1. Mandair D, Rossi RE, Pericleous M, et al. Prostate cancer and the influence of dietary factors and supplements: a systematic review. Nutr Metab (Lond). 2014 Jun 16;11:30.
  2. Odom BD, Mir MC, Hughes S, et al. Active surveillance for low-risk prostate cancer in African American men: a multi-institutional experience. Urology. 2014 Feb;83(2):364-8.
  3. Fütterer JJ, Briganti A, De Visschere P, et al. Can Clinically Significant Prostate Cancer Be Detected with Multiparametric Magnetic Resonance Imaging? A Systematic Review of the Literature. Eur Urol. 2015 Feb 2. [Epub ahead of print]
  4. AC, Coakley FV, Qayyum A, et al. Peripheral zone prostate cancer: accuracy of different interpretative approaches with MR and MR spectroscopic imaging. Radiology. Jan 2008;246(1):177-84.
  5. Harnden P, Shelley MD, Clements H, et al. The prognostic significance of perineural invasion in prostatic cancer biopsies: a systematic review. Cancer. 2007 Jan 1;109(1):13-24.
  6. Roghmann F, Antczak C, McKay RR, et al. The burden of skeletal-related events in patients with prostate cancer and bone metastasis. Urol Oncol. 2015 Jan;33(1):17.e9-18.
  7. Bubendorf L, Schöpfer A, Wagner U, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000;31(5):578-583.
  8. Mohiuddin JJ, Baker BR, Chen RC. Radiotherapy for high-risk prostate cancer. Nat Rev Urol. 2015 Mar;12(3):145-154.
  9. Basch E, Loblaw DA, Oliver TK, et al. Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol. 2014 Oct 20;32(30):3436-48.

Image Sources

  1. Slide 2:
  2. Slide 3:
  3. Slide 4:
  4. Slide5:
  5. Slide 6:
  6. Slide 7:
  7. Slide 8:
  8. Slide 9:
  9. Slide 10:
  10. Slide 11:
  11. Slide 12:
  12. Slide 13:
  13. Slide 14:
  14. Slide 15:
  15. Slide 16:
  16. Slide17:
  17. Slide 18:
  18. Slide19:
  19. Slide20:

Contributor Information


Lars Grimm, MD, MHS
Clinical Associate
Department of Diagnostic Radiology
Duke University Medical Center
Durham, North Carolina

Disclosure: Lars Grimm, MD, MHS, has disclosed no relevant financial relationships.


Edward David Kim, MD, FACS
Professor of Surgery
Division of Urology
University of Tennessee Graduate School of Medicine
Knoxville, Tennessee

Disclosure: Edward David Kim, MD, FACS, has disclosed no relevant financial relationships.


Close<< Medscape

Advanced Prostate Cancer: Signs of Metastatic Disease

Lars Grimm, MD  |  April 16, 2015

Swipe to advance
Slide 1

Prostate cancer is the second leading cause of cancer-related deaths in the United States and the most commonly diagnosed cancer in American men. Most of these deaths are due to advanced-stage disease secondary to lymphatic, hematologic, or contiguous local spread. An understanding of the patients at risk for advanced disease, diagnostic options, treatment options, and prognostic factors is critical for clinicians. The bone scan shown is of a patient with metastatic widespread prostate cancer.

Image courtesy of Lars Grimm, MD.

Slide 2

The criteria for TNM staging of prostate cancer are shown. The majority of prostate cancer (~80-90%) is localized due to better efforts at screening and early diagnosis; this has been associated with a decline in mortality rates. Prostate cancer is more common in men who smoke, black males, and men who consume diets high in animal fat or chromium.[1] Black males are more likely to have cancer that is more aggressive, leading to advanced disease.[2]

Image courtesy of Medscape.

Slide 3

The Gleason system (shown) can be used to grade prostate cancer. It is based on histologic evaluation of tumor biopsy specimens. The sum of the most predominant grade and the second most common grade determines the final score. Patients with a Gleason score of 6 or greater are more likely to progress to advanced cancer.

In what part of the prostate gland is cancer most likely to develop?

  1. Central gland
  2. Central zone
  3. Peripheral zone
  4. Transition zone

Image courtesy of Wikimedis Commons / NIH.

Slide 4

Answer: C. Peripheral zone

The prostate is divided into several glands and zones. The central gland and transitional zone comprise the central zone. Benign prostatic hypertrophy with hyperplastic nodules develop in the central zone. The peripheral zone comprises the periphery of the prostate and is the site of approximately 70% of prostate cancer. A transrectal ultrasound image of the prostate (shown) demonstrates a peripheral zone cancer (arrow). Transrectal ultrasound is typically reserved for biopsy and brachytherapy seed placement instead of as a screening tool because the sensitivity and specificity are only around 40-50%.

Image courtesy of Medscape.

Slide 5

For patients with a diagnosis, magnetic resonance imaging (MRI) has become an increasingly important modality for staging and the detection of locally advanced disease. The use of MRI for detection is not cost-effective. The use of an endorectal coil combined with a pelvic coil significantly improves signal acquisition. The coronal MRI image shown demonstrates a large locally advanced prostate cancer (arrow).

Image courtesy of

Slide 6

Advanced MRI techniques have improved the ability to detect and define the extent of disease, beyond standard T1 and T2 imaging. It is often best to delay MRI until 8-12 weeks after biopsy to avoid confusion from post-biopsy hematomas. The MRI image on the left demonstrates the restricted diffusion commonly seen in prostate cancer. The image on the right demonstrates increased K trans (yellow coloring) due to microvascular permeability.

Image courtesy of

Slide 7

Magnetic resonance (MR) spectroscopy is an advanced imaging modality that shows promise as a supplement to traditional MRI techniques.[3] Experimental results to date have been mixed. MR spectroscopy provides information about the relative concentration of cellular metabolites in the prostate, such as citrate and choline. Citrate is a marker of normal prostatic tissue, while an increased concentration of choline is suggestive of a tumor lesion.[4] Prostate cancer will demonstrate a choline peak (red arrow) that is greater than the citrate peak (yellow arrow).

Where are the neurovascular bundles typically located on an axial MRI sequence?

  1. 12 and 6 o'clock
  2. 10 and 2 o'clock
  3. 5 and 7 o'clock
  4. 3 and 9 o'clock

Image courtesy of

Slide 8

Answer: C. 5 and 7 o'clock

Perineural invasion refers to tumor that is tracking along or surrounding a nerve (arrow) in the perineural space. Perineural spread is a major mechanism of extension from the prostate into the surrounding soft tissues. It may increase the likelihood of cancer recurrence.[5] A key factor to identify on prostate MRI is the presence of invasion of the seminal vesicles and the neurovascular bundle.

Slide 9

MRI is very useful for the identification of locally advanced disease. Extracapsular spread, neurovascular invasion, local lymph node involvement, and local organ invasion can all be detected on MRI. The sagittal MRI image shows invasion into the bladder base (arrow). Invasion of the bladder would signify a T4 cancer, which corresponds with stage IV disease, regardless of the presence of additional sites of disease.

Image courtesy of

Slide 10

Prostate cancer most commonly develops osseous metastatic disease. These lesions typically appear as sclerotic lesions, although lytic lesions may appear in cases of poorly differentiated tumors. The abdominal radiograph shown demonstrates diffuse osseous metastatic disease (arrows). Plain radiographs may be ordered in patients with acute pain to evaluate for fracture, but typically bone scans, computed tomography (CT), or MRI are used to evaluate for osseous metastatic disease.

Slide 11

Technetium 99m bone scans are very sensitive for the detection of osseous metastatic disease. However, they are nonspecific because fractures, inflammation, or infection can all present with increased radiotracer uptake. The anterior and posterior images on the left demonstrate multifocal areas of increased tracer uptake from metastases. In patients with diffuse osseous metastatic disease, the entire skeleton takes up tracer and no tracer is seen in the soft tissues. This is referred to as a superscan, as seen in the anterior and posterior images on the right (note the lack of renal or soft tissue activity).

Image courtesy of

Slide 12

Although the osseous metastatic lesions are sclerotic, the bone is actually more brittle and prone to fracture. Patients with vertebral body metastases are at risk of developing spinal fractures and cord compression.[6] Clinicians should have a low threshold for CT or MRI imaging for patients with osseous metastatic disease who present with trauma. The sagittal CT image shows sclerotic metastases in the dens, C6, and T1 vertebral bodies, which are at risk for fracture and cord impingement.

Image courtesy of

Slide 13

In addition to being susceptible to fracture, osseous metastases can also cause extrinsic compression of the confined spinal canal. The sagittal MR image shown demonstrates sacral metastases (arrow) that are compressing the lower spinal roots, leading to cauda equina syndrome.

CT scan for prostate cancer is primarily utilized to evaluate what structures?

  1. Brain
  2. Cardiac involvement
  3. Abdominal organs
  4. Seminal vesicles

Image courtesy of

Slide 14

Answer: C. Abdominal organs

The role of CT in the evaluation of prostate cancer is predominately for soft tissue involvement. Bone scans are more sensitive for the detection of osseous lesions and MRI is better for local staging. The CT image shown demonstrates extensive abdominal lymphadenopathy (arrows) from advanced prostate cancer. Bulky adenopathy may lead to hydronephrosis from ureteral obstruction. After the bones, what is the most common site of metastatic disease?

  1. Brain
  2. Lungs
  3. Liver
  4. Kidneys

Image courtesy of Medscape.

Slide 15

Answer: B. Lungs

The lungs (~50%) are the most common site of metastatic disease after the bones (~90%), followed by the liver (~25%), pleura (~20%), and adrenals (~10%).[7] Spinal metastatic disease typically precedes involvement at other sites. Spinal involvement decreases from the lumbar to the cervical spine consistent with upward metastatic spread along spinal veins. The chest radiograph shown demonstrates diffuse pulmonary metastatic disease.

Image courtesy of

Slide 16

Patients with known metastatic disease must be carefully evaluated if they develop neurologic symptoms. Most metastases to the head are via the skull and typically stop at the dural margin. Invasion of the neural axis is rare but may lead to devastating complications. The CT image shown demonstrates invasion of the brain parenchyma with associated hemorrhage (arrow).

Image courtesy of

Slide 17

Treatment options for patients with advanced prostate cancer differ whether the disease is widely advanced or locally advanced (T3). For locally advanced disease, combination therapy is typically offered. Survival in men with T3-4N0M0 disease is improved with a combination of external radiation with androgen ablation for 6 months.[8] Brachytherapy (shown) may be combined with external beam radiation therapy (EBRT) and androgen-deprivation therapy (ADT). ADT typically begins several months before radiation is initiated and continues for several months or years afterwards; however, the optimum timing and duration remains unclear. ADT is associated with anhedonia, osteoporosis, anemia, weight loss, fatigue, and depression. Fortunately, these symptoms typically resolve after therapy is ultimately discontinued.

Image courtesy of

Slide 18

The most common case of advanced prostate cancer is a patient with a rising PSA who failed initial local therapy. Therapy must be tailored based on the local therapy previously attempted, the patient's life expectancy, likelihood of cure, patient's quality of life, and risk of treatment-induced morbidity. Therapeutic protocols are not well established but treatment options include luteinizing hormone-releasing hormone (LHRH) agonists, antiandrogens, and gonadotropin-releasing hormone (GnRH) agonists. ADT has traditionally been thought of as a palliative agent, as most men progress to hormone-refractory prostate cancer. Hepatic prostate cancer metastases are shown on this abdominal CT scan.

Image courtesy of

Slide 19

For patients who become resistant to androgen ablation, the treatment options are very challenging. Although somewhat controversial, most oncologists recommend continuing hormone suppression, because some cells may still be hormone sensitive.[9] Nonchemotherapeutic options for palliation and to improve quality of life include megestrol, corticosteroids, radiation therapy (external beam radiation therapy shown), bisphosphonates, estrogen, and nonsteroidal antiandrogens. Therapeutic options include docetaxel, sipuleucel-T, abiraterone acetate, enzalutamide, cabazitaxel, and mitoxantrone. It can be difficult to determine the sequence and timing of delivery for these agents.

Image courtesy of Medscape.

Slide 20

Despite the steady decline in the incidence of newly diagnosed metastatic prostate cancer and microscopic lymph node metastasis, the risk of extraprostatic disease in patients with clinically localized disease remains high (30-60%). Approximately 50% of patients with clinically localized prostate cancer are estimated to progress despite initial treatment with intent to cure. Although a Gleason grade of 7 or less is associated with a better prognosis than a grade of 8 or more, if the PSA level rise occurs after 2 years following local treatment, the associated survival likelihood is greater than if the rise occurs before 2 years. If given enough time, all patients with metastatic disease become resistant to androgen ablation. The median time to symptomatic progression after a rise in the PSA level of more than 4 ng/mL is approximately 6-8 months, with a median time to death of 12-18 months. Once the patient exhibits symptoms, the median survival is less than 1 year.

Image courtesy of Medscape.

< Previous Next >
  • Google+
  • LinkedIn