Prostate cancer

Epidemiology and Prostate Cancer risk factors

Prostate cancer is currently the second most common cancer worldwide and accounts for about 15% of all diagnosed malignancies. The main risk factor is age. Prostate cancer is rare in men younger than 40 years of age, but it becomes more common with increasing age (the average age at the time of diagnosis is 65 years). Many factors play an important role in the onset of this disease such as family history, Westernized diet, race and lifestyle.

Prostate Cancer Diagnosis: PSA, PHI, Multi-parameter Prostatic Magnetic Resonance Imaging and Prostatic Fusion Biopsies (Fusion)

The diagnosis of prostate cancer is more frequently incidental, since it is asymptomatic in most cases. For this reason, it is advisable to undergo a digital rectal examination (DRE) after the age of 40 (a minimally invasive procedure that allows the Urologist to evaluate size, shape and firmness of the prostate) and a blood test aimed at evaluating the PSA (Prostate Specific Antigen). After 50 years of age, a PSA level below 2 ng / mL (nanograms per milliliter) is generally considered normal, whereas a PSA above 2 ng / mL deserves attention. Yet, blood PSA levels can vary for multiple reasons other than cancer (mainly benign prostatic hypertrophy and prostatitis). Thus, in case of high PSA, it is necessary to undergo more detailed diagnostic tests.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate

Magnetic resonance imaging of the prostate represents a particular type of MRI examination, which involves the acquisition of multiple images of the prostate gland. Each of these image sequences provides different anatomical, structural and functional information. In addition to the morphological evaluation of the prostate gland and surrounding anatomical structures (T2 sequences), two other parameters must be recorded: Diffusion (map of the density of prostate cells, which increases in the case a tumor is present) and Perfusion (study with contrast media that defines a map of vascularization of the prostate, which increases in the case of neoplasms). For prostate mpMRI, specific instruments are necessary, such as latest generation MRI machines, operating at high magnetic field intensity (at least 1.5 Tesla), and with dedicated hardware and software. Given the complexity of the exam, international guidelines suggest that mpMRI reporting adheres to the PI-RADS scoring, which allows for an objective evaluation of prostatic lesions, assigning them a score ranging from 1 to 5. This score represents the probability that the lesion harbors aggressive prostate cancer; the higher the PIRADS score, the higher the probability that the suspicious area is a malignant tumor. The mpMRI is now considered the most effective method for prostatic imaging as it is capable of obtaining excellent results in identifying significant prostate tumors. In this regard, international literature reports an accuracy of mpMRI ranging from 84% to 90%. The prostatic MRI has a high negative predictive value (94%), which means that if the examination is negative there is a high probability of not having an aggressive prostate cancer. These results have been confirmed by various scientific data produced also at the San Raffaele Hospital.

Prostate biopsies: targeted with fusion technique

The standard biopsy technique involves performing prostate biopsies under ultrasound guidance, through systematic sampling on the different area of the gland. This does not allow for targeting the area that is suspicious for cancer on imaging and it is mainly due to the low ultrasound accuracy of identifying cancer. The limits of the standard biopsy technique are therefore represented by the possibility of non-sampling or only partial sampling the suspicious lesions, and the possibility of sampling non-significant lesions. A solution to these problems is given by the “fusion” biopsy technique, which allows for the combination of MRI images to ultrasound images in order to target the suspicious areas. For the execution of the “fusion biopsy”, the ultrasound images obtained in real time.

Prostate Cancer Treatment in Centers of Excellence: Robotic Radical Prostatectomy, Radiotherapy, Active Surveillance and Focal Therapies

Once prostate cancer has been diagnosed, the Urologist will help in deciding which treatment is more appropriate among: active surveillance, focal therapy, robotic surgery, radiation therapy, chemotherapy, cryosurgery, hormone therapy, or a combination of these.

The use of the robotic platform for prostate cancer

The most common treatment for prostate cancer is robotic surgery which consists in the complete removal of the prostate gland, the seminal vesicles and, where indicated, the regional lymph nodes. Unlike open surgery, the robotic approach allows the Urologist to operate with a visual magnification of up to about 20 times with a 3-dimensional view. This provides the surgeon with the knowledge of the depth of field. This represents a major advantage when comparing, for example, the robotic to the classic laparoscopic technique. The intraoperative vision of the robotic system allows one to recognize even the smallest anatomical details and to perform the operation with a significantly higher accuracy than can be obtained with classical open surgery or with laparoscopic surgery. Thanks to these advantages it is possible to obtain oncological outcomes that are comparable to the open surgery, while ensuring a better and faster functional recovery. In addition, hospitalization, recovery and blood loss are significantly lower. The intervention, in most cases, is curative in the presence of localized disease and sequelae such as urinary incontinence and erectile dysfunction are very rare today. Ejaculation is always lost. However, thanks to the nerve-sparing technique that preserves the nerves responsible for erectile function, most patients who undergo this operation can quickly recover both urinary continence and erectile function.

Focal therapy for prostate cancer: brachytherapy, cryotherapy, HIFU and other treatments

Focal therapy is an emerging therapeutic alternative for those patients who, after careful selection, are eligible for this treatment. The purpose of focal therapy is to treat selectively the primary cancerous lesion, preserving the healthy surrounding tissue and important structures such as the urethral sphincter and neurovascular bundles. This reduces the morbidity related to the procedure itself, such as urinary incontinence and erectile dysfunction. The treatment can be addressed solely to the suspicious lesion (focal treatment), or, more frequently, to the area containing the lesion, or to the entire prostate lobe (hemiablation). The energy sources that can be used for this purpose are various:

• cryotherapy
• brachytherapy
• focused ultrasound (HIFU)
• photodynamic therapy
• laser
• radio frequency

The first three are the most frequently used and for which more research data are available. Patients’ follow-up involves not only over time monitoring of the treated area, but also of the rest of the gland through periodic titration of PSA, multiparametric MRI and prostate biopsy .

It has to be stressed, however, that according to the most recent European guidelines on prostate cancer, focal therapy still represents an experimental approach. Therefore, this option must be considered within prospective research studies.

Radiation therapy for the treatment of prostate cancer

Radiation therapy is a type of therapy that uses ionizing radiation, generally X-rays, for the treatment of the tumor. Such radiation works by affecting and destroying cancer cells. This, at the same time aims to spare the surrounding healthy tissues. Radiation therapy in patients with prostate cancer has a role in the following situations:

• Treatment of primary cancer
• Adjuvant radiotherapy in patients with locally advanced cancer
• Salvage radiotherapy for biochemical recurrence
• Palliative radiotherapy in metastatic patients

According to the case and the characteristics of the patients, these radiotherapy modalities can be offered: 

• Latest generation TOMOTHERAPY capable of creating image-guided modulated intensity irradiation (IMRT-IGRT)
• Volumetric intensity modulated radiotherapy RAPID ARC (IGRT)
• CYBERKNIFE
• Low dose brachytherapy by inserting radioactive seeds for the treatment of carcinoma

localized prostate

Follow-Up: Early Diagnosis and Treatment of Relapse 

After treatment, it is still necessary to carry out periodic PSA tests in order to identify any recurrence. In the case of a rise in post-treatment PSA, there are different types of therapeutic approaches, such as local radiation therapy, hormonal treatment or a combination of them.

PET for prostate cancer: choline or PSMA

The most used PET radiopharmaceutical for prostate cancer is Choline. Choline PET can be useful for staging. Yet, the main field of application of this method is represented by the evaluation of men who have already been treated for prostate cancer and have experienced a progressive increase in PSA. The use of PET / CT with Choline in this phase (disease re-staging) has the advantage of examining all body areas where disease recurrence might have occurred and to identify the recurrence site(s) with high diagnostic accuracy.

Presently, the PET / CT method with PSMA is also available. While this is still an experimental radiopharmaceutical, it has to date provided encouraging results for staging and re-staging of men with prostate cancer.

Survival in prostate cancer

Prostate cancer has a prognosis that varies depending on the characteristics of the patient and the disease itself. While a conservative approach can be considered in patients at low risk of recurrence, some men might benefit from a more radical surgical approach along with additional therapies such as radiation therapy and hormone therapy. Prof. Montorsi has been researching on the development of predictive models for the stratification of patients with prostate cancer. These tools, based on the characteristics of the patient and the disease itself, allow the doctor to predict the natural history of the disease and to identify the subjects who can benefit the most from certain therapeutic approaches. The predictive models can help the doctor in different phases of the natural history of the disease:

• Before surgery
• Immediately after the surgery
• In the event of a rise in PSA values
• after the surgery

Preoperative models: nomograms and predictive models

The therapeutic path after the diagnosis of prostate cancer is established, is based on information such as patient’s age and any comorbidities and characteristics of the disease itself. This data is used to plan the subsequent surgical strategy. The selection of candidates for pelvic lymphadenectomy represents an example of the use of these data. 

Pelvic lymph nodes represent the first site of extra-prostatic cancer invasion and harbor cancerous cells in about 10% of cases. Lymphadenectomy is the optimal method for detecting the presence of lymph node metastases. The choice of whether or not to remove the lymph nodes is determined by the risk of lymph node invasion, calculated using models based on preoperative information. Prof Montorsi and his collaborators have developed and updated over the years the most used nomogram in Urology for the identification of patients who must undergo the removal of lymph nodes. This tool, initially published in 2007 and called the Briganti nomogram, shows high predictive values in identifying patients at risk of lymph node invasion; this at the same time reduces the removal on lymph nodes, when not indicated.

Postoperative models in patients with recurrence after surgery: the risks of metastasis and the probability of survival

About 30% of patients treated with radical prostatectomy are at risk of developing recurrence, even for years after surgery. The periodic control of the PSA allows the Urologist to identify early the subjects with a biochemical recurrence (increase of the PSA values), even in the absence of symptoms. While some patients may have an “indolent” relapse, which does not expose them to the risk of developing metastases, others might benefit from additional therapies to improve long-term outcomes and prevent disease progression.