistris (Doctor), Francesco Marocco (Doctor), Furio Maggiorotto (Doctor)
Oncological Surgery: Michele De Simone (Doctor), Marco Vaira (Doctor), Armando Cinquegrana (Doctor)
Medical Oncology: Giorgio Valabrega (Doctor).