Prostate cancer

What is prostate cancer ?

Prostate cancer is the most common cancer in men in France, with over 59,000 cases and 8,100 deaths per year in 2018. Age strongly impacts the risk, with highly variable prognoses.

While diagnosis often occurs at a localized stage, there are aggressive forms that are metastatic from the outset. Overall, the 5-year survival rate is over 90%. It primarily affects older men, with a median age at diagnosis of 69 years. Prostate cancer cells derive from epithelial cells of the prostate.

These cells secrete PSA, levels of which are part of the screening for this disease and are also crucial for its long-term monitoring. Androgens, particularly testosterone, stimulate the growth of tumor cells.

Therefore, prostate cancer is considered a hormone-dependent cancer, similar to certain types of breast and endometrial cancers. It's worth noting that there are hereditary forms predisposed to prostate cancer, particularly in cases of BRCA2 gene mutations.

Interview with Professor Thierry Lebret

Il existe plusieurs histologies (type de tissu atteint) de cancer de la prostate :

• The most common (>95% of cases), which we will discuss here, is prostatic adenocarcinoma.
• There are also neuroendocrine carcinomas, much rarer, which are managed with surgery or chemotherapy in cases of advanced disease.

When discussing prostate cancers, it mainly concerns different presentations of the disease :

• According to the extent of cancerous lesions :

- Localized : confined to the prostate gland.

- Regionally advanced : extending around the prostate gland but not beyond the pelvis.

- Metastatic : cancer that has spread to other parts of the body. Prostate cancer cells often migrate to bones and lymph nodes, but visceral involvement (liver, lung, and rarely brain) is also possible.

• According to treatment response :

- Hormone-sensitive forms : responsive to first-line hormonal or chemical castration.

- Castration-resistant forms : which do not respond to initial castration (primary resistance) or progress after an initial response to hormonal treatment (secondary resistance).

Causes and risk factors

The main risk factors for prostate cancer are :

• Age
• Endocrine disruptors (such as chlordecone)
• Family history

Screening

Screening is crucial due to the asymptomatic nature of this cancer. There is no organized screening program, so it is important to monitor the prostate and, if necessary, conduct further investigations to determine if biopsies are needed.

PSA or Prostate-Specific Antigen is an indicator of specific prostate activity. Annual PSA monitoring begins at age 50, or earlier in at-risk families.

An initially high level or a continuous increase in this marker warrants further prostate exploration. These investigations are based on clinical examination (digital rectal exam to check for prostate hardening) and prostate MRI (presence of suspicious areas according to international criteria). In case of a pacemaker, a contrast ultrasound can replace the MRI.

Prof. François Desgrandchamps, Professor of Urology at Université Paris Cité and Research Director at the Atomic Energy Commission (CEA) and Head of the Urology Department at Saint-Louis Hospital AP-HP :

"There are two voices that are heard, the national voice of the Haute Autorité de Santé which simply says that we do not screen, which means that it is a bit too complicated to meet the national demand so we prefer to say no. Rather than what the French Association of Urology does, which is the other voice that is heard, saying that screening should be done individually. By informing patients from the start that if we screen and find a cancer that is not dangerous in the long term, we may not treat it and it will not need to be treated. So, the position on screening is ambiguous because prostate cancer is not one single disease but two different diseases. A benign one that we do not treat and another that needs to be treated."

Interview with Professor François Desgrandchamps

Symptoms

Prostate cancer is most often asymptomatic. Depending on the stage of the disease, the symptoms are different.

At the localized stage

Symptoms may appear but are not specific and can be related to other non-cancerous prostate conditions such as benign prostatic hyperplasia (prostatic adenoma, "enlarged prostate" related to age) or prostatitis (inflammation/infection of the prostate).

Common urinary symptoms at the localized stage include :

• Dysuria: Difficulty urinating with decreased urinary flow
• Pollakiuria: Frequent urination, nocturnal awakenings
• Urinary urgency: Urgent need to urinate
• Acute urinary retention: Inability to urinate
• Macroscopic hematuria: Blood in the urine
• Hematospermia: Blood in the semen

At the metastatic stage

The disease most often manifests through bone symptoms (main metastatic site) :

• Bone pain
• Spinal cord compression with back/lower back pain
• Incontinence issues
• Motor deficits in the lower limbs
• General symptoms with a decline in general health: unusual fatigue, weight loss

Diagnosis

Seules les biopsies de la prostate réalisées dans les meilleures conditions, éventuellement en ciblant par fusion d’image les zones suspectes en IRM, permettent de faire correctement le diagnostic.

Furthermore, assessing the cancer's aggressiveness relies on the Gleason score, which is determined by examining biopsy samples and ranges from 6 (good prognosis) to 10. The size of the cancer is also a prognostic factor, evaluated based on MRI data and the length of cancer infiltration in the biopsies.

The quality of the initial diagnosis influences the choice of therapeutic options and subsequent outcomes. Moreover, the search for extraprostatic extension depends on the cancer's aggressiveness. Bone scintigraphy and CT scans, or sometimes positron emission tomography (PET-Scan), are indicated, especially in locally advanced forms.

Treatments

When a low-aggressiveness cancer minimally affects the biopsies, active surveillance may be proposed, with reevaluation through MRI and biopsies within the first year, with the necessity of treatment in case of progression.

Localized cancer

In cases of localized prostate cancer that may potentially progress, several options are available: surgery or radiotherapy. There are situations where both treatments are feasible, and in such cases, the patient should participate in the treatment choice.

Prostatectomy

Surgery involves prostatectomy, which consists of removing the prostate, seminal vesicles, and, if necessary, the nearby lymph nodes draining the prostate.

Prostatectomy is indicated for localized forms but becomes more debatable in locally advanced forms with seminal vesicle invasion and/or lymph node involvement.

The main long-term complications of the surgical procedure are incontinence, whose frequency has significantly decreased with the improvement of surgical techniques, and sexual disorders, particularly erectile dysfunction.

Surgical techniques are equivalent, whether in conventional surgery or laparoscopic surgery, possibly robot-assisted.

Radiotherapy

Radiotherapy involves defining a treatment volume that includes the prostate and, if necessary, the seminal vesicles and lymph node areas. This volume undergoes fractionated irradiation with intensity modulation, with the number of sessions depending on the initial stage.

The prostate is localized at each session, and irradiation is delivered from multiple angles to protect neighboring organs. Finally, in aggressive forms, hormone therapy may be added to reduce the risk of recurrence.

Other localized treatments

Other localized treatment options may also be considered, including brachytherapy, focused ultrasound, and other less developed techniques. Thus, it is not always easy for the patient to decide, and a second opinion may be necessary. Comprehensive information is essential for the patient to participate in the therapeutic choice without future regrets.

Regardless of the treatment, recurrence is possible, manifested by an increase in PSA levels. A PET scan with fluorocholine or PSMA can determine if it is a localized recurrence accessible to new local treatment.

In case of recurrence after prostatectomy, radiotherapy may be proposed.

In case of recurrence after radiotherapy, therapeutic choices are not standardized. Prostatectomy can be considered, but its consequences may be more severe. Other treatments offered include stereotactic radiotherapy focused on the recurrence, brachytherapy, or other treatments such as focused ultrasound, cryotherapy, etc.

Some recurrences in the lymph nodes or bones are accessible to radiotherapy.

Metastatic cancer

In cases of metastatic prostate cancer, the treatment is based on hormone therapy. This involves pituitary stimulation aimed at stopping testosterone production by the testes, possibly combined with an anti-androgen.

In some cases, chemotherapy or immunotherapy may be considered. For these metastatic forms, local treatment of the prostate with radiotherapy can be beneficial for improving survival. Additionally, new hormone therapies have significantly improved survival in advanced cases.

Endoscopic surgery is sometimes necessary to clear the prostatic urethra or reopen the ureters in certain locally advanced forms.

As with all cancers, the chosen therapeutic option must be validated in a multidisciplinary consultation meeting.