​Kembara Xtra - Medicine - Prostate Cancer

​Kembara Xtra - Medicine - Prostate Cancer 
A male reproductive organ called the prostate contributes seminal fluid to the ejaculate.
In an adult guy, the prostate gland has a volume of 20 to 25 g and is roughly the size of a walnut. It tends to become larger around the age of 50.
The functional anatomy of the prostate is divided into three areas: the peripheral zone (largest), the central zone (which contains the ejaculatory ducts), and the transition zone (located in the middle, next to the urethra). The peripheral zone is where prostate cancer most frequently develops.
Prostate-specific antigen (PSA), which is produced by prostate epithelial cells and is employed in screening and as a tumor marker, is produced.

Prevention Incidence
In 2021, there will be an anticipated 248,530 new cases of prostate cancer (CaP) in men in the United States, accounting for 13.1% of all cancer diagnoses.
Prevalence
According to estimates, 34,130 men will pass away from CaP in the US in 2021, accounting for 5.6% of all cancer fatalities.
Age upon diagnosis was 67 years on average, and the risk of CaP was 10.9% (1 in 9) or older.
PCa is the second most prevalent cause of cancer-related death in males and the non-skin cancer that is most frequently diagnosed in men in the United States (12.1% lifetime risk).
In 50% of males in their eighth decade of life, latent CaP foci are discovered during autopsies.

Pathophysiology and Etiology 

 Most prevalent type of transitional cell carcinoma: adenocarcinoma: >95%; nonadenocarcinoma: 5%
Location of CaP: 5–10% in the center zone, 20% in the transitional zone, and 70% in the periphery.

Risk Elements 

Age >50, African American ancestry, and favorable family history

Basic Prevention 
Finasteride use connected with moderate risk reduction in CaP but associated with an elevated risk of high-grade disease. There are no FDA-approved medications or dietary changes to prevent CaP.

Alert 

Prostate cancer screening is debatable.
According to the U.S. Preventive Services Task Force (USPSTF), men between the ages of 55 and 69 should explore the potential advantages and disadvantages of screening with their doctor before deciding whether to undergo routine PSA-based prostate cancer screening. A minor possible advantage of screening is that it may help some men from dying from prostate cancer. But many men will potentially suffer screening's negative effects. The USPSTF advises avoiding PSA testing in men under the age of 70. For males aged 55 to 69, the American Urological Association (AUA) panel advises shared decision-making between the patient and the doctor about PSA screening. Men under the age of 40 or any guy with a life expectancy under ten years should not have their PSA tested. When giving informed permission, statistics demonstrates that, if you screen 1,000 men between the ages of 55 and 69:
- Of the 240 who receive a positive test, only 100 will actually have PCa; of those 100, 80 will consent to treatment.
- One less person will pass away due to treatment, but 50 people will suffer erectile dysfunction (ED); 15 people will have lifelong incontinence.


Diagnosis 

Ask about CaP family history, bladder outlet obstruction symptoms, and other voiding symptoms.


clinical assessment 

DRE can be used to check for prostatic tumors, hardness, or asymmetry. It can also be used to check the lymph nodes and lumbar spine for metastatic signs.

Multiple Diagnoses 

Atypical small acinar proliferation (ASAP), prostatitis, prostatic intraepithelial neoplasia (PIN), and benign prostatic hyperplasia

Initial tests (lab, imaging) Diagnostic tests
CaP is generally concerned when total PSA is 4 ng/mL (sensitivity 21%, specificity 91%).
- Infection, inflammation, normal growth, natural PSA swings, and variations with elevated PSA levels are examples of other benign illnesses that might raise PSA.
- Manipulating the rectum won't dramatically increase PSA.
- Inhibitors of 5-reductase reduce PSA by about 50%.
 Additional PSA measures for CaP diagnosis include:
- Total PSA velocity: >20% baseline or 0.75 ng/mL/year for higher values increases CaP risk.
- Age-/race-adjusted PSA and free PSA are useful for assessing risk. Low percent free PSA is linked to an increased risk of CaP in patients with PSA levels between 4 and 10 ng/mL.
- PSAD 0.15 linked to greater CaP prevalence
PSA, DRE findings, MRI, and general clinical suspicion of CaP are taken into account when deciding whether to do a prostate biopsy, along with comorbidities and life expectancy.
Prebiopsy MRI is used to identify worrisome prostate lesions that should be targeted for biopsy. Standard biopsy: systematic random cores from peripheral zone base, mid-gland, and apex, 8 to 12 cores.
- Grade groups 1 to 5 are replacing the traditional pathologic grading system known as the Gleason grade.
From 1 (most differentiated) through 5 (least differentiated), the Gleason grade classifies specimens.
The Gleason score is determined by identifying and reporting both primary and secondary patterns (e.g., 3 + 4 = 7).
The majority of cases of prostate cancer are rated from 6 to 10, with 10 being the most fatal.
Grade group 1 equals Gleason 6, Grade group 2 equals Gleason 3 + 4 equals 7, Grade group 3 equals Gleason 4 + 3 equals 7, Grade group 4 equals Gleason 8, and Grade group 5 equals Gleason 9 and 10
 Staging: TNM (tumor, node, and metastasis) staging is used to produce a clinical and pathologic stage that determines the course of treatment. Clinical staging looks like this:
T1: cancer discovered by chance during TURP or discovered during biopsy for increased PSA; T2: cancer discovered during DRE but limited to the prostate; T3: cancer discovered to have expanded locally outside of the prostate and/or the seminal vesicle; T4: cancer invading surrounding organs; N1: local lymph node spread
M1: remote metastases
Tests in the Future & Special Considerations
For high-risk tumors, a bone scan, MRI, CT, or PET scan may be recommended.

Management 
Use the Prostate Predict Calculator at https://prostate.predict.nhs.uk to assist patients in weighing their treatment options.
● Options for treatment include:
- Watchful waiting: observation with the goal of alleviating symptoms
According to the ProtecT trial from 2016, careful waiting was just as deadly for all causes and people with cancer as surgery or radiotherapy. Although there was reduced disease progression (including metastatic disease) in the treatment arms, there was also a significant increase in morbidity (ED and ED-related urine and bowel problems).
- Active surveillance: regular repeat biopsies and continuous monitoring of PSA and DRE
- Pelvic lymph node dissection (PLND) during radical prostatectomy
- External beam radiation treatment (EBRT)
- Brachytherapy: radioactive implants put in the prostate as a possible treatment for early-stage localized prostate cancer
- The use of antiandrogens
(Surgical castration) Bilateral orchiectomy
 Medical castration with a gonadotropin-releasing hormone (GnRH) agonist, antagonist, or antiandrogen
17-hydroxylase inhibitor abiraterone (CYP17A adrenal androgen production)
 Androgen receptor antagonists bicalutamide, nilutamide, flutamide, enzalutamide, and apalotamide
- Multiple chemotherapeutic drugs are utilized in chemotherapy to treat castrate-resistant prostate cancer (CRPC).
- Risk elements
 The probability of recurrence following definitive treatment is taken into account when categorizing treatment choices, including very low-risk, low-risk, favorable intermediate-risk, unfavorable intermediate-risk, high-risk, and very high-risk categories.
 To be low risk, a patient must satisfy all three requirements; failing to do so places them in the higher risk category. Clinical stage, serum PSA (ng/mL), and grade group for the risk category: Low T1-T2a/10/1, Intermediate T2b-T2c/10/1–20/2–3, and High T3a/>20/4-5
The distinction between favorable and unfavorable intermediate risk is based on additional clinical/pathologic criteria, as are the very low and very high risk groups.
The extremely low risk, favorable and unfavorable intermediate risk, and very high risk groupings are now included in updated risk classification algorithms.
 Regional CaP
Very low and low risk: Active surveillance is the mainstay of treatment; radical prostatectomy and radiation therapy are possible options.
Radiation therapy or radical prostatectomy are the mainstays of treatment for intermediate risk prostate cancer, and active surveillance may be made available to patients who fall into the favorable intermediate risk category.
High and extremely high risk: Radical prostatectomy or radiation therapy are the mainstays of treatment; adjuvant radiation may be considered depending on the pathologic results of the prostatectomy.

Alert 

Determining life expectancy and informing the patient of the advantages and disadvantages of surveillance and treatment choices are essential.
Androgen deprivation therapy (ADT) and radiation are the mainstays of treatment for locally advanced CaP; surgery and adjuvant radiation are also employed.
- It has been demonstrated that adding abiraterone + prednisone to long-term ADT for high risk (T3-T4, Gleason 8 to 10, PSA >40), locally advanced prostate cancer considerably improves overall survival.
Metastatic CaP: RT and ADT are the cornerstones of treatment.
ADT with abiraterone + prednisone for lower volume disease; early chemotherapy (docetaxel) with ADT for high-volume disease
- ADT details:
Leuprolide, goserelin, histrelin, or triptorelin are examples of GnRH agonists.
Degarelix is a GnRH antagonist that inhibits testosterone synthesis and prevents the flare phenomenon that is associated with GnRH agonists.
Osteoporosis, gynecomastia, ED, decreased libido, obesity, lipid abnormalities, diabetes, and cardiovascular disease are side effects of ADT.
 The flare phenomenon, or illness flare (hot flashes, lethargy), might happen after starting GnRH agonist medication because of a brief rise in testosterone levels.
If spinal cord metastases are present, it is possible to reduce the risk of cord compression during a testosterone flare by beginning antiandrogen therapy before beginning a GnRH agonist.
 GnRH agonist and antiandrogen combined with androgen blocking (e.g., bicalutamide, nilutamide, or flutamide) may be used to stop flare-ups.
CRPC - CRPC is characterized as disease progression after ADT.
The following are included in treatment:
Not metastatic
Add antiandrogen (apalutamide, darolutamide, or enzalutamide) and continue ADT.
Tumor and germline testing are advised for metastatic cases. first-line therapy
Abiraterone: used in conjunction with prednisone as a CYP17A (adrenal androgen production) inhibitor
Enzalutamide, an androgen receptor antagonist, and docetaxel, a chemotherapy drug that prevents microtubule formation
Radium-223 (radiopharmaceutical) for individuals with symptomatic bone metastases and Sipuleucel-T, an immunotherapy
 Mitoxantrone for patients with visceral metastases who are symptomatic and resistant to conventional treatments

Second line (if abiraterone/enzalutamide is used as the first line therapy): Docetaxel or sipuleucel-T is preferable.
 Ruparib, radium-223, pembrolizumab, or olaparib in certain patient populations
Additionally suggested were abiraterone, cabazitaxel, enzalutamide, and fineparticle abiraterone.
Second-line drugs should be abiraterone, cabazitaxel, or enzalutamide if docetaxel was used in the first instance.
 In certain patient populations, mitoxantrone, olaparib, pembrolizumab, radium-223, or rucaparib
Additionally suggested were fine-particle abiraterone, sipuleucel-T, and docetaxel challenge.
177Lu-PSMA-617 received FDA Breakthrough Therapy designation and could be a new therapy option for CRPC patients who have developed metastatic disease.
Bone health - Pathologic fractures are more likely to occur in men with prostate cancer, especially those receiving ADT.
 Provide vitamin D and bone density supplements.
Denosumab, a RANK-ligand inhibitor that stops osteoclast activity, and zoledronic acid, a bisphosphonate, can both be prescribed as preventative measures.

Take Action 
Prostatectomy: periodic PSA and DRE testing. CT, MRI, PET, and bone scans were acquired at the recurrence. Salvage radiotherapy +/ ADT is taken into consideration if the PSA recurrence is caused by local illness. Androgen restriction is used for metastatic illness.
XRT: PSA and DRE are advised on a regular basis.
A combination of a CT, MRI, PET, and bone scan is typically done. Biochemical recurrence is defined as a PSA increase of 2 ng/mL above nadir. Salvage prostatectomy, cryosurgery, brachytherapy, or high-intensity focused ultrasound (HIFU) are options if the PSA recurrence is believed to be caused by local disease. Androgen deprivation is taken into consideration for metastatic illness.


The prognosis for advanced disease is excellent if the lesions are hormone responsive. Localized disease is typically treatable.
 Local 100%, regional 100%, and distant 30.2% for 5-year CaP survival, respectively.
If there is extraprostatic extension, seminal vesicle invasion, or positive surgical margins, the risk of recurrence is higher.

Complications 

Urinary incontinence and erectile dysfunction are the most frequent post-prostatectomy complications.
Urinary incontinence, ED, radiation cystitis, and radiation proctitis can all be treated with radiation therapy. For ED, PDE5 inhibitors, intracavernosal injections, intraurethral suppositories, vacuum pumps, and penile prostheses are among the available treatments.
 Oral medicines, urethral slings, and prosthetic sphincters are available treatments for incontinence.

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