JHU - Understanding Prostate Cancer

Last updated Mar 6, 2023

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• Source:: Understanding Prostate Cancer | Coursera
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About this Course
Welcome to Understanding Prostate Cancer. My name is Ken Pienta, Professor of Urology and Oncology at the Johns Hopkins School of Medicine. I have been studying prostate cancer and treating patients with prostate cancer for over 25 years.
Over 1,000,000 men worldwide and 230,000 men in the United States are diagnosed with prostate cancer every year. Three hundred thousand men worldwide and 30,000 men in the US are dying from prostate cancer every year. As people live longer, the incidence of prostate cancer is rising worldwide and prostate cancer continues to be a major health problem. Thanks to years of dedication and commitment to research we’ve made enormous advances in the treatment of prostate cancer, But there is still a lot of work to be done. In this Understanding Prostate Cancer course, I will provide an introduction to the biology of prostate cancer as well as how it is identified and treated at various stages of the disease.

• The prostate is one of the male sex organs
  • It produces prostate specific antigen (PSA), an enzyme that helps liquefy the ejaculate
  • It is not necessary for erections or for reproduction
• Benign Prostatic Hyperplasia (BPH)
  • With age, the prostate often gets larger
    • This is termed benign prostatic hyperplasia
    • It’s also termed benign prostatic hypertrophy.
  • This benign enlargement of the prostate can make it difficult to urinate.
    • It is treated with medicines or surgery,
  • BPH is not cancer
  • It is not related to the risk of developing cancer.
• Prostate Cancer is an Adenocarcinoma.
• Prostate Cancer develops over time and is associated with precursor lesions
• The Western diet may influence risk of developing cancer.
• Asian men, when move to the west, increase their risk of cancer.
• Screening
  • Digital Rectal Exam
    • Yearly digital rectal exam starting at age 50
    • A health care provider places a finger in the rectum to feel for a lump in the prostate that would indicate the possibility that a cancer is growing
  • Prostate Specific Antigen (PSA)
    • PSA test should be discussed with a health care provider as a yearly test between the ages of 55-69
    • PSA is a protein produced by cells of the prostate gland
    • The PSA test measures the level of PSA in a man’s blood
    • For this test, a blood sample is sent to laboratory for analysis
    • The results are usually reported as nanograms of PSA per milliliter (ng/mL) of blood
    • A normal PSA level is considered to be 4.0 ng/mL or less

• If the PSA is elevated, or the digital rectal exam is abnormal, the next step is a prostate ultrasound and biopsy.
• Prostate Cancer Ultrasound and Biopsy
  • An ultrasound probe is placed in the rectum
  • Ultrasound uses sound waves to image the prostate
  • For the biopsy, typically a urologist will perform 12 biopsies to sample the various areas of the prostate.
  • It is all done at the same time that the ultrasound tool is in the rectum.
  • If a lesion is seen on ultrasound, two biopsies are performed in that area, and that is sometimes referred to as a 12-plus-2 biopsy.
  • In general, the doctors or urologists divide the prostate into three zones, the peripheral zone, the central zone, and transition zones. Most prostate cancers arise in the peripheral zone, the outer area of the prostate, which is next to the rectum.
• If a doctor is worried that the cancer has invaded locally beyond the prostate, an MRI of the prostate can be performed.
  • This used to require putting a probe into the rectum, but now, that is no longer necessary.
  • Magnetic resonance imaging, or MRI, of the body uses a powerful magnetic field that produces pictures of the inside of the body without the necessity of a recto-probe.
  • The MRI produces a very clear picture of the prostate, and can demonstrate and tell us if the prostate cancer has broken through the prostate into the surrounding structures.
• If the doctor is worried that cancer has spread to the lymph nodes, a CAT scan of the abdomen-pelvis is performed.
  • A computerized tomography, or CT scan, combines a series of X-ray images taken from different angles, and uses computer processing to create cross-sectional images or slices of the bones, blood vessels, and soft tissues inside your body.
  • A CT scan can find enlarged lymph nodes, for example, shown at the arrow. But does not tell us if the enlarged lymph node is from cancer or some other process, like inflammation or infection.
• If a doctor is worried that cancer has spread to the bones:
  • Bone Scan
    • A bone scan is a nuclear imaging test that helps diagnose and track several types of bone disease.
    • A bone scan uses technetium-99, a radionuclide that goes to where bone is being damaged, regardless of the cause.
    • Damage to the bones shows up as dark areas on the skin.
    • A bone scan is not cancer-specific, but can suggest to doctors that prostate cancer has spread to the bone.
  • X-rays
    • X-rays can be done to further access bone damage.
    • The X-ray is not cancer-specific, but can suggest to doctors that prostate cancer has spread to the bone.
• TNM System
  • The T stage for prostate cancer is special, because of the T1c designation.
    • T1c refers to a small prostate cancer that is detected by PSA screening. It cannot be felt by a digital rectal exam.
    • A T2 cancer can be felt by digital rectal exam, and it is confined to the prostate.
    • A T3 cancer is invading through capsule.
    • A T4 cancer is when that invading tumor is invading into the rectum, or bladder specifically.
  • Node Status, cancer staging is first done based on clinical and imaging assessments.
    • If a CT scan is not performed, we don’t know the node status and the clinical stage is the Nx.
    • If a CT scan is performed, and no lymph nodes are seen, the patient stage is clinical stage N0 or no regional lymph nodes.
    • If regional lymph nodes are seen on the CT scan, the patient is staged at clinical stage N1.
  • The M for metastases staging, again, tells us whether cancer is detected on clinical imaging.
    • Mx means it was not assessed, for example, a bone scan was not done.
    • M1 says that we have found metastases, or evidence that suggests metastases somewhere.
    • M1a refers to lymph nodes that are beyond the pelvis.
    • M1b is disease in the bones
    • M1c is disease in other sites, for example, the liver or lungs.
• Prostatic Intraepithelial Neoplasia (PIN)
  • It is considered a precursor lesion to cancer.
  • In this case, the glands start to involute a little bit, and there is associated inflammation in the stroma next to it.
• Histology Grading: Based on Gleason Scoring
  • 
  • Dr. Gleason was a famous pathologist who developed a scoring system for changes in the prostate, as it became more and more undifferentiated.
  • He designed the system that scored what he was looking at under the microscope from 1 to 5.
  • Pattern one was small, uniform glands that were well differentiated.
  • Pattern two was more stroma between these small glands, with the appearance of more disorganization.
  • Pattern three demonstrated that these glands were starting to break down, and have infiltration into the stroma.
  • Pattern four demonstrated irregular masses of these glands, so that you started to lose the glandular formation.
  • And Pattern five was simply sheets of anaplastic cells with very few glands at all.
• The Gleason Score
  • Primary grade – assigned to the dominant pattern of the tumor (has to be greater than 50% of the total pattern seen)
  • Secondary grade – assigned to the next-most frequent pattern (has to be less than 50%, but at least 5%, of the pattern of the total cancer observed)
  • Tertiary grade – increasingly, pathologists provide details of the “tertiary” component. This is where there is a small component of a third (generally more aggressive) pattern.
• The Gleason’s score is associated with risk of recurrence for patients, and is an important part of prostate cancer staging and grading.
• Overall, staging for prostate cancer requires thinking about the TNM system, tumor nodes metastasis system, as well as the grade. Once you have the TNM system and the grade, you can assign a stage, stage 1, stage 2, stage 3 or stage 4.
• The Partin Tables
  • The Partin Tables use clinical features of prostate cancer – Gleason score, serum PSA and clinical stage – to predict whether the tumor will be confined to the prostate.
  • The tables are based on the accumulated experience of urologist’s performing radical prostatectomy at the James Buchanan Brady Urological Institute at Johns Hopkins.
  • For decades, urologists around the world have relied on the tables for counseling patients preoperatively and for surgical planning.
• Main Treatment Types
  • Surgery and Radiation
    • Approximately 50% of all people diagnosed with cancer in the United States are cured by surgery or radiation, because the cancer is removed or killed by radiation before it has spread.
    • Surgery and radiation provide the backbone for all cancer therapy.
      • Surgery removes the tumor.
      • Radiation can be given as external beam radiation or by implanting radioactive seeds into the tumor to kill the cancer cells.
    • The main surgical treatment for prostate cancer is Radical Retropubic Prostatectomy
      • A prostatectomy is a surgical procedure for the removal of the prostate.
      • It’s performed to treat prostate cancer.
      • The prostate, seminal vesicles, and lymph node near the prostate are removed. The term radical is used with surgery when the whole organ is removed.
      • In the open approach, the surgeon takes the prostate out through an incision in the abdomen between the umbilicus, or belly button, and the pubic bone.
      • In a laparoscopic approach, the surgeon makes several small cuts and long, thin tools are placed inside the cuts. The surgeon puts a thin tube with a video camera (laparoscope) inside one of the cuts and instruments through the others. This helps the surgeon see inside during the procedure.
        • Sometimes, laparoscopic surgery is done using a robotic system.
          • The surgeon moves the robotic arm while sitting at a computer monitor near the operating table.
          • This procedure requires special equipment and training.
          • Not every hospital can do robotic surgery, however it should be noted that in the United State most prostatectomies that are done laparoscopicly are done with the help of a robot.
      • Most radical prostatectomies are done with nerve sparing in mind.
        • Nerve sparing can be done with either the the open or laparoscopic approach.
        • The nerves run in bundles along both sides of the prostate.
        • Sometimes nerves must be cut in order to remove the cancerous tissue.
          • For example, if the cancer invades the nerves or grows too close to the nerves, the surgeon will not risk not getting all the cancer out, and takes the nerve with the cancer.
          • If both sides of the nerves are cut or removed, the man will be unable to have an erection. This will not improve over time.
            • There are interventions that may help restore erectile function, and we will discuss those in lecture five.
          • If only one side of the bundles of nerves is cut or removed, the man may have less erectile function, but will possibly have some function left.
          • If neither nerve bundle is disturbed during surgery, function may remain normal.
          • However, it sometimes takes months after surgery to know whether a full recovery will occur.
            • This is because the nerves are handled during surgery and may not function properly for a while after the procedure.
    • External beam radiation therapy, or ERBT, is given in several doses or fractions over time.
      • A total dose of 75-80 gray, which is a measure of radiation, is given over approximately 7 weeks.
      • This radiation is given through conformal planning, the treatment is guided by CT scans. Shorter schedules with higher dose fractions are being tested, but the majority of men in the United States are still treated over 7 weeks of time with 75-80 gray.
      • Intensity modulated radiation therapy, or IMRT, is an advanced mode of high-precision radiotherapy that uses computer-controlled linear accelerators to deliver precise radiation doses to the cancer or specific areas within the tumor itself.
      • IMRT is now the most common type of external beam radiation therapy given for prostate cancer.
        • The computer-driven machine moves around the patient as it delivers the radiation.
        • Along with shaping the beams and aiming them at the prostate from several different angles, the intensity, or strength of the beams, can be adjusted to limit the doses reaching nearby normal tissue, as the machine moves around the patient.
      • Some newer radiation machines have imaging scanners built right into them.
        • This advance, known as image guided radiation therapy, or IGRT, let’s the doctor take pictures of the prostate and make minor adjustments in aiming just before giving the radiation.
      • Another variation of IMRT is called volumetric modulated arc therapy, or VMAT.
        • It uses a machine that delivers radiation quickly as it rotates once around the body.
        • This allows each treatment to be given over just a few minutes.
        • Although this can be more convenient for the patient, It hasn’t yet been shown to be more effective than regular IMRT.
    • Brachytherapy, also called seed implantation or interstitial radiation therapy, uses small radioactive pellets, or seeds, each about the size of a grain of rice that are placed directly into the prostate.
      • This is generally used only in men with early-stage, low-grade disease.
      • Brachytherapy combined with EBRT is sometimes an option for men who have a higher risk of the cancer growing outside the prostate.
      • There are two types of brachytherapy.
        • Permanent, or low dose rate, or LDR bracytherapy is performed when approximately 100 pellets, or seeds, of radioactive material, such as iodine-125 or palladium-103, are placed into the prostate and left in place.
        • Temporary brachytherapy, or high-dose rate, or HDR brachytherapy is done for a short time.
          • Radioactive iridium-192 or cesium-137 are placed via implants for 5 to 15 minutes and then removed.
          • Generally, about 3 treatments are given over 2 days.
  • Hormonal therapy
  • Chemotherapy: which is not generally used in local treatment
  • Targeted therapy: not generally used in local treatment
  • Immunotherapy: not generally used in local treatment
• How prostate cancer’s treated is guided by risk categories.
  • Risk actually refers to risk of recurrence.
  • Risk of recurrence refers to what the chance is that the cancer will recur or come back after treatment.
  • Men are offered treatment guided by the risk of recurrence.
  • Risk categories have been developed by monitoring thousands of men after treatment over many years.
  • They are based on initial PSA, cancer stage, PSA density, and Gleason score prior to treatment. PSA density is equal to your PSA divided by the prostate volume on ultrasound.
  • The risk categories have been summarized and treatment have been summarized by a panel of experts and published through the National Comprehensive Cancer Network (NCCN).
  • They are updated regularly, usually yearly.
  • The general categories of risk are very low risk, low risk, intermediate risk and high risk.

• It is an unfortunate fact that nearly a 100% of men with prostate cancer have involvement of their bones at the time of their death.
• The main treatment types for advanced and metastatic prostate cancer are
  • Hormonal therapy
    • The first line therapy for treating Metastatic Prostate Cancer is hormonal therapy to decrease circulating testosterone. This castrates the patient.
    • Eventually, hormone therapy almost always fails.
  • Chemotherapy
  • Targeted therapy
  • Immunotherapy
  • Systemic radiotherapy
  • Stereotactic body radiation therapy (SBRT)