Prostate Cancer: Screening, Diagnosis, and Management

• Prostate cancer is common and should be understood

Prostate Cancer Epidemiology

• Prostate cancer is the second most common type of cancer in males
• Itis the most common malignancy affecting males
• Incidence calculation involves the number of affected people within a year (around 29%)
• Prevalence calculation determines the number of existing cases with consideration that it may be higher if the disease is incurable or has a low mortality rate
• Prostate cancer’s prevalence is low because it can often be cured
• The cancer is the most common solid neoplasm in Europe, the USA, and the Western world
• Prostate cancer is not the top ontological concern in Asia
• Worldwide, prostate cancer is the second most diagnosed cancer among males
• Increased diagnoses of prostate cancer are linked to raised use of TURP and tests to detect prostate-specific antigen (PSA)
• PSA is a prostate-specific protein
• PSA testing is not done on every patient due to potential overdiagnosis
• Prostate cancer usually has a low mortality rate and is indolent, so it commonly doesn't affect life expectancy
• Mortality burden is still high, but mortality rate is lower.
• Survival rate is high, at 89% from 5-10 years, and if localized, mortality is nearly 0
• Mortality previously increased due to including patients who died from other causes but tested positive for prostate cancer
• Improvements in surgical and chemotherapy have decreased mortality in recent decades

Prostate Cancer Risk Factors

• Key prostate cancer risk factors include age, family history, and ethnicity
• Risk increases for those over 60, check around 50 is still needed
• Risk of cancer doubles with one first-line relative and increases 5-11 fold with two or more
• African descendants, specifically those in the US, are more likely to have it
• Mutations in BRCA and ATM genes are associated with higher chances of contracting the disease and aggressive tumors
• Genetic mutations are important for diagnosis and treatment
• Diet and lifestyle may not be risk factors due to lack of confirming data

Prostate Cancer Take Home Points

• Incidence is high and includes incident tumors in males in Europe and the US
• The mortality rate is low, but the mortality burden is high due to numerous cases
• Risk factors include age, ethnicity, and family history

PSA (Prostate Specific Antigen)

• PSA is a protein antigen for the prostate and a tumor marker
• It is part of the kallikrein-related peptidase family and comes from epithelial cells of the gland
• PSA liquefies semen and helps sperm to swim freely
• PSA is organ-specific but is not disease or tumor-specific
• PSA levels need to be related to the prostate's size and not tumor size
• It increases due to trauma, prostatitis, or inflammation, making PSA specificity not high
• The normal threshold for PSA is 4 ng/mL
• High-grade differentiated tumors are a rare type of tumor sometimes associated with a low PSA
• Diagnosis enhanced via markers like Free and Total PSA tested by PSA Ratio
• Total PSA levels between 4 and 10 ng/ml may require further free PSA testing
• The PSA ratio test: If the PSA ratio is around 30%, it likely indicates a benign condition, such as inflammation or enlargement
• PSA value of less than 10% might point to a tumor
• A value between 10 and 20% indicates that the test is not conclusive
• PSA density is calculated via the ratio between total PSA and the gland’s volume and helps when MRI results have low conclusivity
• FDA approves two additional tests not commonly used in Europe
• ERSPC Study: PSA screening is important and decrease mortality
• Standard tests show additional tumor diagnoses without increases to overall survival, so regular PSA-testing isn't implemented in healthcare systems
• Randomized PSA screening leads to increased diagnoses, though studies vary and the value of this method is controversial
• ERSPC shows that screening can diagnose PCa (IR: 1.23; 95% CI: 1.03-1.48) and more localized disease (RR: 1.39, [1.09–1.79])
• Screening shows a tendency to detect less advanced PCa, T3–4, N1, M1; RR: 0.85 [0.72–0.99]
• Trials mainly found no PCa-specific survival benefit (IR: 0.96 [0.85–1.08]) or overall survival benefits (IR: 0.99, 95% CI: 0.98–1.01)
• Prostate cancer screening remains controversial

Early Detection and Screening for Prostate Cancer

• Patients should be counselled about the negatives and positives of all specific antigen (PSA) testing
• Adopt tailored, risk-based detection for well-aware men with at least 15 years of life expectancy
• Test those with elevated PCa risk early (men from 50, 45 with PCa family history, African descent from 45, or BRCA2 mutation carriers from 40)
• Risk-based approach suggested for initial PSA levels, checking at 2-year intervals for those at risk
• With PSA under 1 ng/mL test for those at 40, with PSA under 2 ng/mL test for those at 60
• If the patient is low risk, postpone testing for up to eight years
• End the early PCa testing if life expectancy and performance are low and if the patient has less than 15 years to live
• PSA tests begin at 50 with no prior risks, but excessive PSA testing should be avoided
• PSA testing should begin at age 45 with BRCA mutations if there is a family history of PCa
• Testing should start at 40 years of age if there are familiarity or ethnicity-related risks
• Repeat tests after up to 8 years if the levels remain normal
• Asymptomatic patients with a less than 10-year life expectancy are often screened and the indolent cancers should be ignored

Prostate Cancer Diagnosis and Staging

• Localized prostate cancer is more common and asymptomatic

• Metastatic prostate cancer is less common and more likely to have symptoms

• Diagnosis relies on histopathologic verification of adenocarcinoma through biopsy or operative samples

• Symptoms are rare, but if there are symptoms:

• Local or bone pain

• Bleeding

• Hematuria

• Kidney injury

• Erectile dysfunction

• Lower limbs edema

• Obstruction, or lower unitary tract symptoms (LUTS) for example, due to gland enlargement, though this zone usually won't give obstructive symptoms unless the tumor grows to an advanced stage

• Benign hyperplasia leads to obstructive symptoms in the inner urethra

• Symptoms usually appear in advanced or metastatic cancer, but most patients are asymptomatic with positive PSA screenings

• Probable metastasis may be present with back pain and PSA of 100

Digital Rectal Examination (DRE)

• Digital rectal examination is the prime, major marker in urology that is simple and inexpensive
• DRE is low and limited in terms of sensitivity and specificity
• specificity refers to the number of patient's with a negative digital rectal examination that are not actually affected by the disease
• sensitivity refers to the true positives of the test
• DRE evaluates the gland's posterior peripheral area and doesn't sense the transition zone or central zone
• DRE shouldn't be painful and can identify if the tumor is extra capsular
• Can identify size, consistency and uniformity as well as nodules
• Suspected PCa may be detected by DRE alone 18% of the time, regardless of the PSA level
• DRE often misses extracapsular tumor extension and confined tumors
• Experts confirm extracapsular extension with fingers

Prostate Cancer Imaging Techniques

• Traditional transrectal US (TRUS) is inaccurate, low resolution, and can't diagnose PCa
• TRUS is used for US guided biopsy to find prostate margins
• Endocavitary magnetic resonance imaging (MRI) is more accurate and has been implemented in recent years
• MRI is best done previous to biopsy because it allows better imaging of tumors, determining the percentage of tumor present
• Functions include T2-weighted to detect tumors as hypointense areas, diffusion-weighted to measure water movement, and dynamic contrast-enhanced imaging to measure neoplastic genesis
• Compare imaging to PI-rad systems (prostate imaging-reporting and data system)
• Randomly sampling areas allows for tumor discovery with MRI visibility
• In biopsy-naive patients, systematic biopsy occurs; perform targeted biopsy still if previous cases are suspected
• Micro-ultrasound with higher resolution provides higher quality images over traditional ultrasound
• PRI-MUS scores correlate with cancer risk

All Patients Recommendations

Use MRI as the initial screening and follow the PI-RADS standards and MDT feedback

Biopsy-Naive Patients Recommendation

• MRI perform before prostate biopsy needed
• If MRI is positive, combine targeted and systematic biopsy, if negative, omit a biopsy
• Positive MRI signals combined targeted plus systemic biopsy.
• Negative MRI suggests low clinical PCa risk, omitting a biopsy
• Previous negative biopsies can still take MRI and a biopsy through clinical suspicion, though MRI is still needed

PSA Density Testing

• Key indicator for PI-RADS when the tumor's presence is doubted
• If its value is high on the prostate, then it's likely a tumor is probably
• A prostate-specific antigen density cutoff is 0.15 ng/ml/cc is a commonly recommended threshold
• Depending on the results, a biopsy can be taken into consideration

Summary

-PSA tests can be influenced by factors like infection and are recommended to be tested last

Transrectal vs Transperineal Biopsy

1. Transrectal biopsy is most common as the needle is going through the rectum, which raises the likelihood of infections
2. Use the needle that passes perineum through the skin because it's cleaner than the transrectal biopsy

Pathology

• Adenocarcinoma is the most prevalent accounting for 95% of all cases
• Mesenchymal tumours accounts for 0.1-0. 2%
• Urothelial carcinomas make up 5%
• Gleason scores are scored with 2 numbers indicating the spread of tumors
• If it's higher-grade, that indicates a higher risk for malignancy

Grading

• ISUP grading (from 1 to 5) is a strong predictor of aggressiveness
• There are ISUP conversions based on Gleason scores
• The recurrent survival and cancer-specific deaths' is tied to its correlation
• The ISUP will differ overall based on Gleason scores

PCa Pathway

1. Start the test to get a family history and physical
2. Do an MRI and ultrasound to see if a medical exam is needed to stratify the patient due to certain risks for prostate cancer
3. Biopsy is the confirmation after seeing visible evidence from the imaging
4. End it all with an examination of the tumor

Tumor Staging

• T1 is nonpalpable but may be found with needle biopsy at random, or by tumor found by the patient T1
• T2 is palpable with the prostate
• T3 can palpitate and goes through the capsule that's attached to seminal vesicles
• T4 is fixed into adjacent structures and attaches to the external spinchter

N-staging

• N is staging lymphnodes through PN and CN pathologicals
• Use a tumor with clinical
• MRI and PET combined, the PSMA is another way to image tumors combined to make diagnoses more accurate

M-staging

• M-0 is no metastasis
• M1 has distant metastasis through the bones

PET/CT Scans

• Standard test for bone scans and combines more results from PSMA to enhance clarity
• They combine TNM into each case, the main method is to focus on grade, which can have multiple risks
• It's key that you can have low risk so as to eliminate tests from staging
• Tests for determining risk and that is key to determining diagnosis
• PSMA can be used with multiple tests

Treatment

• Use imaging and radiation for the staging information and the treatment to base the approach on for changing PSMA
• Is a treatment in terms of risk
• PSA is lower with ISUP grades so always use digital rectum readings
• GS > when PSA is high and GS high will only use GS for the patient with no ISUP
• 2 types or tumors to treat: localized and metastatic
• A patient whose life expectancy is not longer than 10 should be treated in systematic therapy
• If a patient is older than 80 and has no symptoms, they will not be treated

Treatment Options for PCa

• Active surveillance
• Ext beam radiotherapy and focal therapy
• Surgery or treatment with chemotherapy
• The best options are the first three while last is more investigational If a patient has a life expectancy of longer than 10 years, active surveillance is required
• It will reduce the localized cancer cases and it has excellent success
• The checkup requires annual biopsies and exams that make tests more sensitive than prior
• Watchful waiting is for those who have a shorter life

Localized cancer treatment

• Chemotherapy and focal therapy
• Tumor could quickly spread and it is important to keep that in check with regular check ups

Radical Prostatectomy

• Includes surgery, incisions, and robotics
• A skilled touch is need with many options
• A lymphadenectomy should be done
• External internal nodes are removed as well as nodes to the nerve
• The success of a prosectomy relies on the surgeon

Prostatectomy Outcomes

• Robot assisted surgeries result in less loss of blood loss
• The goal is to continue to preserve the sphinchter
• All parts must be connected in full between bladder and urethra

Treatment Completion

• Tests and images for tumors will result in the patient requiring further medical treatment based on the tumor
• Brachytherapy is needed when the doctor permanently implants small radioactive seeds inside the prostate

Surgery for Cancer

• Brachytherapy uses radiation with side effects and can also be combined with EBRT to treat the tumor
• Surgery and medication will determine focal therapy, while tumors will need either surgery or radiotherapy based on the intermediate
• Longterm goals prove to have successful FT with PCa care
• Remove the prostate and help with cancer growth
• Treatment of primary tumors will relieve patient symptoms which are reduced androgen hormones
• There's been a shift to reducing testicles due to pharmacological implications
• The goal is to chemically make you castrated, meaning the drug should stop from growth
• Therapy can be done if there's a metastasis, but is always targeted towards the cancer

Hormonal Options

• Agents increase treatment
• Drugs and systemic care will help to reduce stress from advanced diseases
• Testosterone will lead to cancer in the prostate
• Lesions are often questioned unless combined with other medical issues

Explore prostate cancer screening guidelines, diagnostic methods like histopathologic verification, and the clinical significance of findings. Understand the implications of PSA testing, digital rectal exams, and the importance of early detection for improved outcomes. Learn about risk factors and screening recommendations.