Clinical Oncology - Genitourinary: Prostate Cancer

Prostate cancer is the ____ malignancy in males in the US, with __ in __ men having prostate cancer in their lifetime

most common; 1, 9

It is the ___ leading cause of cancer-related deaths among men in America

second

What is the average age of diagnosis?

More than 60% of prostate carcinomas occur in men age 65 years and older, with an average age of diagnosis at 66 years old

What race is prostate cancer most common in?

Black men have the highest incident rates

What are some negative prognostic indicators?

Stage and Differentiation: larger and less differentiated tumours are more aggressive and have higher incidence of lymphatic and distant metastases

Race: black men are likely to be diagnosed at advanced stage and have highest mortality rate

PSA Levels: lower the level post-treatment, lower the likelihood of PSA rising

Is lymph node dissection used as a staging tool?

No, due to the use of PSA levels. It can help determine risk of spread to lymph nodes.

Describe the anatomy of the prostate

Walnut shaped organ consisting of fibrous, glandular and muscular tissue. It surrounds the urethra. It is attached anteriorly to the pubic symphysis, anterior to rectum and anterior-inferior to seminal vesicles.

Where do prostate carcinomas typically develop?

Develop in peripheral glands and are usually multifocal. Benign prostatic hypertrophy usually arises centrally.

How do prostate carcinomas typically spread?

Extend through capsule of gland and invade periprostatic tissues, seminal vesicles, bladder + rectum if left untreated

Describe the lymphatic spread of prostate carcinomas

Periprostatic and obturator nodes, external and iliac nodes, common iliac, and para-aortic nodes

What is the clinical presentation of prostate cancer?

Typically asymptomatic until it reaches significant size. Signs and symptoms may include decreased urinary stream, frequency, dysuria, difficulty starting urination, nocturia, hematuria.

*These symptoms can be caused by benign prostatic hyperplasia

What is included in the physical exam?

DRE, to palpate prostate and feel for abnormalities and enlargements

How is a diagnosis of prostate carcinoma obtained?

Transuretral ultrasound guided biopsy where 12+ core biopsies are taken

What is the screening for prostate carcinoma?

Annual DRE in men over 50 years, and routine PSA in men over 50 years

What is the most common presentation of prostate cancer now with increased screening and awareness?

Elevated PSA levels with no palpable disease (stage T1c)

How can PSA be used other than in detecting prostate cancer?

It can be used in the selection of patients for treatment and evaluating response after treatment. There is a close relation between PSA levels and clinical/pathological stage and involvement of lymph nodes, especially when used with Gleason score.

Describe T1 lesions

T1: not detectable on DRE

T1a: well-differentiated and incidentally found during transurethral resection of prostate (TURP) (<5% of resected tissue)

T1b: large volume and usually there is multifocal involvement (>5% of resected tissue)

T1c: identified via biopsy due to elevated PSA levels

Describe T2 lesions

T2: palpable and confined within capsule

T2a: one lobe

T2b: involve both lobes

T2c: both sides of prostate

Describe T3 lesions

T3: more locally extensive, beyond edges of prostate or into seminal vesicles

T3a: extracapsular extension, unilateral or bilateral

T3b: seminal vesicle invasion

Describe T4 lesions

Fixed to pelvic sidewall or invades adjacent structures (rectum, bladder)

What is M1a, M1b, and M1c disease?

M1a: non-regional lymph nodes

M1b: bone

M1c: other sites

What are the treatment techniques involved in prostate cancer?

Observation, prostatectomy, hormonal therapy, chemotherapy, radiation

What are treatment options for tumours limited to the prostate?

Radical prostatectomy and radiation therapy are both equally effective treatments

When would active surveillance be an option for treatment?

Younger patients (65-75) with small, well-differentiated tumours

Patients older than 75 years old

T1 to T2 tumours, Gleason score 2-6, PSA < 10 ng/mL, and life expectancy greater than 10 years

Any stage disease with life expectancy less than 5 years

What treatment option is available for T1a tumours?

No treatment is an option, as it takes many years before disease becomes a clinical issue

Who is a good candidate for a prostatectomy?

Patients with resectable T1/2 tumours in good health with a life expectancy of at least 10 years

What has changed about prostatectomies over the years?

Bilateral nerves are spared which results in a lower incidence of impotence

What is the treatment approach for T3 or high risk prostate cancer?

Due to increased risks of disease progression, radical prostatectomy alone is not sufficient for disease control and with secondary form of treatment is needed, such as radiation therapy and hormonal therapy

How does hormonal therapy play a role in treatment of prostate cancer?

Decreases proliferation of prostate cancer cells by cutting off testosterone supply. It can be used to reduce metastatic tumour burden and palliative symptoms, decrease recurrence.

What is one of the main hormonal therapy drugs?

Maximal androgen blockade (MAB)

What is maximal androgen blockade (MAB)?

Injection of luteinizing hormone releasing hormone (LHRH) receptor blockers given once monthly or every 3 months to stop production of testosterone

What are anti-andogrens for?

Block testosterone from reaching prostate and can be taken daily via pills

When do patients stop hormone therapy?

When PSA levels drop to low enough levels and as long as they continue to be monitored

When is hormonal therapy used?

It is used in addition to radiation therapy in localized prostate cancer with intermediate or high risk of recurrence, locally advanced, and metastatic cancer. It can be administered short-term (2 months pre and during treatment) in bulky Gleason score 2 to 6 tumours or long term (2 years) in Gleason score 8 to 10.

When is chemotherapy used in prostate cancer treatment?

Prostate cancer that has spread outside of the prostate or if disease is not responding to hormone therapy

What is high risk prostate cancer?

PSA > 20 ng/mL

Gleason score 8-10

Clinical stage T2c

What is low risk prostate cancer?

PSA< 10 ng/ml

Gleason score 6 or less

Clinical stage T1c or T2a

What radiation treatment technique was previously used before IMRT/VMAT? Why?

4 field box technique. It was used to treat pelvic lymph nodes, along with the prostate and seminal vesicles. It was believed that pelvic lymph node irradiation was necessary to reduce risk of metastasis.

What was the disadvantage of 4-field box in prostate treatment?

Large field sizes due to lymph nodes and it minimized dose to prostate due to side effects from the bladder and rectum

What are the field borders in the 4-field box technique (prostate and seminal vesicles)?

Superior: midsacrum, spare rectum and small bowel

Inferior: inferior part of prostate with margin

Anterior: 1 cm posterior to pubic symphysis

Posterior: posterior ischium, with shielding of rectal wall

Lateral: 1.5 to 2 cm from pelvic brim

*Small bowel was spared anteriorly, with consideration of external iliac nodes

What are the field borders in the 4-field box technique (prostate, seminal vesicles and pelvic lymph nodes)?

Superior: L5/S1 to cover sacral, common iliac, external and iliac lymph nodes

Inferior: bottom of ischial tuberosities

Anterior: cover pubic symphysis to cover external iliac nodes

Posterior: midway to rectum

Lateral: medial border of iliopsoas muscle to cover iliacs

If CT sim was not available, how was the rectum defined?

Barium or plastic catheter with radiopaque markers

What are the CT sim margins for treatment of prostate cancer?

Superior: below diaphragm

Inferior: mid-femur

What techniques are used to verify the position of the prostate prior to treatment?

Ultrasound imaging (B-mode acquisition technology), injection of SpaceOAR Hydrogel between rectum and prostate, image-guided radiation therapy (IGRT)

What is the purpose of SpaceOAR Hydrogel?

Increases space between prostate and rectum. It remains in body for 3 months and is absorbed into body and excreted during urination. It may be associated with less rectal pain during treatment and less long-term rectal complications.

What radionuclides are used in LDR brachytherahy?

I-125 (half life 60 days)

Pd-103 (half life 17 days)

Cs-131 (half life 9.7 days)

What radionuclides are used in HDR brachytherapy?

Ir-192

What is the common fractionation for HDR brachytherapy?

45.5 Gy/7 fx over 3.5 days (6.5 Gy/fx)

What is the follow-up for brachytherapy?

CT scan after 1 month and every 3 months for the first year

When is interstitial brachytherapy done?

May be used alone, or used as a boost after moderate dose EBRT (45 Gy) for patients with significant risk of tumour extension outside prostate

Describe the Gleason score system

Dominant/primary differentiation pattern and secondary pattern are labeled from grade 1 to 5, and added together to obtain Gleason score of 2 to 10

When is radiation indicated after a prostatectomy?

PSA is undetectable after surgery but margins contain tumour or seminal vesicles are involved

PSA is undetectable immediately after surgery but begins to rise

What is a reason why PSA levels do not drop after surgery? Would radiation therapy be beneficial?

All of the tumour has not been removed. PSA may be detectable due to metastatic disease, so radiation would not be beneficial. Radiation therapy can be applied if it is proven that the only disease present is within surgical bed.

What dose is applied for post-operative patients with microscopic disease with undetectable PSA levels?

64 to 66 Gy, to 70 Gy if PSA levels are rising

What can occur after a prostatectomy that impacts dose coverage?

Bladder and rectum may move into prostate space. Dose levels may be compromised due to bladder and rectum tolerances.

What side effects are associated with a prostatectomy?

Incontinence and sexual impotence

What side effects are associated with radiation therapy for prostate cancer?

Diarrhea, abdominal cramping, rectal discomfort, and on occasion, rectal bleeding

When would proton therapy not be a good option for the treatment of prostate cancer?

If seminal vesicles are to be treated, as it is a posterior structure and would result in increased dose to rectum

Are routine biopsies for follow-up performed post-radiation treatment?

No, as PSA levels are a good indication of recurrent disease and highly correlate with biopsy results. Biopsies are important when local treatment for recurrence is planned, as prostatectomy and reirradiation carry high complication rates, so it is important to ensure local disease is present, as PSA increasing could be due to nodal or distant disease.

When is a palliative dose used for prostate cancer? What dose is used?

50 to 60 Gy may be effective for massive, locally extensive prostate cancer or significant size pelvic nodal disease causing pain, hematuria, urethral obstruction, or leg edema

30 Gy can be used for distant metastases