Urology Sbobine 1-6 PDF

# Lezione 1 ## Urology Introduction ### General Information About the Course The professor states that he doesn't want to teach urology because probably no one of us will want to become a urologist but he rather wants to transmit the passion for medicine and surgery. However, he states that the most...

# Lezione 1 ## Urology Introduction ### General Information About the Course The professor states that he doesn't want to teach urology because probably no one of us will want to become a urologist but he rather wants to transmit the passion for medicine and surgery. However, he states that the most amazing and complete specialty for him is urology and he will try to demonstrate that through his lessons. ### Textbook The professor will provide a QR code in the slides. The recommended book is "Smith and Tanagho's general urology". He will also provide the Italian version in his slides which he recommends using especially for looking at the images, from radiologies to interoperative pictures. However, no extra information will be asked in the exam, which he claims to be "extremely easy" since only basic knowledge will be required. He also talks about the possibility of a pre-examination *in itinere*. ### Urology Introduction And Patient Evaluation Urology is a specialty which has both medical and surgical implications in diseases of the urinary tract system and reproductive organs. - **Kidneys and Adrenal Glands**: stones, cancers, congenital diseases. - **Ureters**: stenosis, stones, cancers. - **Bladder**: including incontinence, infections. - **Urethra**: stenosis, cancer. - **Male Reproductive Organs**: testes, epididymis, *vas deferens*, seminal vesicles, prostate, and penis. During the evaluation of an urologic patient, a physician needs to first evaluate the patient rather than the disease. The collection of data and history of the patient is a crucial step in the diagnostic process. - Afterwards, the physical examination should performed to avoid unnecessary invasive exams. The abdominal and rectal examination are the most important in this field. - An accurate *anamnesis* and physical examinations can lead to a complete understanding of the situation of the patient and only after defining a possible diagnosis we can select the best optimal laboratory and radiological exam. For example sometimes there can be a patient with two different diseases but the exams may only show one of these, while through *anamnesis* we can understand possible symptoms related to the second condition. # Lezione 2 ## Symptoms of Urology ### The Use Of Guidelines When reviewing the guidelines on prostate cancer, we see that a patient may present with symptoms, or sometimes none at all. The guidelines allow us to choose among different treatment options: medical, radiotherapeutic, or surgical, each with varying outcomes. However, the natural history of the disease can be complex, as patients are often not fully aware of their condition. So we must identify the correct guidelines and the best diagnostic pathway to arrive at an accurate diagnosis, adapting our knowledge to daily clinical practice. The guidelines by the European association of urology (EAU) are a fantastic tool, not only for the treatment, since identifying the correct therapeutic pathway is very complex, but also for diagnosis of urological conditions. However they need to be adapted to the different situations. ### Symptoms In Urology #### Lower Urinary Tract Symptoms - Hematuria - Urinary incontinence - Pain - Sexual dysfunction The most common urological symptoms reported by patients involve the lower urinary tract (urinary bladder and its outlet). - **Storage Symptoms**: urinary infections or inflammation of the bladder walls. - increased frequency and urgency of passing urine. - urge incontinence - needing to get up to pass urine at night - **Voiding Symptoms**: an enlarged prostate may cause difficulty in completely emptying the bladder. - hesitancy (delay in initiating urination), - intermittent stream (starting and stopping flow), - straining, - terminal dribbling. - **Post-Voiding Symptoms**: the sensation of incomplete bladder emptying. ### International Prostate Symptom Score (IPSS) Urinary symptoms can be quantified using tools such as the International Prostate Symptom Score (IPSS) questionnaire, which assigns numerical values to the severity of symptoms. In patients unable to clearly articulate their condition, visual questionnaires may be employed. These kinds of questionnaires can be employed with neurological patients or patients with sexual disorders. # Lezione 3 ## Main Urinary Symptoms ### Hematuria Hematuria is defined as the presence of blood in urine. It is a quite concerning urological sign, as in about 1/4 of the patients complaining this symptom the cause is found to be a urologic cancer. For this reason, patients with hematuria need to be cautiously studied, considering also that it's not uncommon for them to deny this symptom. #### Types Of Hematuria - **Microscopic Hematuria**: when the presence of blood is not visible by naked eye. - **Macroscopic or Gross Hematuria**: when urine is visibly discolored by blood. - **Pseudo-hematuria**: the sole presence of red-colored urine is not always the result of blood. The color can occur for example in patients under diuretic restriction, mimicked by the color of concentrated urine, or due to the intake of some drugs like Rifampicin. [also, some foods can cause it] - **Urethrorrhagia**: bleeding is separated from the micturition, and it means that the source of the bleeding is below the sphincter. - **Rapid Tool to Identify Hematuria**: urine dipstick, although its results are not so certain; sometimes in fact this test is subject to false positives, and so for this reason it needs to be always confirmed by *urinalysis*. #### Microhematuria As soon as MH is detected on a sample, the first thing to evaluate is its persistence on a second analysis, because its positivity on two following samples can be indicative of cancer and thus needs to be carefully evaluated. #### Urinary Tract Cancers - Smoking - Male gender - Age older than 35 years - Occupational or other exposure to chemicals or dyes (benzenes or aromatic amines) - Analgesic abuse - History of gross hematuria - History of urologic disorder or disease - History of irritative voiding symptoms - History of pelvic irradiation - History of chronic urinary tract infection - Exposure to known carcinogenic agents or chemotherapy such as alkylating agents - History of chronic indwelling foreign body In the course of the patient visit it's therefore important to not only consider the results of *urinalysis*, but also to collect a complete and proper patient's history. #### Gross Hematuria The situation here likely becomes more complex, as the amount of blood is significantly more. The first sample presents light hematuria, while the second it's much more relevant, likely from an arterial bleeding. The third picture, presenting an almost brown discoloration of the sample, is usually associated to the presence of clots, for example in the bladder. It's sometimes defined as "Coca Cola urine". #### Three Glasses Test - Sometimes the hematuria is not complete, with the bleeding only occurring in the first part of the micturition and pseudo-normal urine towards the end. - The problem is most likely problem regarding the urethra, which gets flushed by the first stream of urine. - Another situation is the one in which the entire micturition presents a red discoloration. - The third and most strange possibility is the one in which only the last drops of urine are colored by blood. This is due to a particular situation in which the bleeding occurs due to a contraction of the detrusor muscle, and it's typical of the presence of a neoplasm of the bladder wall, thus resulting the most worrisome case out of the three. In concomitance with hematuria, it is also important to analyze and ask the patient if there are other associated symptoms. For example, if the bleeding is associated to Lower Urinary Tract Symptoms [explained in the previous lecture, will be referred as LUTS from now on], especially with the irritative ones, this becomes the typical presentation of an infection: there is a bleeding resulting from the inflammation, while the presence of pathogens irritates the bladder's mucosa, resulting in a hemorrhagic cystitis. #### Causes Of Hematuria - **Pre-renal**: an overdose of anticoagulants (especially occurring in the elderlies due to improper intake). [also hypertension and sickle cell anemia, from the slides] - **Renal**: glomerulonephritis, cancer or stones in the upper urinary tract, and vigorous exercise. - **Postrenal**: bladder cancer, bladder stones, prostate cancer and a traumatic catheter insertion. #### Nutcracker Syndrome The bleeding during micturition is caused by an rare anatomical abnormality: normally the renal vein passes normally between the superior mesenteric artery and the abdominal aorta, however in this alteration the artery partially occludes the renal vein by squeezing it. The result is an increase of the venous pressure into the kidney,(which can cause hematuria by chatgpt). Of course this technique is only diagnosed through imaging such as *AngioCT*. "Summary scheme of the things you need to know about hematuria" Keep in mind that, more often than not, hematuria is a sign of neoplasm in the system, therefore it always needs to be paid careful attention. # Lezione 4 ## Benign Prostatic Hyperplasia (BPH) ### The Prostate The prostate is an exocrine gland situated inferior to the bladder and anterior to the rectum. It typically weighs approximately 20 grams and tends to increase in size with advancing age, potentially leading to clinical complications. The urethra traverses the central zone of the prostate, which is also penetrated by the ejaculatory ducts originating from the seminal vesicles. These ducts terminate at the prostatic urethra, which terminate into the external urethral sphincter. Recognizing these anatomical landmarks is crucial for surgical interventions, as damage to the sphincter can result in urinary incontinence. The prostate receives its blood supply from branches of the internal iliac artery, specifically the inferior vesical artery. Venous drainage is facilitated by the periprostatic venous plexus, also known as the Santorini plexus, which is connected to the dorsal vein of the penis. Such vessels must be carefully managed during surgery to prevent significant hemorrhage. Anatomically, the prostate is divided into five lobes: the anterior lobe, posterior lobe, median lobe (often associate with benign prostatic hyperplasia and enlargement with age), right lateral lobe, and left lateral lobe, which is continuous with the anterior lobe. This anatomical structure serves as a landmark during surgical procedures, as its proximity to the rectum poses a risk of rectal injury during prostatectomy. The urethra within the prostate is not linear but follows a curved path, which is crucial to consider in the context of urinary incontinence. The anterior aspect of the prostate is anchored to the pubic symphysis, while the bladder is secured to the anterior abdominal wall. This curvature facilitates the closure of the urethra during increases in intra-abdominal pressure, aided by the support of the pubic bone. Consequently, during prostatectomy, it is essential to reconstruct this anatomical configuration to prevent postoperative incontinence by ensuring the functional integrity of the urethral sphincter mechanism. ### Histology The prostate is composed of epithelial glands embedded within a stroma of fibromuscular and connective tissue, which includes collagen fibers and smooth muscle (SM) fibers. The presence of smooth muscle fibers is particularly significant when considering the pharmacological effects of certain medications, as these fibers play a crucial role in the contractile function of the prostate. ### Embryology The development of the prostate is a complex process that originates from the Müllerian tubercle. The prostate arises from the urethral epithelium, which is associated with the mesonephric (Wolffian) duct. This developmental relationship establishes a significant anatomical and functional correlation between the prostate and the upper urinary tract components. This connection underscores the potential for infections, as bacteria can migrate from the rectum to the urinary tract. Additionally, due to anatomical differences, females are at a higher risk of urinary tract infections (UTIs) compared to males. ### Endocrinology The prostate gland is under endocrine control, primarily regulated by testosterone. This growth is not observed in castrated dogs, which remain smaller overall. Testosterone plays a crucial role in the development of secondary accessory organs and sexual behavior. It can also increase mortality and the risk of certain diseases due to its involvement in maintaining the immune system. Testosterone has been linked to addictive behaviors, as its influence on the brain's reward system can lead to dependency on substances or activities that increase its levels. Behaviorally, testosterone is associated with increased aggressiveness. It is important to note that males also produce estrogens, which are balanced with androgens. Testosterone supports growth and development, while estrogens contribute to the fibro-stromal tissue component. Testosterone itself is not active but requires metabolic conversion by the enzyme 5-alpha-reductase to become dihydrotestosterone (DHT), its active form. Certain drugs can modulate the activity of this enzyme, thereby regulating the levels of active testosterone. This modulation can have a progressive castration effect on the prostate. ### Benign Prostatic Hyperplasia (BPH) An enlargement of the prostate gland can lead to Benign Prostatic Obstruction (BPO), mechanically obstructing the urethra and causing urinary retention. Obstruction can also occur in benign conditions, such as Benign Prostatic Enlargement (BPE) where the bladder neck closes despite a normal-sized prostate. Patients may present with similar lower urinary tract symptoms (LUTS), such as frequency, urgency, nocturia, and weak stream. Neurological causes can also produce similar symptoms. It is important to note that prostate enlargement can result in a wide range of symptoms, from severe to none. Typically, prostate enlargement progresses slowly over decades. During this time, the bladder compensates by increasing its muscular activity to maintain urine flow. Eventually, the bladder's compensatory mechanisms fail, leading to a reduced urine stream and ultimately, urinary retention. The hyperplastic process and gland hypertrophy begin in adolescence and are influenced by sex hormones. LUTS usually manifest much later, often 15-20 years after the onset of gland hyperplasia. Thus, young patients with significant gland hyperplasia may not exhibit symptoms immediately. Prostate growth often follows a nodular pattern, with progressive stretching of the peripheral zone, creating a pseudo capsule around the gland. Enlargement typically originates from the transition zone near the bladder neck, causing a mechanical obstruction. There is also a dynamic component to the obstruction due to the high density of smooth muscle fibers in the prostate, which contains alpha-adrenergic receptors. These receptors regulate the tone of the urethra, causing it to constrict under stress or strong stimulation. Under stress, increased sympathetic activity can exacerbate urethral closure, leading to acute urinary retention. Long-term obstruction affects bladder muscle contraction, leading to muscle hypertrophy and thickening of the bladder wall, which can increase from the usual 0.5 cm to 2-4 cm. Additionally, bladder capacity may be reduced. Chronic obstruction can cause the formation of diverticula, *which are herniations of the bladder mucosa due to high intravesical pressure*. Other effects include progressive bladder dilation, upper urinary tract dilation such as J-hooking of the ureters, *hydronephrosis*, and ultimately renal function impairment. Residual effects can include the formation of bladder stones, *which can be large and manifest with LUTS, hematuria, and urine retention*. Additionally, there is an increased risk of urinary tract infections (UTIs) and sepsis. ### Medical History A comprehensive medical history, conducted following established guidelines, is essential for these patients. Utilizing standardized questionnaires, such as the "EUA Guidelines of Non-Neurogenic Male Lower Urinary Tract Symptoms (LUTS), including Benign Prostatic Obstruction (BPO)", can objectively identify symptoms. These assessments should include detailed inquiries about the duration, frequency, and onset of micturition, among other factors, to obtain a complete clinical picture. ### Physical Examination Referring to the digital rectal examination (DRE) of the rectum, a thorough visual inspection and palpation of the abdomen is performed initially to evaluate for signs of bladder distension, *indicative of chronic urinary retention*. The examination is conducted using the index finger, as it is the most sensitive. During the DRE, the size, consistency, and symmetry of the prostate are assessed, along with the temperature to identify potential infections such as prostatitis. Additionally, the presence of neoplasms or other abnormalities is evaluated. ### Other Diagnosis Methods - Urinalysis: Demonstrates secondary effects of UTIs, like obstruction. - Renal Function Measurement: In case of large dilation of the upper UT, there might be a progressive impairment in renal function, secondary to chronic retention of the urine. - Prostatic Specific Antigen (PSA): A prostate cancer marker. - Uroflowmetry: a simple device that describes the quantity of urine passed in a certain period. The information is collected to form a graph, where the flow usually peaks at the beginning of the micturition (Qmax). In pathological situations, the graph changes and there is a decrease in the Qmax and prolonged urination, which happens in BPH. - Ultrasonography: easily performed in the clinic, and cheap to use, that allows one to get an anatomical picture of the situation. In this case, we can notice a larger median lobe. In this enlargement example, the impact and risk of obstruction are very high. It could also be used to assess the upper urinary tract, for example, to look at a dilation. - CT Scan: also used to better assess dilation, and fluid detection, like in the case of *urosepsis*, that could be lethal if not detected and treated. ### Differential Diagnosis 1. **Urethral Stricture** - *Definition*: A narrowing of the urethra due to scarring, results in a loss of urethral elasticity. - *Cause*: Trauma from accidents, radiation therapy, or a complex sexually transmitted infection (STI) leads to scar formation. - *Symptoms*: Elongated micturition (prolonged time to urinate). Seen in *uroflowmetry* as a lack of a peak, showing a plateau on the graph. - *Treatment*: Endoscopic surgical intervention to open the urethra. High risk of recurrence. In case of recurrence, a substitution of the stenotic part of the urethra with a portion of buccal mucosa may be performed due to its high vascularization, which promotes quick revascularization of the urethra. 2. **Marion's Disease** - *Definition*: Congenital disease is the first identified condition affecting the bladder neck, leading to urinary obstruction. - *Cause*: Contraction of the bladder neck, resulting in difficulties with micturition. - *Symptoms*: Similar to prostate enlargement, particularly obstruction to urine flow. - *Treatment*: An electric incision at the bladder neck to create an opening at the urethra and restore normal urine flow. Risk of retrograde ejaculation, where ejaculatory fluid flows back into the bladder instead of the urethra, which can affect fertility. 3. **Bladder Neck Contracture** - *Definition*: A rare condition where scar tissue forms at the bladder neck, narrowing the passage and obstructing urine flow, typically after prostate surgery or treatment. - *Cause*: Formation of scar tissue following prostate surgery or radiation therapy. - *Symptoms*: Weak or interrupted urine stream. Frequent urination. Straining to urinate. Incomplete bladder emptying. - *Treatment*: Urinary retention. Pain or discomfort. Potential for urinary tract infections due to incomplete bladder emptying. Use of catheters or dilators to widen the urethra. Surgical removal of scar tissue to restore normal urinary function. ### Prognosis Key predictors of the clinical progression of benign prostatic obstruction include: - Elevated PSA levels: While PSA is not a disease-specific marker, it is indicative of prostatic tissue. - Larger prostates produce higher PSA levels. - Increased prostate volume. - Higher baseline post-void residual (PVR). (the amount of urine retained in the bladder after micturition) Elevated markers indicate a poorer prognosis and an increased likelihood of requiring medical intervention. Male lower urinary tract symptoms (LUTS) can result from various etiologies, necessitating a thorough collection of patient information to accurately identify the underlying cause. The overall complexity of the patient's condition must also be considered. This flowchart aims to outline the steps for managing male LUTS. It is essential to consider patient-specific scenarios, such as a patient experiencing nocturia who is unable to return to sleep, significantly impacting their quality of life. ### Treatment #### Therapy In The Past Historically, many surgical interventions were performed to address prostate-related issues, with some of the earliest procedures focused on removing bladder stones. #### Therapy Evidence suggests that patients were placed in the *lithotomy position* (derived from the Greek "lithos," meaning stone), and surgeons made incisions in the *peritoneum* to access and remove the stones and use vegetables or bamboo as catheters. One remarkable case is that of Jan de Doot, who famously performed bladder stone surgery on himself with a *kitchen knife* and survived. - As a first-line treatment, behavioral and dietary modifications are recommended. For instance, patients experiencing nocturia are advised to reduce fluid intake in the evening to limit nocturnal urine production. Additionally, distraction techniques can be employed to alleviate irritative symptoms. - The second line of treatment typically includes: - **Phytotherapy**: Treatment using plant extract-based drugs, such as *Prostamol*, aimed at reducing symptoms like *nocturia* (frequent nighttime urination). - Target: Reduces prostate inflammation, though the specific mechanism isn't fully detailed. - Effects: May help alleviate mild symptoms of prostate inflammation, particularly *nocturia*. However, its effectiveness is often questioned. - **Alpha-Blockers**: Medications that relieve obstruction by relaxing muscle fibers in the bladder neck and prostate. - Target: Muscles under adrenergic control, particularly at the bladder neck, and prostate, to improve urine flow and prevent acute urinary retention. - Effects: Improves the urine stream by relaxing fibers, alleviates symptoms of obstruction, and prevents acute urinary retention. - **5-Alpha-Reductase Inhibitors**: Medications that reduce prostate size by inhibiting the enzyme responsible for converting testosterone into dihydrotestosterone, the active form of testosterone. - Target: The enzyme 5-alpha-reductase, which converts testosterone into dihydrotestosterone. - Effects: Slows prostate growth, leading to a 20% reduction in prostate volume (progressive castration) and reducing symptoms over a long-term period (6 to 12 months). ### Surgical Therapy If lifestyle changes and medical therapies prove insufficient or inappropriate, surgical interventions may be required to address prostate-related obstructions. Several advanced techniques are available today: - **Transurethral Resection of the Prostate (TURP)**: This is the oldest technique, where a resectoscope (an electric loop) is inserted through the external meatus to reach the prostate. It scrapes away the internal portion of the gland, enlarging the urethra and solving the obstruction. It's a quick procedure, but care must be taken to avoid cutting the external urethral sphincter, which could lead to incontinence. Rarely, complications like bladder explosion due to excessive gas can occur, requiring surgical repair. - **Laser Resection | Enucleation or Vaporization**: Like TURP, this technique uses a laser to remove the internal portion of the prostate. It allows precise control of bleeding and tissue removal. After the procedure, a device is used to aspirate the remaining material. The outcome is comparable to TURP, though the professor notes that high energy from the laser may cause irritative symptoms, which can be problematic. - **UroLift**: A minimally invasive option where small implants are used to lift and hold enlarged prostate tissue away from the urethra, avoiding incisions or tissue removal. This procedure improves urine flow without the risk of retrograde ejaculation, making it a good option for younger patients. - **AquaBeam | REZUM**: REZUM uses water vapor therapy, where steam is injected into the prostate through a needle to shrink the gland. Over time, this leads to necrosis and an improved urine stream. It preserves normal ejaculation and is often recommended for patients seeking to avoid sexual side effects. However, there is a risk of tissue regrowth, potentially requiring further intervention later. - **Simple Prostatectomy**: For extremely large prostates (200-300g, contrary to physiological 20g), open surgery through the abdominal wall can be performed to remove the internal portion of the prostate. Though robotic and less invasive techniques have made this approach largely obsolete, it remains an option. For elderly or frail patients, placing a catheter may be a more practical solution, helping to maintain kidney function without the risks of surgery. (NoS: https://www.youtube.com/watch?v=K1yLUyfgjpI) ### Catheter | Suprapubic Tube The most straightforward and cost-effective intervention for patients presenting with symptoms such as urinary retention or severe lower urinary tract symptoms (LUTS) is catheterization. The procedure involves the insertion of a catheter into the bladder, followed by the inflation of a balloon to secure the catheter in place. This method provides an efficient and economical means of facilitating urinary drainage and preventing retention, particularly in elderly patients or those with comorbidities who are unsuitable candidates for surgical intervention. Alternatively, catheterization can be performed via a suprapubic approach, wherein the catheter is inserted through the abdominal wall directly into the bladder. Although this method can sometimes be more uncomfortable for the patient compared to traditional transurethral catheterization, it remains a viable option. However, the use of catheterization as a long-term solution is generally limited to specific clinical scenarios. # Lezione 5 ## Prostate Cancer ### Introduction About Prostate Cancer November is recognized internationally as Men's Health Month, with particular attention given to prostate cancer. The symbol for this campaign is specific to prostate cancer, as is the case for each type of cancer. When discussing prostate cancer, it is important to consider the gland's anatomical location and its relationship to surrounding organs, such as the rectum, blood vessels, and muscles. The management of prostate cancer is quite complex. However, understanding every detail is not required at this stage. What is essential is a clear grasp of the key messages, along with a few specific details. ### Prostate Cancer #### Epidemiology Prostate cancer is the most common non-cutaneous cancer diagnosed in males, particularly in Western countries. A comparison between incidence and mortality rates shows that the incidence of prostate cancer is far higher than its mortality rate. This discrepancy is due to several factors, including an understanding of the natural history of the disease and the treatment options available today. This diagram compares the impact of prostate cancer with other cancers. Around 300,000 men die from prostate cancer annually. Therefore, while it is not the deadliest form of cancer, it still presents a significant global health burden. When stratifying the incidence of prostate cancer geographically, certain regions, such as Asia, exhibit notably lower rates compared to others. This geographic variance raises questions about risk factors, particularly genetic predispositions. Other factors to consider include the quality of life, dietary habits, and environmental influences. Prostate cancer is highly heterogeneous, with an incidence ranging from 6.3 to more than 80 per 100,000 people. This wide range underscores the variability of the disease. Further analysis of incidence and mortality across different countries reveals a significant gap between the two rates. This difference is uncommon in oncology, where high incidence typically correlates with high mortality. It suggests that novel techniques and technologies may be playing a role in improving treatment outcomes for prostate cancer. There was a notable increase in prostate cancer incidence starting around 1990. This spike can be attributed to the discovery of prostate-specific antigen (PSA, covered in later part of lecture) in 1986. PSA is a biomarker for prostate neoplasms that allows for the early detection of cancer. The widespread use of PSA testing led to a temporary surge in diagnoses. However, after the initial spike, the incidence has not continued to rise significantly. The question arises as to why there was no sustained increase in diagnoses over subsequent years, which will be addressed in the next slides. #### Prostate Cancer In Italy In the specific context of Italy, the probability of surviving one year after a prostate cancer diagnosis is very high, at 97%. An interesting aspect of this is seen in the diagram, where it is shown that for a patient diagnosed with prostate cancer at the age of 58, considering a median life expectancy of 84 years, the cancer could reduce life expectancy by up to 7 years. On the other hand, for a patient diagnosed at 70 years old, the impact on life expectancy is negligible. This finding is quite significant when considering the different ages at diagnosis and the overall impact of prostate cancer on survival. It is also important to consider the treatment options for elderly patients. These factors must be kept in mind when discussing different types of therapy for prostate cancer. The Italian situation is notably heterogeneous, with life expectancy being significantly higher in the northern regions compared to the southern regions. This disparity is not due to ethnic differences but is likely related to access to adequate healthcare and disease management. #### Other Risk Factors For Prostate Cancer - Ethnicity - Age - Family History - Genes - Obesity Ethnic background also plays a role in prostate cancer incidence, with non-Hispanic black men showing the highest rates. Interestingly, when Asian descent migrate to Western countries (United States), and adopt western dietary habits, their risk of developing prostate cancer increases. This suggests that environmental factors, particularly diet, have a significant impact on cancer incidence, beyond genetic or ethnic predisposition. When evaluating the incidence rates across different age groups, there is a clear upward trend. Prostate cancer is primarily a disease of men aged 50 and older, with incidence peaking after age 70. The likelihood of developing prostate cancer in men is - younger than 40 or 50 is extremely low = Approximately 1 in 10,000. - Aged 40 to 60 = Approximately 1 in 100 - Aged 60 to 80 = Approximately 1 in 8 #### Histology Of Prostate Cancer Regarding histology, 95% of prostate cancers are adenocarcinomas. This is significant because, despite the high incidence of prostate cancer, the histological uniformity allows for a consistent understanding of the disease's natural progression. This uniformity is crucial, as it enables predictions about the evolution of the disease based on the stage at diagnosis. #### Prostate Cancer Classification The Gleason score is a grading system used to assess the aggressiveness of prostate cancer. It is based on two components: the primary Gleason pattern, which reflects the most common cell differentiation pattern in the tumor, and the secondary Gleason pattern, representing the second most common pattern. The pathologist assigns grades to these patterns, and the combination of the two gives the Gleason score, which helps determine the tumor's aggressiveness. More recently, the Gleason score has been replaced by the ISUP grading system, which categorizes prostate cancer into five distinct groups based on cellular differentiation. The level of differentiation is directly related to the cancer's aggressiveness and prognosis. For example, patients in ISUP grade 1 generally have a very favorable prognosis, while those in ISUP grade 5 are at high risk of developing metastases or experiencing rapid local progression. Identifying the grade of the tumor during a biopsy, such as a preoperative biopsy, is critical for estimating prognosis and selecting the most appropriate treatment for the patient. ### Prostate Cancer Symptoms In terms of symptoms, many older men (aged 60 to 70 years) often experience urinary symptoms related to benign prostatic hyperplasia rather than prostate cancer itself. These symptoms are not typically a direct result of the malignancy. It is extremely rare for prostate cancer to present with symptoms due to the infiltration of the bladder wall or the ureter. In most cases, prostate cancer is completely asymptomatic. Occasionally, there may be a single episode of hematuria (blood in the urine) or bone pain, but these symptoms typically occur only in advanced cases when the cancer has spread to the bones. The majority of prostate cancer patients, however, are asymptomatic. ### Diagnosis of Prostate Cancer Diagnosing prostate cancer relies heavily on collecting comprehensive medical history, especially data regarding family history. It is well known that the BRCA1 and BRCA2 genes are associated with a higher incidence of prostate cancer in males and breast cancer in females. Recognizing a genetic predisposition to prostate cancer is crucial because it allows for earlier initiation of screening programs. In cases of early diagnosis, radical treatments can be offered, as heritable forms of prostate cancer are often more aggressive and require early intervention. After gathering the patient's medical history, the next step in the diagnostic process is a physical examination, specifically a digital rectal examination (DRE). This involves the use of a finger to palpate the prostate gland. Although some may perceive this technique as outdated, it remains highly effective in assessing not only the size of the prostate but also the presence of induration or nodularity, which may indicate malignancy. While a DRE can be uncomfortable for the patient, it is essential to inform the patient that it is a fundamental step in evaluating prostate health and is critical for initial cancer detection. Following or concurrent with the DRE, the prostate-specific antigen (PSA) test is often performed to evaluate the risk of prostate cancer. #### PSA and Prostate Cancer Diagnosis PSA is a protease produced exclusively by the prostate, but it is important to emphasize that PSA is prostate-specific, not prostate cancer-specific. There are many conditions that can cause elevated PSA levels, including urinary tract infections, prostatitis, and even activities like recent prostate stimulation or bicycling, which can elevate PSA. Certain medications can also influence PSA levels. The typical PSA threshold is set at 4 ng/mL, but this value may be adjusted based on the patient's age. For instance, a PSA level of 3.5 ng/mL in a younger patient may be cause for concern, while a PSA level of 4.5 ng/mL in an older patient with an enlarged prostate may not be as alarming. Among 100 patients with elevated PSA levels, only about 3% of these patients will have a prostate cancer diagnosis. However, it is also important to note that approximately 2% of prostate cancer cases occur without an elevated PSA, underscoring the importance of considering multiple diagnostic tools beyond just PSA levels. #### Additional Tests For Prostate Cancer Ultrasonography is generally not useful for diagnosing prostate cancer because the ultrasonographic pattern of the cancer appears similar to that of the normal prostate gland. Therefore, specific nodules cannot be detected through ultrasonographic evaluation alone. The investigation with the highest sensitivity and specificity for prostate cancer is the multi-parametric magnetic resonance imaging (mpMRI). It is MRI with multiple imaging parameters to assess the specific characteristics of prostate tissue. For example, a neoplastic area of the prostate may show an increased uptake of contrast, and this enhancement could indicate a more aggressive cancer. In addition, evaluating the water concentration in certain areas can help detect neoplastic lesions. Based on these findings, different zones of the prostate can be evaluated for cancer risk. Nuclear medicine doctors classify the risk levels using the PI-RADS (Prostate Imaging Reporting and Data System) scoring system, which has five levels of suspicion. - PI-RADS 1 & 2 = Indicate zones that are likely normal and have no significant suspicion of an aggressive neoplasm. - PI-RADS 3 = Intermediate risk, where no definite lesion is observed, but some abnormalities suggest the potential for malignancy. - PI-RADS 4 & 5 = Associated with a high or very high suspicion of cancer. After performing a multi-parametric MRI, a detailed map of the prostate gland can be generated, identifying specific areas of suspicion. Biopsies can then be taken from these targeted zones to improve diagnostic accuracy. A transrectal ultrasound (TRUS) guide is often used to collect biopsy samples, and it is also possible to fuse the MRI images with live ultrasonographic images for enhanced precision in targeting suspicious areas during the biopsy. # Lezione 6 ## Prostate Cancer Part 2 ### Diagnosis Continuation: #### Biopsy A biopsy, utilizing the tru-cut technique, involves the insertion of small needles to collect not only cells but also a tissue fragment. This procedure is essential for accurately assigning the Gleason grade, as the pathologist must evaluate not only individual cells but also the architectural patterns to better assess the neoplasm's aggressiveness. #### Side Effects: - Hematuria or light hematuria - Fever - Urinary retention - Edema Particularly when the prostate is enlarged, the stimulation and edema caused by the biopsy may lead to a further increase in prostate volume, potentially exacerbating lower urinary tract symptoms (LUTS) and, in some cases, resulting in urinary retention. It has been demonstrated that it is essential not only to collect samples from suspected areas identified by multi-parametric magnetic resonance imaging (MRI) but also to perform a standard biopsy to create a comprehensive and detailed map of the prostate. This approach allows for improved management of the neoplasm by identifying its precise distribution. Additionally, there are instances where normal samples may be obtained from the suspected areas indicated by MRI, while a neoplasm might be present in other regions of the prostate that exhibit a normal pattern on MRI evaluation. ### Staging #### TNM Classification: The TNM classification describes both the local and distant status of a neoplasm: - **T** represents the local extension of the neoplasm, - **N** represent the involvement of the lymph nodes, - **M** represents the presence or not of distant metastases. - T1A and T1B: These subcategories belong to the incidental diagnosis of prostate cancer discovered during interventions for benign prostate enlargement. For instance, a transurethral resection of the prostate (*TURP*) may be performed on a patient with normal PSA levels who presents with lower urinary tract symptoms (LUTS) that cannot be managed with medication. During histopathological evaluation of the resected prostate tissue, the pathologist may identify the presence of cancer. The staging is then determined based on the percentage of cancer found in the resected tissue, with distinctions made for less than 5% (T1A) or more than 5% (T1B) involvement. This percentage significantly influences subsequent patient management and treatment decisions. - T1C: This third subcategory of T1, known as T1C, refers to prostate cancer that is detected exclusively through biopsy. This occurs in cases where an elevated PSA level is observed, but both the digital rectal examination and imaging results are normal, leading to the decision to perform a biopsy, which