Prostate cancer

1. What is prostate cancer?

Prostate cancer is one of the most common malignant neoplasms in men. The vast majority are prostate adenocarcinoma.

An important feature is its great biological variability: there are small, very slow-growing tumors that can remain for years without causing clinical problems, and at the other extreme there are aggressive tumors capable of invading neighboring structures and developing metastases.

2. Risk factors

2.1 Age. It is one of the most important factors: incidence increases significantly with age.

2.2 Family history. Risk increases when first-degree relatives have prostate cancer, especially when several relatives are affected or the diagnosis occurred at a young age.

2.3 Genetics. Some hereditary alterations increase the risk of prostate cancer and may be associated with more aggressive forms. An important example is certain pathogenic variants of BRCA2. Genetics is becoming increasingly important both for assessing hereditary risk and for selecting treatments in certain patients with advanced disease.

3. Clinical presentation: what symptoms does it cause?

3.1 Localized disease. This is one of the most important concepts for the student: localized prostate cancer is generally asymptomatic. Many patients are diagnosed because of an abnormal PSA and/or a suspicious digital rectal exam, without having any symptoms.

3.2 What about urinary symptoms? A patient may consult for a weak stream, difficulty initiating urination, nocturia, frequency, urgency or a sensation of incomplete emptying. But these symptoms are extremely common in older men and are usually related to benign prostatic hyperplasia or other lower urinary tract disorders.

3.3 Advanced disease. When the disease is advanced, bone pain, hematuria, urinary obstruction, weight loss, anemia and general deterioration may appear. Bone is one of the main sites of metastasis of prostate cancer.

4. PSA: what it is and what it means

4.1 What is PSA? PSA stands for prostate-specific antigen: it is a protein produced by prostate cells. There is a fundamental difference: PSA is specific to the prostate, not to cancer. An elevated PSA does not automatically mean that cancer is present.

4.2 Why can PSA rise? It can be elevated in different situations: prostate cancer, benign prostatic hyperplasia, prostatitis, urinary tract infection, urinary retention or certain urologic manipulations. PSA is a tool for estimating risk.

4.3 Is there a "normal" PSA? We should not simply interpret PSA as normal/abnormal: cancer risk lies along a continuum. Interpretation must take into account age, PSA value, previous trend, prostate volume, digital rectal exam, family history, comorbidities and life expectancy. An isolated value should not be interpreted outside the clinical context.

5. PSA density

A very useful concept is PSA density, which is calculated as PSA ÷ prostate volume.

The same PSA can represent different risks depending on prostate volume.

6. Digital rectal exam

The digital rectal exam allows assessment of prostate consistency, the presence of nodules, induration, asymmetries and general characteristics of the gland. Suspicious findings are: a hard nodule, induration or marked irregularity. A suspicious digital rectal exam requires urologic evaluation.

7. From suspicious PSA to biopsy: the role of MRI

7.1 Do we go straight to biopsy? In general, the contemporary approach is not to go automatically from PSA to biopsy. First we must better estimate the risk of clinically significant cancer. At this point, multiparametric prostate MRI becomes very important.

7.2 Multiparametric MRI. MRI can identify suspicious lesions, determine their location, estimate the probability of clinically significant cancer, guide the biopsy and provide information on local extent. Lesions are usually reported using PI-RADS.

7.3 What does PI-RADS mean? In simplified terms: PI-RADS 1, very low suspicion; PI-RADS 2, low suspicion; PI-RADS 3, indeterminate finding; PI-RADS 4, high suspicion; PI-RADS 5, very high suspicion.

8. Prostate biopsy

8.1 Types of biopsy. When the risk justifies obtaining tissue, a prostate biopsy is performed, which may include targeted biopsies (samples taken specifically from the lesions identified on MRI) and systematic biopsies (samples taken following a predetermined distribution across different prostate sectors). The strategy is adapted to the clinical scenario.

8.2 What does the biopsy tell us? The biopsy allows us to answer: is there cancer? What type of cancer? What grade is it? And how much tumor is seen? Pathology is essential for estimating the aggressiveness of the disease.

9. Gleason and Grade Group

9.1 Gleason score. Prostate adenocarcinoma shows different architectural patterns. The pathologist identifies the predominant patterns and traditionally expresses them using the Gleason score, for example: Gleason 3+3 = 6, Gleason 3+4 = 7, Gleason 4+3 = 7, Gleason 4+4 = 8.

9.2 Gleason 3+4 is not the same as 4+3. Although 3+4 = 7 and 4+3 = 7, they do not represent exactly the same biological behavior: in the latter, pattern 4 predominates, which is associated with greater aggressiveness.

9.3 Grade Group. It is now common to also express the grade using the Grade Group:

Put simply: the higher the Grade Group, the greater the aggressiveness.

10. Staging and risk classification

10.1 We have diagnosed cancer, now what? Now we must answer two different questions: how aggressive is it? And how far has it spread? To do this we combine PSA, Grade Group, clinical stage, volume and tumor characteristics, plus staging studies when appropriate.

10.2 Staging. Conceptually, we can divide the disease into localized (the tumor remains within the prostate), locally advanced (there is extension beyond the prostate and/or involvement of regional structures) and metastatic (there is distant disease). The particularly important sites are the lymph nodes and bone.

10.3 Risk classification. Two patients with "prostate cancer" can have completely different diseases.

Both have prostate cancer, but their risk, prognosis and treatment are very different. That is why treatment is established according to risk group, and not simply by the presence of cancer.

11. Treatment strategies: general concepts

There are four big concepts the student must know: monitor, operate, irradiate and treat systemically. The choice depends on the tumor and the patient.

12. Active surveillance

Some prostate cancers have a very low risk of progression. In properly selected patients we can offer active surveillance: monitoring the disease through a protocol that may include PSA, clinical evaluation, MRI, biopsies or other tests when indicated. If signs of progression appear, curative treatment can be indicated.

13. Radical prostatectomy

13.1 What it involves. It is one of the curative treatment options for localized disease in selected patients. It essentially consists of removing the prostate + seminal vesicles, and then reconstructing urinary continuity through a vesicourethral anastomosis. It can be performed by open, laparoscopic or robot-assisted surgery; the surgical approach does not change the fundamental oncologic principle of the operation.

13.2 Adverse effects. Two aspects are particularly important: urinary incontinence and erectile dysfunction. The risk depends on multiple factors: age, baseline function, tumor characteristics, anatomy, the possibility of neurovascular preservation and surgical technique. That is why these aspects must be discussed before treatment.

14. Radiotherapy and hormonal therapy

14.1 Radiotherapy. It is another potentially curative strategy for many patients with localized cancer and can be delivered through different modalities. In certain risk groups it is combined with androgen deprivation therapy. The choice between surgery and radiotherapy should not be reduced to saying that one is universally "better": it depends on tumor characteristics, age, comorbidities, expected adverse effects and patient preferences.

14.2 Why does hormonal therapy work? Prostate cancer cells depend heavily on androgen signaling. That is why we can reduce the hormonal stimulus through androgen deprivation therapy, one of the pillars of treatment for advanced disease, which is also combined with radiotherapy in certain higher-risk localized disease scenarios.

15. Metastatic disease

When there is metastatic disease, we are no longer treating only the prostate: we are treating a systemic disease. Modern treatment may combine androgen deprivation, drugs targeting the androgen receptor pathway, chemotherapy, radiotherapy in certain scenarios, treatments targeted to molecular alterations and radiopharmaceuticals in selected patients. The selection depends on the clinical scenario and the characteristics of the tumor.

16. PSMA PET

PSMA is a protein that is usually expressed in prostate cancer cells. PSMA PET/CT can detect prostate disease in certain scenarios with high sensitivity. It has especially important applications in the staging of certain higher-risk patients, the evaluation of recurrence and the selection of certain PSMA-targeted therapies.

17. Biochemical recurrence

After treatment with curative intent, PSA remains a fundamental tool. A rise in PSA may be the first sign of recurrence before disease is visible on conventional imaging: this is called biochemical recurrence. Subsequent management depends on the initial treatment, tumor characteristics, PSA kinetics and the location of the disease.