The Prostate Gland, Prostate Cancer, & Brachytherapy

1. The Prostate Gland, Prostate Cancer, & Brachytherapy Education Tool by Ivan Dublin,Nursing Student of Ryerson University In collaboration with the Prostate Centre at the Princess Margaret Hospital

2. The Prostate Gland

3. What is the prostate gland? • The prostate gland is a walnut-sized organ located just below the bladder and is comprised of two regions enclosed by an outer layer of tissue. It is one of the main components of the male reproductive system and plays a vital role in the development of the male sex organs.

4. What is the main function of the prostate gland? • The prostate gland’s main function is to add important fluids to the semen to help sustain the sperm during ejaculation. This protects the semen against naturally occurring acids located within the vagina.

5. Where is the prostate gland located? • The prostate gland is located just below the bottom of the bladder and above the rectum. As the diagram indicates, the prostate gland encircles the urethra at the point where the urethra connects to the bladder.

6. Important things to know about prostate growth • The prostate goes through two periods of growth throughout a man’s life. The first occurs during the beginning stages of puberty when it doubles in size. Its growth then stops until about age 25. At this time, it slowly begins to grow again and for some men can become problematic once they reach their early 50s. It is strongly recommended that all men over the age of 40 go for regular prostate exams and have a test called a Prostate Specific Antigen (PSA) test.

7. What is PSA? • PSA or prostate specific antigen is an enzyme produced by the prostate cells. PSA levels can be used as an indicator of prostate-related diseases, especially prostate cancer. As part of a general prostate health program, your doctor may recommend that you have a PSA blood test perform periodically.

8. Using PSA to evaluate prostate health • Elevated PSA is often associated with prostate cancer, however there are other conditions that cause an increased PSA. Benign prostatic hyperplasia (BPH or enlarged prostate), prostate cancer, and prostatitis are the most common reasons for an elevated PSA. • While an elevated PSA does not always indicate prostate cancer, ruling out prostate cancer should continue to be the first priority. A PSA score of greater than 4.0 is generally referred to follow-up to rule out prostate cancer, and PSA scores are normally evaluated over time in order to track any unusual or sudden change in levels.

9. Understanding prostate problems • After age 40, most men begin to experience some degree of symptoms of prostate disorders, and the likelihood of symptoms arising may continue to increase over time. There are 3 major diseases associated with the prostate. They are prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. It is very important that you understand the symptoms and the warning signs of prostate disease and tell your doctor about any that you experience. Even in the absence of urinary symptoms your doctor may perform periodic prostate exams and regularly monitor your prostate specific antigen (PSA) level.

10. Prostatitis • Prostatitis is an inflammation of the prostate that can affect men of all ages. Some of the signs and symptoms include fever and chills, lower pelvic pressure and pain in the pubic area, pain during urination, and painful or uncomfortable feeling before or during ejaculation. Prostatitis is generally treated with antibiotics.

11. Benign Prostatic Hyperplasia • Benign prostatic hyperplasia (BPH), commonly referred to as enlarged prostate, is a non-cancerous enlargement of the prostate that can cause bothersome urinary symptoms and have a significant impact on the quality of life of a sufferer. Urinary symptoms include increased frequency, urgency, and difficulty urinating.

12. Enlargement of the prostate gland and PSA levels • An enlargement of the prostate is one of the common causes of urinary problems. PSA levels greater that 1.5 can indicate a continued enlargement of your prostate and an increased risk of worsening of urinary symptoms, acute urinary retention, and surgical interventions over time.

13. Prostate Cancer

14. What is Prostate Cancer • Prostate cancer is cancer of the prostate gland in which cells grow out of control within the body, invading and destroying tissues and organs in the prostate. This can spread to other parts of the body, including the bladder, colon, rectum, and bone. Routine blood tests and physical exams can help screen for prostate cancer at its earliest stages. Only your physician can diagnose prostate cancer.

15. Symptoms associated with prostate cancer • Some of the symptoms associated with prostate cancer are dull pain in the lower pelvic area; frequent urination; problems with urination such as the inability to urinate, pain or burning when urinating, weakened urine flow, blood in the urine or semen; painful ejaculation; general pain in the lower back, hips or upper thighs; loss of appetite and/or weight; and persistent bone pain.

16. How is prostate cancer diagnosed? • Prostate cancer is diagnosed from the results of a biopsy of the prostate gland. If the digital rectal exam of the prostate or the PSA blood test is abnormal, prostate cancer is suspected. A biopsy of the prostate is usually then recommended. The biopsy is done from the rectum (trans-rectally) and is guided by ultrasound images of the area. A small piece of prostate tissue is withdrawn through a cutting needle. A pathologist then examines the tissue under a microscope for signs of cancer in the cells of the tissue.

17. Grading of a cancerous tissue: Gleason Scale • When prostate cancer is diagnosed on the biopsy tissue, the pathologist will then grade each of two pieces of the tissue from 1 to 5 on the Gleason scale. The scale is based on certain microscopic characteristics of the cancerous cells and reflects the aggressiveness of the tumor. The two scores are then added together. Sums of 2 to 4 are considered low, indicating a slowly growing tumor. Sums of 5 and 6 are intermediate, representing an intermediate degree of aggressiveness. Sums of 7 to 10 are considered high, signaling a rapidly growing tumor with the worst prognosis (outcome). Gleason scores can be helpful in guiding treatment that is based, at least in part, on the aggressiveness of the tumor.

18. Staging of prostate cancer:Tumor, Nodes and Metastasis (TNM) Classification • A system for staging prostate cancer is called the tumor, nodes, and metastasis (TNM) classification. Stage T1 describes a minimal cancer that can neither be palpated (felt) on physical examination nor seen by imaging techniques. Stage T2 refers to a larger cancer that may be palpated, but that still is confined (localized) to the prostate gland. T3 describes cancer that extends just beyond the capsule (coat) of the prostate, and T4 describes cancer that is fixed to the surrounding tissues. Stage N1 signifies a spread to the nearby (pelvic) lymph nodes and M1 is for distant spread (metastasis), for example, to the bones, liver, or lungs.

19. Stages and Treatments of Prostate Cancer Stages Characteristics Type of Treatment T1 or T2 Localized in the prostate Surgery, radiation therapy (radiotherapy) T3 or T4 Locally advanced Radiation therapy; combination of hormonal therapy and radiation N+ or M+ Spread to pelvic lymph nodes (N+) or distant organs (M+) Hormonal therapy, experimental approaches Type of Treatment

20. Making Treatment decisions • Each one of three characteristics, tumor stage, Gleason score and PSA, is important, and a “bad reading” for any one of them will effect the treatment options and chances of success of treatment. The three factors are combined to form three “risk groups” which guide your doctor in your management.

21. Group One: Favourable risk • This group includes those tumors, which are stage T1 or T2a(involving half a lobe or less of the prostate), with a Gleason score of 6 or less, and a PSA reading of 10ng/ml or less. Hormone therapy is seldom indicated because there is a very low risk of these cancers having spread elsewhere. If your prostate size is not too large, brachytherapy is an excellent option. External beam radiotherapy is also a good choice, and may be better for you if you have a large prostate, or if you already have difficulties passing urine(slow stream, getting up a lot at night).

22. Group Two: Intermediate risk • This group includes tumors, which are slightly larger, T2b, or has a Gleason score of 7, or have a PSA reading between 10 and 20ng/ml. Since these tumors are somewhat more aggressive, there is a greater chance of spread through the capsule of the prostate into the adjacent tissues. Because the dose from brachytherapy is so tightly focused on the prostate and only extends 2-3mm beyond the prostate, it is not generally considered appropriate for tumors in this group, although it may be used as a “boost” in combination with a short course of external radiotherapy. Newer radiotherapy techniques such as 3 dimensional conformal radiotherapy, and intensity-modulated radiotherapy (IMRT) allow a highly effective dose to be delivered safety(daily for 8 weeks).

23. Group Three: High Risk • This group includes tumors which are either locally advanced, or have a PSA higher than 20 at the time of diagnosis, or are aggressive looking under the microscope with Gleason scores of 8, 9 or 10. Since these tumors have a tendency to seed elsewhere early on, treatment will often be directed not only at the prostate, but will also include a prolonged period of hormone therapy which will suppress microscopic spread of the cancer to lymph nodes or bone. The radiotherapy may include a wider field radiotherapy than group two to cover pelvic lymph nodes, but it will almost certainly be combined with 2-3 years course of “hormone therapy”.

24. Prostate Brachytherapy

25. History • Started in the 1900’s by physicians at New York’s Sloan Kettering Memorial Cancer Center. • Used an incision into the abdomen to expose the prostate gland. • Using their hands they guided surgical needles, inserting radioactive seeds one by one into the prostate gland. • Because they could not see inside the prostate, seeds were placed unevenly. • This led to later abandonment of this procedure.

26. Along Comes Ultrasound Technology

27. Ultrasound Technology • In the early 1980’s Dr. Hans Holm of Denmark begins applying a new technology of transrectal ultrasound. This coupled with computerized imaging software allows a major step forward in the development of prostate brachytherapy. • In 1985, Dr. John Blasko and Dr. Haakon Ragde introduce ultrasound-guided prostate implantation to the United States.

28. Brachytherapy Today • Today prostate brachytherapy involves the permanent implantation of 90 to 140 tiny radioactive seeds into the prostate, which then, over the subsequent 6 months, deliver an intense focused dose of radiation to the prostate. The seeds remain permanently. After they have completed their job however, they become inert.

29. Who is Eligible? • The Cancercare Ontario Evidence-based Guideline recommends that this form of treatment be applied only to those men with: • T1c/T2a tumors, which either aren't palpable (felt) on rectal exam, or are palpable as small nodules. • A Gleason score less than or equal to 6. • A presenting PSA less than 10 ng/ml • Outside these guidelines, there's considerable risk that prostate cancer cells have spread into tissue surrounding the prostate. Because radioactive seed implants have a very short range, any tumour cells located outside the prostate may not receive a sufficient dose to be eradicated.

30. Technical Considerations • L prostate size (< 60 cc). Over 500 implants have been performed at the Princess Margaret Hospital of the University Health Network. If the patient has a bigger prostate or has had hormones to shrink his prostate, there is an increased risk of prostate swelling after the implant. The more the swelling, the longer it takes to resolve. • no previous TURP ( less tissue to implant) • pubic arch configuration( hinders the needles and proper seed placement).

31. Pubic Arch Interference

32. Brachytherapy: Advantages • Personal : • simple outpatient procedure( Typically, the seed implant takes about two hours and can be done under either general or spinal anesthesia) • Avoids lengthy hospitalization • rapid return to normal activity • comparable 10 year outcome • perceived as low morbidity

33. After Deciding on Brachytherapy The volume study is the first step. • Cross sectional images of the prostate are taken every 5mm and re-assembled on a computer to make a three- dimensional model of the prostate. • Exact placement of each seed can then be determined. • The team (doctor, physicist and dosimetrist) then takes a created map of the prostate into the operating room. This map is followed closely.

34. Volume Study Geometry

35. Contouring And Planning

36. Template Used to Guided Seed Insertion

37. The Procedure

38. Urinary Morbidity: PMH • Acute urinary retention :16% • Independent of D90, V100, V200 and urethral dose, AUA score • Depends on volume: 39.3 cc vs 33.8 p=0.002 • Depends on # of seeds: 112 vs 102 p=0.004

39. Side Effects • Tenderness and bruising which can last 3-7 days in the perineal area, can feel like one is sitting on a golf ball • Burning sensation while urinating • Blood clots in the first few days following implant, urine is strained for 3 days following implant • Frequency and urgency • In extreme cases--urinary retention requiring catheterization • Rarely are there complications to the bowel and rectum

40. Medications • Flomax-starts 7 days before implant and must continue for at least 3 months post implant, improves urinary stream and bladder emptying by relaxing the smooth muscle around the bladder neck • Cipro- an antibiotic, is taken for 1 week starting the day of the implant • Pyridium-taken 3 times a day for the first 2 weeks following implant, this medication lessens the burning sensation and feeling of urgency • Mobicox- reduces inflammation from the implant, taken for at least one week to one month • Tylenol-Extra Strength or with Codeine--relieves pain from implant, use only as needed

41. Management of Acute Urinary Retention • In-dwelling Foley x 3 - 5 days • Don’t stop the Flomax • Trial of voiding (measure PVR ! ) • Teach ISC • Supra pubic if can’t do ISC • Wait 8- 12 months before TURP (minimal)

42. Management of Acute Urinary Morbidity • Patience!!! • Irritative/obstructive symptoms (high IPS score): •  blockers (Flomax, dose response) • NSAID’s, cox-2 inhibitors better • short course steroids

43. Follow Up • Done at 1 month • Every 2-3 months for first year • 3-4 Months in second year • Every 6 months thereafter • DRE,PSA and bladder function at 6 months • Biopsy at 2 year mark suggested

44. Potency • @ 6 Years: 92% (Merrick, 2002, n=209 incl Viagra) • @ 5 Years: 85% (Sharkey, 2000, n=1048) • @ 3.5 Years: 90% ( Scherr, 1998, n=692) • @ 2 Years:78% (Stone, 2000, n=419) • Combined with NHT @ 2 years : 50% (additional 25% partial) (Sanchez-Ortiz, 2000, n=171)

45. Brachytherapy Results for Favourable Risk Patients • Negative biopsy @ 2 years: 87-95% • Negative biopsy @ 5 yrs: 86-93% • Negative biopsy @ 10 yrs: 71-87%

46. Summary Prostate brachytherapy is a highly effective form of treating early stage prostate cancer and involves the permanent implantation of 90 to 140 tiny radioactive seeds into the prostate. It offers men an alternative to radical surgery and can be performed as an outpatient procedure with considerably less impact on urinary and sexual function. Fifteen years experience with brachytherapy and results for 1000’s of men have indicated that it has similar efficacy to surgery. The favorable side effect profile however makes it an attractive and highly sought-after form of treatment. In 2003, it surpassed radical surgery as the treatment of choice for newly diagnosed localized prostate cancer in the United States.