Pathology
Colorectal cancer is one of the most common malignancies and affects the large intestine, which has the main function of absorbing water and compacting feces and is divided into colon (ascending, transverse, descending, and sigma) and rectum (the end part near the anus). Over the past two decades, the incidence of this malignancy has increased, but in parallel, survival rates have improved due to earlier diagnosis and more effective treatments.
Types
Most colorectal cancers result from the malignant transformation of polyps, small growths of the intestinal mucosa that are considered precancerous forms. Not all polyps have the same risk of evolving into cancer, but it is critical to monitor and remove them when necessary to prevent cancer from occurring.
Histologically, the most common tumor is adenocarcinoma, which develops from the epithelial cells of the intestinal mucosa. There are various subtypes, including the mucinous or castellated ring cell subtype, which may have special features.
Colorectal cancer presents differently depending on the site: the sigma and rectum are the most frequently involved areas (more than 50% of cases), followed by the ascending colon, with about 20% of cases. While colon cancer affects men and women similarly, rectal cancer is more common in men, with a ratio of about 2 to 1.
The numbers in Italy
According to the AIRTUM Registry (Italian Association of Cancer Registries), in 2023 in Italy colon-rectal cancer recorded about 50,500 new diagnoses (men = 26,800; women = 23,700). This cancer has a strongly age-related incidence, with 90% of cases diagnosed in people over 50 years old.
Risk factors
In most cases, the precise cause of colorectal cancer remains unknown. However, there are several factors that may increase the likelihood of developing this neoplasm:
- Diet: a diet high in fat and animal protein, particularly high consumption of red meat and low in fiber (fruits and vegetables) can contribute to increased risk, which may be even higher if alcohol is also widely used.
- Obesity, smoking and sedentary lifestyle: may increase the risk of developing colorectal cancer.
- Bowel disease: those with chronic inflammatory bowel disease, such as ulcerative colitis or Crohn’s disease, have a higher risk of developing this type of cancer.
- Hereditary genetic alterations: having close relatives (parents, brothers, or sisters) in the family with colorectal cancer diagnosed at a young age (e.g., under age 45) or in multiple members of the same family may indicate a hereditary predisposition. In such cases, the physician may refer the patient to specialized centers for genetic testing, which is useful in assessing risk and, if necessary, scheduling more frequent and targeted checkups.
Only about 5% of colorectal cancers are due to inherited genetic mutations. The two main genetic syndromes linked to increased risk are:
- Familial adenomatous polyposis (FAP): characterized by the formation of numerous benign polyps in the colon that, unchecked, can develop into malignant tumors;
- Hereditary nonpolyposis-associated colo-rectal carcinoma (HNPCC): in this condition, intestinal tumors can appear at a young age and affect different areas of the intestine.
Symptoms
Signs of colorectal cancer may include:
- Light or dark red blood in the stool
- Changes in alvus, such as diarrhea or constipation, persisting for more than six weeks
- Unwarranted weight loss
- Abdominal or anal pain
- Feeling of incomplete evacuation
Often fatigue can be experienced, especially if the tumor causes bleeding and anemia, which can also cause breathing difficulties. In some cases, intestinal obstruction causes nausea, vomiting, abdominal pain, and a sense of fullness.
Although these symptoms may depend on other conditions, it is critical to always consult a physician for evaluation.
Diagnosis and examination
The diagnostic pathway usually begins to ascertain the cause of suspicious symptoms detected by the family physician, or after occult blood in the stool has been detected as part of regional screening programs for early detection of colorectal cancer. If colorectal cancer is suspected, a number of instrumental tests can be performed of which the first and most important is colonoscopy.
A computed axial tomography (CT) scan of the chest and full abdomen with contrast medium and, in the case of rectal neoplasms, a nuclear magnetic resonance imaging (MRI) of the pelvis may be required to complete staging, i.e., assessment of the extent of disease.
Colonoscopy
Colonoscopy is an endoscopic examination that is performed at the Division of Gastroenterology and Digestive Endoscopy; it allows the gastroenterologist to examine the inner wall of the intestine, starting from the rectum and going up to the colon, using the colonoscope, a probe mounted on a long, flexible tube and equipped with a video camera, which is inserted into the rectum and sends images back to a computer screen. The probe also allows the physician to take abnormal tissue fragments (thus to take biopsies) or to remove any polyps (or adenomas) -excrescences that form on the inner wall of the intestine and can develop into tumors- which will then undergo histological examination.
The procedure, which is usually done on an outpatient basis, can be uncomfortable or even painful, so a mild sedative is usually administered. There is preparation in the days leading up to the examination, which is explained to the patient when booking the examination.
Virtual Colonoscopy
Virtual colonoscopy may be useful to complete the diagnosis when colonoscopy was not sufficient. It is performed at the Division of Radiodiagnostics and consists of a Low-dose radiation CT which allows the radiologist to obtain three-dimensional images of the intestines.
The procedure involves the oral administration of a contrast agent containing iodine and the introduction of a small rectal probe that causes no pain. However, this examination does not allow the removal of any polyps.
Once the presence of the tumor is established, other instrumental examinations may be necessary to assess the size, location, and possible spread of the disease to other organs.
The following exams may be performed to complete the diagnosis of colon cancer:
- CT scan of the abdomen and pelvis with contrast medium,
- Ultrasound of the abdomen,
- Chest X-ray.
For the diagnosis of rectal cancer, on the other hand, the following exams may be necessary:
- MRI of the pelvis with contrast medium,
- Transrectal ultrasonography,
- Echo-endoscopy.
Analysis of Tumor Markers in Blood
Through a blood test it is also possible to measure the amount of two particular proteins that may be produced by colorectal cancer cells (which is why they are called tumor markers): CEA (Carcino-Embryonic Antigen) and CA19-9. Their concentration is related to the extent of the tumor and usually increases as the tumor progresses, so these markers, when present, help assess the severity of the disease, follow the progress of the disease, and evaluate the effectiveness of treatment.
Histological and Cytological Analysis
Definitive diagnosis of colorectal cancer is obtained through histological examination, performed by a pathologist on tissue samples taken during colonoscopy.
The removed polyps are analyzed for shape, size, and cellular characteristics so as to determine their benign or malignant nature. If the polyp is malignant (adenocarcinoma), the cells are evaluated according to their degree of similarity to healthy cells, speed of growth, and ability to invade surrounding tissues. These elements make it possible to define the tumor’s degree of malignancy, generally expressed on a scale of 1 to 3.
Histological examination also applies to tissue fragments taken during colonoscopy in suspicious areas. If the tumor has already infiltrated the intestinal wall or other structures, it may be a sign of more advanced disease and a possible risk of metastasis.
This step is critical because it provides accurate information that guides the choice of the most appropriate treatment, allowing the care pathway to be tailored and increasing the likelihood of success.
Molecular Analysis
In the case of advanced or metastatic cancer, a molecular profile analysis of the tumor is done to identify possible alterations in disease genes. The information obtained from this analysis is important for establishing prognosis and planning the therapeutic strategy for each patient: indeed, certain alterations are associated with better or worse disease course and sensitivity to molecularly targeted drugs.
In particular, possible mutations in genes such as RAS and BRAF, which determine cell survival and proliferation, and mutations in MMR genes, which are involved in DNA repair functions.
Therapies
After the diagnosis is confirmed, specialists in the multidisciplinary team evaluate a number of factors to plan an individualized course of treatment for the patient. In addition to the type of tumor, its size, and whether it has spread to other parts of the body, the patient’s age, general health status, and medical history are also considered. The treatment plan is then discussed with the patient, proposing alternative choices in case of equivalent effectiveness.
Depending on the stage of the tumor, different treatment strategies are indicated, including surgery, chemotherapy, radiation therapy, interventional radiology, and molecularly targeted therapies:
- If the tumor is limited to the most superficial layer (stage I), surgical removal is sufficient.
- If the tumor affects deeper layers of the intestinal wall without affecting the lymph nodes (stage II), chemotherapy is recommended in cases with one or more unfavorable factors in order to reduce the risk of recurrence.
- Chemotherapy, on the other hand, is always indicated when the tumor has affected one or more lymph node (stage III); if it is rectal cancer, chemotherapy is given before surgery, in combination with radiation therapy, to reduce the size of the tumor mass;
- If the tumor has spread to other organs (stage IV), all different therapies including molecular targeted therapies and immunotherapy can be used when possible.
- For selected patients whose tumor has peculiar characteristics or for whom standard therapies had not proved effective, there is also the possibility of receiving experimental therapies within clinical trials conducted by the Institute’s researchers. In case this option is considered feasible by the multidisciplinary team, it will be proposed and explained to the patient with whom a shared decision will be made.
Endoscopic Treatments
Endoscopic treatment is often considered for early colorectal cancers, particularly carcinoma in situ or superficial tumors. These treatment options include:
- Endoscopic Mucosal Resection (EMR): it is an endoscopic procedure to remove superficial or precancerous lesions of the rectum without the need for open surgery;
- Endoscopicextended Submucosal Dissection (ESD): it is an advanced endoscopic technique to remove larger, invasive tumors that extend to the submucosa of the rectum.
Surgery
Surgery is performed in almost all cases of colorectal cancer, especially if the disease is in the early stages. Depending on the location and extent of the tumor, surgery may be more or less conservative.
If the tumor is small and in a very early stage, it is possible to remove it directly during colonoscopy, then endoscopically.
Even early and small rectal tumors, if their location permits, can be excised endoscopically through the anus.
If, on the other hand, the tumor has invaded part of the surrounding tissues, surgery is required, which, at the Candiolo Institute, is always performed, when possible, with minimally invasive, laparoscopic and robotic techniques, that is, using camera-equipped instruments that are introduced into the intestinal cavity through small incisions in the abdominal area. These procedures reduce hospital stay time and postoperative complications compared with traditional surgery.
The innovative minimally invasive surgery technologies available to the Institute – such as the 4K laparoscopic columns and the intraoperative fluorescence – offer the surgeon extremely detailed spatial orientation and enable them to perform maneuvers with the utmost precision in even complex surgeries.
During a colectomy, the surgeon removes the portion of the colon affected by the tumor along with nearby lymph nodes, and then reconnects the remaining ends of the bowel. When the surgeon needs to remove the final part of the intestine, or when it is necessary to keep the operated section of intestine at rest to promote healing, the colon is diverted and put in communication with the outside through an opening (stoma) created by the surgeon on the abdomen and connected to a stool collection bag. This procedure, called colostomy, in most cases it is temporary and thus normal intestinal transit is restored at a later surgery, but in some cases it can also be permanent.
In any case, physical and psychological rehabilitation of the patient is necessary after this type of surgery.
Recovery after Surgery – the ERAS Protocol
At the Candiolo Institute, surgery is complemented by a protocol of post-operative clinical and care management called ERAS (Enhanced Recovery After Surgery), which promotes rapid recovery of the patient autonomy after surgery, decreases hospitalization time and reduces the incidence of complications.
The protocol involves a team of different specialists (surgeon, anesthesiologist, dietitian, nurse, psychologist, physical therapist, social worker) who manage the patient’s journey in a coordinated manner, and is based on pain control, use of minimally invasive surgical techniques, preoperative counseling, and early postoperative rehabilitation.
It provides the patient with nutritional support that avoids pre-operative fasting, targeted anesthesia that allows rapid resumption of oral feeding, reduced use of tubes, drains, and IVs, and permits early mobilization.
Chemotherapy
Chemotherapy refers to the use of drugs designed to destroy or inhibit the growth of cancer cells by exploiting their higher rate of division compared with normal cells. Because these agents target cellular replication mechanisms, they can also affect healthy tissues, leading to side effects; however, these are usually temporary and tend to resolve after treatment ends.
Before starting therapy, the oncologist explains the prescribed drug and provides guidance on the behavior and measures to help minimize potential side effects.
In colorectal cancer, chemotherapy can be given at different points in the course of treatment:
- After surgery (adjuvant chemotherapy) to reduce the risk of disease relapse (recurrence);
- Before surgery (neoadjuvant chemotherapy) to reduce the tumor mass and facilitate surgical removal; in rectal cancers, neoadjuvant chemotherapy is combined with radiation therapy;
- When the tumor has spread to other organs, metastatic disease, chemotherapy may be used to relieve symptoms, improve quality of life, and extend survival. In selected cases, by shrinking the metastases, chemotherapy can also make it possible to incorporate additional treatment strategies for metastatic disease, such as surgery, interventional radiology, or radiotherapy.
There are many chemotherapy drugs and they are often used in combination with each other.
The way chemotherapy is administered varies depending on the type of tumor and the drugs: it can be taken orally, in tablet form, but more often it is administered intravenously. The intravenous administration is performed on an outpatient basis and its duration can vary from minutes to hours depending on the drugs used.
The chemotherapy is given “in cycles”: each cycle lasts for a few days and is followed by a few weeks of rest. The number of cycles depends on the type of tumor and, of course, the response to the drugs, which can vary greatly from patient to patient.
Biological Therapies (Molecularly Targeted Therapies)
Biological therapies, also called molecular targeted therapies or target therapies, are targeted treatments that selectively act on specific targets found primarily in cancer cells. These targets-such as receptors, enzymes, or growth factors-are involved in the processes that promote uncontrolled cell growth, resistance to traditional therapies, and the formation of new blood vessels that feed the tumor.
An important target in colorectal cancer treatments is the EGFR (epidermal growth factor receptor) protein. When this receptor is blocked, activation of the RAS gene, which is implicated in tumor proliferation and spread, can be disrupted. This is where specific drugs, such as cetuximab and panitumumab, laboratory-produced monoclonal antibodies that mimic the action of the immune system, act.
Another strategy is to inhibit angiogenesis, which is the formation of new blood vessels that allow the tumor to grow and spread. In this case, drugs such as bevacizumab and aflibercept block vascular growth factor VEGF.
These therapies are administered intravenously and, in most cases, are combined with chemotherapy in patients with advanced or metastatic disease. The goal is to improve treatment efficacy, slow disease progression and, when possible, prolong survival while maintaining a good quality of life.
Immunotherapy
Immunotherapy is a therapeutic approach that does not act directly on cancer cells, but reactivates the immune system’s defenses, which are often weakened or blocked by the tumor itself.
In colorectal cancer, research is investigating drugs that can “take the brakes off” the immune system, allowing it to recognize and eliminate cancer cells again. These drugs, called immune checkpoint inhibitors, have proven effective only in a subpopulation of patients (about 15 percent) whose tumor has a defect in DNA repair mechanisms (mismatch repair deficiency, dMMR).
At present, immunotherapy in the colorectum is used in experimental settings and mainly in some cases of metastatic disease, but preliminary results indicate promising potential, paving the way for increasingly personalized therapies.
Radiotherapy
Radiation therapy consists of the use of high-energy radiation targeted at the level of the tumor mass. It does not require hospitalization and is administered in consecutive daily sessions, from Monday through Friday.
Radiation therapy is not usually used for colon cancer, except when the disease is advanced (stage IV) or palliative purposes if it has developed metastases.
It is, however, indicated for the treatment of rectal cancers, usually in combination with chemotherapy. It can be administered before surgery (neoadjuvant therapy) to reduce tumor size or after surgery (adjuvant therapy) to lower the risk of local recurrence. It is also used palliatively in locally advanced rectal cancers to relieve symptoms and slow tumor progression.
Ongoing support
At the Candiolo Institute, the doctors and nurses of the multidisciplinary team are available to provide the patient with comprehensive support in managing the various side effects that may arise in the course of treatment.
Management of Side Effects
Treatment for colorectal cancer often involves side effects that impact quality of life more or less severely. However, they can be mitigated and in some cases prevented by specific treatments and/or appropriate lifestyle.
At the Candiolo Cancer Institute, doctors and nurses of the multidisciplinary team are available to provide the patient with comprehensive support to help manage the various side effects that may arise during the course of treatment.
Psychological Support
The impact of cancer extends beyond physical health and affects a person’s psychological well-being. A cancer diagnosis is inherently traumatic, influencing all aspects of life and often causing anxiety, fear, anger, and depression.
At the Candiolo Cancer Institute, alongside cutting-edge therapies, the treatment and care pathway always includes qualified psycho-oncological support that helps patients cope positively, not only with treatment, but also with the delicate phase of physical and psychological recovery.
Psychological support groups are available to connect with others who have experienced, or are experiencing, similar challenges.
Direct Line to Specialists
Cancer patients are often vulnerable and require support throughout their care journey. When they experience a symptom, whether related to the disease or a side effect of treatment, they should have prompt access to a specialist’s evaluation through a ‘fast-track’ system.
For this reason, at the Candiolo Cancer Institute there is an assistance service every day, from Monday through Friday, from 8 a.m. to 5 p.m.: just call the secretary of the Oncology Day Hospital (+39 011 993 3775) reporting the need for an urgent consultation, and the patient will be promptly contacted by their specialist.
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Continuing Care and Palliative Care
The care pathway for a cancer patient is not just about the disease, but about the whole person. Coping with cancer means living with physical symptoms, such as pain or weight loss, and with an emotional impact that can be profound. Therefore, comprehensive support that takes into account both the body and the mind is essential.
At the Candiolo Cancer Institute, who wishes or requires it can rely on a multidisciplinary team prepared to address every aspect of their health and well-being, offering:
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Nutritional support, to maintain strength and energy during treatments
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Psychological support, to deal with emotional difficulties and regain balance
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Physiotherapy, to preserve and recover mobility and quality of life
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Medication and management of venous access devices, to ensure safety and comfort
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Pain therapy, to minimize physical suffering
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Management of any other conditions, for comprehensive and personalized care
Genetic Counseling
Only 5% of colorectal cancer cases are caused by rare inherited genetic disorders.
The best known are:
- Familial Adenomatous Polyposis (FAP), due to mutations in the MUTYH gene, which increases the risk of developing other types of cancer in addition to colon cancer;
- Lynch syndrome, which increases the risk of developing colorectal cancer, as well as other cancers, before age 50.
The Candiolo Cancer Institute has an outpatient genetic counseling clinic where a geneticist, an expert in hereditary-familial cancers, offers cancer risk assessment counseling and genetic testing to patients who require it.
People at high genetic risk of developing colorectal cancer are placed in a specific diagnostic surveillance program.
Social Work
The Social Service Department of the Candiolo Cancer Institute conducts information and orientation interviews for patients and their families on how to access services in the area and how to obtain welfare and social security benefits provided by law (disability, benefits for aids and prostheses, work leave, etc.).
The service operates on Wednesdays and Fridays from 9 a.m. to 1 p.m. – Phone: +39 011 993 3059
Follow Up
With the conclusion of the treatment course begins an equally important phase: the follow-up phase.
During this period, scheduled visits and examinations are used to monitor therapy side effects, assess treatment effectiveness, and track the patient’s functional recovery.
Follow-up plays a key role: it allows early detection of any recurrence and early intervention with the most appropriate therapies.
For the patient, each follow-up appointment is also an opportunity to discuss concerns, report symptoms or new needs, and receive reassurance and personalized guidance from their physician.
The specialist sets up a tailored follow-up schedule, establishing frequency and type of examinations based on the early stage of the disease and the treatments received.
Generally, for colorectal cancer, the follow-up program includes:
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Medical examination and blood tests
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Every 3 months in the first 3 years
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Every 6 months in the 4th and 5th year
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Subsequently, once a year
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CT scan of chest and abdomen alternating with abdominal ultrasonography
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Every 6 months in the first 3 years
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Then annually until the 5th year
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Colonoscopy
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Within 1 year after surgery
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Then at 3 years old
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Every 5 years thereafter
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Follow-up typically extends for 5 to 10 years, with a closer follow-up frequency at the beginning, gradually thinning out over time, accompanying the patient on a surveillance course.
Multi Disciplinary Team
Every cancer requires a multidisciplinary approach at all stages of disease management. At the Candiolo Cancer Institute, this is provided by a team of specialists from various clinical and surgical departments, known as the GIC (Interdisciplinary Care Group or MDT). The GIC ensures that each patient is supported throughout the diagnostic and therapeutic process, including arranging and coordinating examinations and maintaining communication with the patient and their family.
For each patient, the GIC (MDT) defines and shares a personalized care pathway based not only on the type and stage of the tumor but also on the patient’s individual characteristics. The goal is to achieve the best possible outcomes both oncologically and functionally, while maintaining a high quality of life.
The Group also collaborates closely with the Institute’s researchers to provide patients with rapid access to the latest innovations in screening, diagnosis, and treatment.
Clinical Divisions
The diagnostic-therapeutic pathway for colorectal cancer at Candiolo involves several clinical divisions, including:
- Gastroenterology and digestive endoscopy
- Oncologic surgery
- Anesthesia and resuscitation
- Medical oncology
- Radiodiagnostics
- Nuclear medicine
- Radiotherapy
- Pathology
Clinical Studies
Researchers at the Candiolo Cancer Institute are actively engaged in numerous research projects, both national and international, dedicated to colorectal cancer. These studies aim to improve the efficacy of treatments, reduce their toxicity, and offer new therapeutic opportunities.
Major projects include:
- Use of liquid biopsy to personalize biological therapies: liquid biopsy is a test that, from a simple blood draw, allows the genetic-molecular profile of the tumor to be analyzed. This makes it possible to monitor the evolution of the metastatic tumor and adapt the treatment protocol in real time to overcome any drug resistance.
- New molecular-targeted therapies designed to combat forms of metastatic colon cancer that have developed resistance to standard treatments.
- Study of the role of diet, gut microbiome, and vitamin intake as modulators of the antitumor response and their impact on the immune system and treatment tolerance.
- Fluorescence-guided robotic surgery: this innovative technique is designed to facilitate the precise identification and removal of lymph nodes during colorectal surgeries.
In selected cases, patients treated at the Institute may have the opportunity to participate in these clinical trials, thus gaining access to innovative treatments that are not yet available in standard clinical practice.
Why Choose Us
At Candiolo Cancer Institute, every patient with colorectal cancer is treated in a highly specialized manner, thanks to the synergistic work of a dedicated Interdisciplinary Care Group (GIC).
Clinical Experience and Tailored Approach
Thanks to the large number of cases treated each year, the Candiolo Cancer Institute is a national reference center for the care of colorectal cancer. This extensive experience allows us to manage even the most complex cases, always using a personalized approach, tailored to the clinical and individual profile of each patient.
Imaging Technologies and Advanced Diagnostics
Establishing a treatment plan always begins with an accurate and timely diagnosis. Patients have access to state-of-the-art imaging technologies that enable precise assessment of disease extent.
Additionally, the Institute provides advanced laboratory investigations, including molecular and genomic analyses, which are essential for identifying the biological characteristics of the cancer and guiding therapeutic decisions.
Minimally Invasive Surgical Techniques and Multidisciplinarity
When appropriate, surgery is performed using minimally invasive techniques (laparoscopic or thoracoscopic), which minimize operative trauma, promote faster recovery, and enhance postoperative quality of life. All treatment decisions are made within the GIC (MDT), ensuring a coordinated and integrated approach.
Clinical Research and Access to Trials
As an IRCCS (Scientific Institute for Research, Hospitalization, and Healthcare), the Candiolo Cancer Institute combines clinical care with a strong focues on scientific research. Patients can be considered for participation in active clinical trials, offering access to innovative therapies not yet available in standard practice. This integration of care and research is a distinctive strength that translates into tangible benefits for patients.
Care and Support Every Step of the Way
The Interdisciplinary Care Group (GIC or MDT) supports the patient at every stage, from diagnosis to treatment and follow-up, addressing nutritional needs, psychological well-being, and reintegration into daily life. The scheduling of checkups, visits, and treatments is organized to ensure continuity and peace of mind, always prioritizing the human dimension of care.