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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Image of a prostate gland needle biopsy shows a small focus of adenocarcinoma on right side of slide (normal glands on left side). Prostate cancer is the most common noncutaneous cancer in men,[1] with about 161,360 new cases (19% of male cancer cases) and 26,730 deaths (8% of male cancer deaths) predicted in 2017.[2] Accordingly, diagnosis and staging of prostate cancer are critically important.

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

The anatomy of the human male is shown. Which of the following statements is false with regard to the human prostate gland?

  1. It is located inferior to the bladder and anterior to the rectum
  2. It functions as part of the male reproductive system and aids in the formation of spermatozoa
  3. It consists partly of smooth muscles, which aid in the expulsion of semen during ejaculation
  4. It is homologous to the Skene (paraurethral) gland found in women
  5. Prostate cancer is the third leading cause of cancer-related deaths in American men
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: B. It functions as part of the male reproductive system and aids in the formation of spermatozoa.

The prostate is a component of the human male reproductive system[3]; however, spermatogenesis occurs in the seminiferous tubules of the testes.[3,4] The prostate manufactures approximately 20-30% of the seminal volume,[5] and the semen assists in carrying sperm from the testes through the penis during the ejaculatory phase.[4]

In this image, a clinician inserts a gloved and lubricated finger into the rectum during a digital rectal examination (DRE) to palpate the prostate for any unusual lumps or irregularities. The presence of a prostate nodule is an indication for biopsy.

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Image courtesy of the National Cancer Institute (NCI).
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

In your clinic, a male patient notices the graph (shown) of estimated prostate cancer cases and deaths. He asks you what the lifetime incidence of prostate cancer is for a man from the general population.

Which of the following is the most accurate response?

  1. Between 1 in 3 and 1 in 5
  2. 1 in 5
  3. Between 1 in 8 and 1 in 9
  4. 1 in 10
  5. 1 in 42
5 of 28

Image courtesy of the Centers for Disease Control and Prevention (CDC).
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: C. Between 1 in 8 and 1 in 9.

On the basis of 2012-2014 data, the lifetime risk of prostate cancer in the general male population is about 11.6% (1 in 8.6).[2] The incidence of prostate cancer increases with age (36.3% of new cases are in men aged 65-74 years) and in men with a family history of prostate cancer. In black men, both the incidence (188.7 per 100,000 men) and mortality rates (42.0 per 100,000 men) are higher than in men of other races.[2]

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

A 59-year-old male patient undergoing transrectal ultrasonography (TRUS) is found to have an extensive hypoechoic area (arrows) in the right peripheral zone. Before proceeding further, the clinician discusses the risks and benefits of obtaining a prostate biopsy with the patient.

Which of the following is not a common complication of a prostate biopsy?

  1. Fever and pain
  2. Hematospermia
  3. Hematuria
  4. Urinary tract infection
  5. None of the above; all are potential complications
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: E. None of the above; all are potential complications.

Fever, pain, hematospermia, hematuria, and urinary tract infection are all potential complications of a prostate biopsy.[6] In TRUS (shown), an ultrasound probe is inserted into the rectum to assess the prostate when prostate-specific antigen (PSA) levels are elevated or irregular nodules are noted on the DRE.[5] The standard PSA reference range is 0.0-4.0 ng/mL. Normal PSA levels for specific age ranges are 0-2.5 ng/mL for age 40-49 years, 0-3.5 ng/mL for age 50-59 years, 0-4.5 ng/mL for age 60-69 years, and 0-6.5 ng/mL for age 70-79 years.[7] TRUS can also reveal prostatitis and benign prostatic hyperplasia.

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Image courtesy of the NCI / Otis Brawley, MD.
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

On hematoxylin-eosin stain (×300) of TRUS-guided prostate biopsy specimen (shown), two distinct differentiations of prostatic tissues are noticeable when the slide is viewed from the right half to the left.

Which of the following Gleason values (or scores) can most accurately be applied to this tissue?

  1. Gleason values 1 and 2
  2. Gleason values 2 and 3
  3. Gleason values 3 and 4
  4. Gleason values 4 and 5
  5. Gleason values 1 and 3
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: C. Gleason values 3 and 4.

The standard for grading prostate cancer is the Gleason value, which is determined through pathologic evaluation of a prostatectomy specimen and is commonly estimated from prostate biopsy tissue.[8] Prostate cancer patterns are assigned a number from 1 to 5 (ie., from well differentiated to very poorly differentiated); the Gleason value is created by adding the most common pattern grades and the highest-grade patterns. The histologic features in slide 8 revealed a Gleason value of 3 (moderately differentiated cancer) on the right and a Gleason value of 4 (less well-differentiated cancer) on the left. The patient's Gleason value is therefore 7 (3 + 4).

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

An 84-year-old asymptomatic man presents to his doctor for follow-up. His medical record shows that 1 year ago, a prostate biopsy performed by another physician revealed prostate cancer (Gleason 3 + 3 = 6) in one of 12 cores, occupying 5% of the core length. His current PSA level (5.9 ng/mL) is essentially unchanged from 1 year ago. The patient reports no recent urinary complaints, bone pain, or weight loss. He has congestive heart failure (ejection fraction, 20%), persistent atrial fibrillation, and liver cirrhosis. He is currently taking warfarin, metoprolol, spironolactone, benazepril, furosemide, and lactulose. The patient is afebrile, and his blood pressure is 132/82 mm Hg. His pulse rate is 65 beats/min and irregular. The physical examination yields no pertinent findings.

Which of the following is the most appropriate next step in the evaluation of this patient?

  1. Referral for radical prostatectomy
  2. Computed tomography (CT) of the abdomen
  3. Bone scan
  4. Repeat TRUS-guided biopsy
  5. Observation
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Source of image information: NCCN.[6]
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: E. Observation.

For a patient such as this—an older man with very-low-risk prostate cancer and multiple medical comorbidities whose life expectancy is less than 10 years—the National Comprehensive Cancer Network (NCCN) recommends observation.[9] Observation consists of monitoring (including PSA and DRE) no more often than every 6 months, to guide the initiation of palliative androgen deprivation therapy.[9]

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

A 63-year-old man presents to his internist with a screening PSA level of 14.2 ng/mL. On DRE, the clinician notices a distinctly irregular prostatic border. A TRUS image is shown.

In view of the potential for a prostatic malignancy, which of the following is the most appropriate next step for diagnostic purposes?

  1. Nuclear medicine bone scan
  2. Endorectal magnetic resonance imaging (MRI)
  3. TRUS-guided prostate biopsy
  4. Determination of PSA doubling time
  5. Radical prostatectomy
13 of 28

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: C. TRUS-guided prostate biopsy.

On the basis of the clinical findings, the best next diagnostic step is to obtain a TRUS-guided prostate biopsy.[10] The hypoechoic lesion visible in this image, highlighted in blue in the peripheral zone of the gland, is suggestive of cancer. With the development of the PSA screening test in the early 1990s, prostate cancer has been diagnosed earlier in its course.[11] Prostate cancer is most commonly suspected on the basis of elevations on PSA screening tests, abnormalities noted on DRE, or both.[10,11] Most prostate cancers are diagnosed without any abnormalities on examination.

14 of 28

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

A 62-year-old asymptomatic man has no significant past medical history and a smooth-surfaced prostate on DRE. However, his PSA level is 25 ng/mL. TRUS-guided biopsy reveals prostate carcinoma (shown) confined to the prostate, with a Gleason value of 8.

What is the most appropriate next step for this patient?

  1. MRI
  2. CT
  3. Bone scan
  4. Monitoring (surveillance)
15 of 28

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: C. Bone scan.

The tumor is clinically staged as T1cNXMX (IIA); it was identified by needle biopsy that was obtained because of the high PSA level (>20 ng/mL), and nodal spread and distant metastasis cannot be assessed with the information given.[9] The patient also does not have T2, T3, or T4 clinical disease. Therefore, a bone scan is the best next step for staging workup.[9] The isotopic bone scans shown reveal diffuse metastases and demonstrate a "superscan" appearance (intense symmetric activity in the bones with diminished renal/soft-tissue activity[12]); note the absence of renal excretion of radioactive tracer. Almost all prostate cancer patients are initially diagnosed with T1c disease, and almost none have any symptoms related to the prostate or to prostate cancer.[13]

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

The table shown lists issues associated with DRE and PSA screening.[11] Screening guidelines from different organizations agree on the importance of engaging patients in an informed discussion of the risks and benefits of screening, but vary in their recommendations of the age at which to start screening for men at average risk; 50 years, according to the NCCN[10] and the American Cancer Society (ACS)[11]; 55 years, according to the American Urological Society[14] and the U.S. Preventive Services Task Force.[15] Recommended retesting frequency depends on the PSA level; for example, the ACS advises that if the PSA level is less than 2.5 ng/mL, retesting may need to be done only every 2 years.[11] The recommended age for discontinuing screening also varies, from 70 to 75 years.[10,11]

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Image courtesy of Wikimedia Commons / Steven Fruitsmaak.
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Two years ago, a 69-year-old man presented with worsening complaints of urgency, incontinence, nocturia, and weak urinary stream. At that time, his PSA level was 3.3 ng/mL, and he was started on tamsulosin. Finasteride was recently added to help control his symptoms; however, the symptoms persisted. A DRE did not reveal an enlarged prostate or any masses. A suprapubic transvesical prostatectomy was performed. Tissue analysis incidentally revealed prostate cancer in 2% of the prostate tissue with a Gleason value of 4. No lymph node involvement was found. Further imaging did not reveal any metastasis.

Which stage is this patient's cancer?

  1. Stage I
  2. Stage II
  3. Stage III
  4. Stage IV
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: A. Stage I.

Clinicians use prostate cancer staging not only to categorize the risk of the cancer spreading beyond the prostate but also to evaluate the potential for administering local therapies, including surgery and radiation.[3,8,9,16] Staging also employs the Gleason value for grading. In stage I disease, prostate cancer is confined to the prostate. The table shown details the tumor-node-metastasis (TNM) staging system for prostate cancer, which evaluates the size of the tumor, the involvement of lymph nodes, and the presence of any metastasis.[3,8,9,16] A tumor that is not clinically apparent is staged T1; a tumor that is confined to the prostate is staged T2; a tumor that extends beyond the prostate capsule is staged T3.[3,8,9,16]

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Table adapted courtesy of NCI.
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Prostate cancer is categorized into four stages on the basis of the TNM system, the patient's PSA level, and the Gleason value.[3,8,9,16]

20 of 28

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

A 74-year-old man presents to an urgent care clinic with a complaint of right-side pelvic pain. He also complains of back pain that has been increasing in severity over the course of the past year. Radiography of his pelvis is performed (shown).

Which of the following lesions are evident on this pelvic radiograph?

  1. Osteoblastic metastases
  2. Sclerotic metastases
  3. Osteolytic metastases
  4. Both osteoblastic metastases and sclerotic metastases
  5. None of the above
21 of 28

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: D. Both osteoblastic metastases and sclerotic metastases.

Bony metastasis is common with prostate cancer; it presents as multiple osteoblastic lesions, as seen on slide 20.[17] Osteolytic prostate metastases can occur as well. On plain radiography, osteoblastic lesions appear hyperdense (bright/white) whereas sclerotic or lytic lesions appear hypodense (dark/black). Tumors from the prostate, breast, lung, thyroid, and kidney are the cancers that most commonly metastasize to bone.[17,18] Metastases that present as mixed lytic-sclerotic lesions typically originate in the lung and breast. A radionuclide isotopic bone scan after injection of methylene diphosphonate (MDP) technetium-99m (shown) is the standard imaging modality used to assess for potential bone metastases from prostate cancer.[8] Multiple areas of increased radionuclide tracer activity from metastatic prostate cancer are present on this bone scan.

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

A DRE performed on a 73-year-old man reveals a normal-sized and mobile prostate, but a nodular mass within the borders of the prostate gland is palpable (arrow). His PSA level is 15.5 ng/mL. Soon thereafter, the patient undergoes TRUS evaluation, and a biopsy reveals adenocarcinoma of the prostate with a Gleason value of 9. CT does not reveal any spread of the cancer outside of his prostate.

What is the stage of this patient's prostate cancer?

  1. Stage I
  2. Stage II
  3. Stage III
  4. Stage IV
23 of 28

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: B. Stage II.

In stage II prostate cancer (shown), the tumor has advanced and is of a higher grade than stage I disease. However, it does not extend beyond the prostate.[3,8] The tumor can be palpated on DRE, and it can often be seen on TRUS. Stage III disease involves extension of the primary tumor outside of the prostate capsule.[3,8]

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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

A 72-year-old man with a PSA level of 18.5 ng/mL undergoes a prostatic biopsy; histopathologic examination reveals prostate cancer with a Gleason value of 7. MRI is performed for staging purposes. The axial T2-weighted image (left) shows a low-intensity lesion primarily involving the peripheral zone at the base with obliteration of the rectoprostatic angle (arrowhead). Definitive surgery reveals extracapsular extension of the cancer but no seminal vesicle or lymph node involvement.

What is the stage of this patient's prostate cancer?

  1. Stage I
  2. Stage II
  3. Stage III
  4. Stage IV
25 of 28

Image courtesy of the NCI.
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: C. Stage III.

Slide 24 showed a lesion in the left peripheral zone of the prostate with extracapsular extension. The surgical pathology confirmed the extracapsular spread (pT3aN0), indicative of stage III disease. Stage III prostate cancer involves extracapsular invasion that may involve the seminal vesicles but has not spread beyond the seminal vesicles.[3,8] It also includes tumors with documented spread to the seminal vesicles (pT3b). Stage IV disease (shown) may include T4 (with extension to the bladder or rectum, resulting in a gland that appears "fixed" on physical examination) or involvement of nearby lymph nodes.[3,8]

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Image courtesy of Wikimedia Commons.
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

A 70-year-old man presents with advanced prostate cancer with diffuse osteoblastic bony metastases (arrows) to the spine, pelvis, and femur, as seen on this anteroposterior abdominal radiograph.

Which of the following are common symptoms of advanced or recurrent prostate cancer?

  1. Loss of appetite and weight loss
  2. Back pain and bony pain (without fractures)
  3. Suppression of the bone marrow
  4. Compression of the spinal cord
  5. All of the above
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Image courtesy of Medscape
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Prostate Cancer: Diagnosis and Staging

Roman Kleynberg, MD; Mitchell Gross, MD, PhD | May 4, 2017 | Contributor Information

Answer: E. All of the above.

Advanced prostate cancer is often associated with loss of appetite, weight loss, back pain, and bony pain, (without fractures), suppression of the bone marrow, and compression of the spinal cord.[19] This CT scan at the level of the kidneys indicates extensive para-aortic lymphadenopathy (arrows) secondary to advanced prostate cancer.

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