Incidence and frequency of prostate cancer

Prostate cancer is one of the most frequent diseases in males, representing about 15% of all cancers diagnosed in men. It rarely occurs under the age of 45.

The incidence, that is the number of new cases in a given period of time, is continually growing and has doubled in the last 10 years, due to the increase in the population’s average age and the introduction of the PSA (Prostate Specific Antigen) examination. Contrary to the increasing incidence, mortality is constantly reducing, confirming the decisive role played by early diagnosis through spontaneous screening based on PSA dosing and urological consultation.

Causes and risk factors of prostate cancer

To date, causes of prostate cancer are unknown, however some potential risk factors can be identified that could promote its onset.

• Age. Age is the main risk factor for this cancer as it rarely occurs in men under the age of 45. Chances increase with age and, in our experience, the majority of men with prostate cancer are older than 60.
• Family history. For a man, the risk increases if his father or brother have a clinical history of prostate cancer.
• Race. Prostate cancer is more common in African American men compared to white people, including people of Hispanic origin. The frequency is also lower in Asian men, and Native Americans.
• Diet. A few studies suggest that men following a diet rich in animal fat or meat may be more exposed, and likewise men following a diet rich in fruit and vegetables appear to be at a lower risk.
• Genetic and hormonal factors. Mutations of certain genes, such as BRCA1 and BRCA2 or HPC1, more frequently detected in subjects aged less than 55, as well as high levels of testosterone and IGF-1 may increase the risk.

There is no specific primary prevention for prostate cancer even if there are a few behavioural rules that may be included in everyday life, such as increasing consumption of fruit, vegetables and whole grains, as well as reducing red meat and foods rich in unsaturated fats. It is good practice to maintain normal weight and keep fit by doing regular physical activity.

The majority of prostate cancers are currently diagnosed before the development of symptoms through spontaneous screening based on PSA evaluation and urological consultation.

Diagnostic pattern for prostate cancer

The diagnostic pattern for prostate cancer includes:

• PSA, PCA3, PHI dosing (prostate health index)
• digital rectal examination (urological consultation)
• prostate biopsy

Staging can be completed by:

• Multiparametric magnetic resonance
• Abdominal and pelvis CT using contrast agent
• bone scintigraphy

Nutritional prevention of prostate cancer

In addition, some nutritional recommendations. Based on a careful evaluation of the results from the scientific research, it has been possible to identify specific risk factors and protective nutritional factors for specific types of cancer. Experts have classified the results into four levels: "convincing evidence", "probable evidence", "limited evidence" and one last level that collects the effects for which evidence of association with the tumour is “highly unlikely." Probable and convincing evidence forms the basis of the recommendations.

With regard to prostate cancer, a diet too rich in calcium is a probable risk factor. The consumption of lycopene-rich foods, such as tomatoes, pink grapefruit, watermelon, and foods rich in selenium, found mainly in fish, represent a probable protective factor.

At the European Institute of Oncology, we have a specialised team for the diagnosis and treatment of prostate cancer that integrates medical and nursing competencies to guarantee 360° disease management to the patient, who is at the centre of the therapeutic process with an active role at each step.

Therapeutic approach to prostate cancer (surgery, radiotherapy and active surveillance)

Prostate cancer treatment has different goals depending on the extension and aggressiveness of the disease, the patient’s life expectancy and the presence of concomitant diseases that may represent a risk of death greater than that of the prostate disease itself.

In order to select the appropriate treatment, the patient diagnosed with prostate cancer is evaluated by considering the prognostic factors related to cancer:

• clinical stage
• Gleason score biopsy
• PSA levels
• age
• comorbidities
• life expectancy.

Localised prostate cancer can be treated with surgery (prostatectomy is currently the most widely used treatment), radiotherapy, or active surveillance (in accordance with the criteria of the International PRIAS Programme). This approach involves the simple monitoring of the course of the disease evaluated by periodic repetition of PSA dosing and prostate biopsies, integrated at our centre by multiparametric MRI.

For patients eligible for radical treatment with curative purposes, the European Institute of Oncology offers Robot-assisted surgery, that achieves great results in terms of tumour eradication, a limited perioperative morbidity having little impact on patient quality of life, and an earlier recovery of functional outcomes compared to traditional surgery.

The use of prostate multiparametric MRI and the introduction of the PI-RADS assessment system, as published by ESUR, have proved to be of considerable support in setting up surgical planning, allowing for the identification of where the tumour is most likely located and running intraoperative analysis, thereby favouring reduction of positive surgical margins.

Hormonal therapy of prostate cancer (including metastatic prostate cancers or locally-advanced cancers)

Testosterone produced by the male testes stimulates the growth of prostate cancer. Hormone therapy tries to counteract this action by slowing down or blocking testosterone synthesis (androgen deprivation).

Indications to hormonal therapy may be:

1. definitive form of therapy in metastatic or locally-advanced tumours;
2. treatment with "neoadjuvant intent" before radical intervention with the aim of increasing the proportion of negativity of surgical margins and reducing the volume of the prostate gland to be removed; before and during radiotherapy especially in patients with large tumour volume;
3. after curative surgery or radiotherapy, of prolonged or ultimate duration in high-risk patients in order to reduce the risk of disease recurrence.

Hormonal treatment can be carried out with different strategies:

• surgical removal of both testicles (bilateral orchiectomy) allows us to achieve the best results in the shortest time, permanently reducing the circulating testosterone levels. Obviously, from a psychological point of view, this approach is difficult for the patient to accept, which is the reason that nowadays, unless the patient himself prefers this drastic solution for avoiding constantly receiving treatments, surgery is reserved for urgent cases, where it is necessary to quickly lower testosterone levels in order to reduce bone metastases compression on the spinal cord (spinal compression).
• Pharmacological therapy with different types of drugs that can reduce testosterone levels in the blood, such as:

-       LHRH agonists (or GnRH) (gonadotropin-releasing hormone)

-       LHRH antagonists (or GnRH) (gonadotropin-releasing hormone)

-       Anti-androgens

Based on the patient and the disease characteristics, doctors may prescribe one of these drugs in isolation or in a combination of the two (for example LHRH agonists with anti-androgens to prevent the so-called "tumour flare"). The treatment may be continuous or with short interruption periods (intermittent therapy), to reduce the impact of side-effects.

Therapy of castrate resistant prostate cancer

Prostate cancer may progress with increasing PSA, in the absence of remote disease or with the onset or progression of metastases during or after the classic hormone therapy. These cases are called castrate-resistant prostate cancer. In this phase of the disease, the tumour is also able to grow and progress in the presence of low doses of circulating testosterone.

The first-line drug currently used in this phase is docetaxel, which has shown its contribution to increasing survival by a few months in patients treated. The approval or clinical evaluation of several new agents such as cabazitaxel, abiraterone, enzalutamide, sipuleucel-T and radium-223 have significantly changed the management of patients with metastatic castrate-resistant prostate cancer before or after docetaxel-based chemotherapy. All of these agents have demonstrated a significant survival benefit compared to their control groups.

Responses to treatment may vary depending on the associated comorbidities, extension and biological aggressiveness of the disease. The side-effects associated with treatment differ between drugs.

Treatment of bone metastases of prostate cancer

Bones are the predominant and sometimes the only sites of remote metastases of prostate cancer. Therefore specific treatment of bone metastases in prostate cancer plays a very important role, and is aimed at controlling pain, and preventing skeletal complications. The treatments of bone disease use drugs such as bisphosphonates, among which the most powerful currently available on the market is Zometa.

Denosumab is a fully human monoclonal antibody, an inhibitor of the RANKL protein ligand, that acts by inhibiting the maturation of osteoclasts and protecting bone from re-absorption, which is the cause of skeletal damage. This drug was recently approved by regulatory bodies, including AIFA (Italian Medicines Agency), for the prevention of skeletal events in patients with cancer and bone metastases.