Assistance in the composition of this article was provided by Dr. Udo Schmeidl, staff radiologist, Seattle Radiologists; and by Dr. Jim Borrow, formerly staff radiologist, First Hill Diagnostic Imaging, Seattle, now a consultant in MRI radiology.
The appropriate staging protocol after the diagnosis of prostate cancer is undergoing progressive evolution in keeping with the increasing sophistication of imaging technology. A recent article in the American Journal of Radiology reports that a multiparametric MRI of the prostate and pelvis combined with an MRI of the lumbar spine serves well as a single staging study for high-risk intermediate and high-risk prostate cancer. This one study can supplant the current customary CT of the pelvis often in conjunction with a Technetium or NaF PET/CT imaging of the skeletal system.
“Identification of Bone Metastases With Routine Prostate MRI: A Study of Patients with Newly Diagnosed Prostate Cancer,” by Woo et al, AJR, June 2016, reports on 308 newly diagnosed patients among which 21 were found to have metastases to bone on the basis of imaging of the entire skeleton. The AJR study protocol MRI was limited in scope and explored “most of the pelvic bone and proximal portion of the femoral head” and the lumbar spine.
The rationale for limiting the imaging to only the pelvis and lumbar spine is the many prior studies that have shown that “the possibility of isolated peripheral metastases is negligible and even distant bone metastases without pelvic and lumbar spinal involvement is unlikely.”
In the study the MRI findings were compared to the results of biopsy or surgical specimens from abnormal areas or a “comprehensive review of bone scanning, prostate MRI, CT, or a combination of these modalities, follow-up imaging studies for equivocal lesions (targeted radiology, dedicated CT or MRI and PET) and clinical follow-up … .”
“According to the reference standard [as described above] 12 of 21 patients (57.1%) had bone metastases in areas not explored with the prostate [and lumbar] MRI, that is, the cervical spine, sternum, skull, ribs, scapula, and humerus. However, “Only 1 of the 21 (4.8%) patients had bone metastases only in an area not explored with the prostate MRI, that is, the thoracic spine.”
There were 119 patients considered to be at high risk for bone metastases. In this group the sensitivity and specificity of the imaging protocol was 95% and 100%, and the positive predictive and negative predictive values were 100% and 99%, respectively.
Previous studies have reported the superiority of whole-body MRI scans and scans of the entire spine compared to bone radioisotope scanning (such as with Technetium) or a sequential work-up. However, whole-body and axial spine MRI have the disadvantage of unavailability, high cost, and scanning time. There is no reported difference between MRI and CT in establishing the size of regional lymph nodes.
The authors of the AJR article contend their protocol offers a practical technique as “one-stop-shopping” for the staging of men newly diagnosed with prostate cancer.
In Addition to Patients at High Risk Which Other Patients are Most Likely to Benefit from this Extended Protocol?
Appropriate candidates for this comprehensive approach are high-risk and high-risk intermediate-risk patients. In European Urology. 2013 Dec Zelefsky et.al. proposed a new risk classification system for the heterogeneous intermediate risk group. The high-risk group was defined as primary Gleason score 4, > 50% positive biopsy cores, and two or more of the three NCCN risk factors in the current intermediate-risk grouping. Favorable intermediate-risk was defined by a single NCCN risk factor combined with Gleason < 3 + 4, with <50% of the biopsy cores containing cancer. The Gleason score is the most consequential element in both high- and favorable-risk definitions. NCCN intermediate criteria are Clinical stage T2b or T2c, or Gleason score 7, or PSA 10 – 20 ng/mL.
The Distribution of Metastatic Spread to Bone and the Biology of Cancer Growth in Bone:
The credibility of the assessing metastases in the lumbar spine and pelvis as a surrogate for metastatic spread to the entire skeleton is based on: 1) the biologic pattern of prostate cancer migration from the prostate gland, and 2) the biology of cancer growth in the bone.
The distribution of metastatic sites has been well studied. The consensus favors dissemination, probably upward through Batson’s venous plexus from the pelvis, upward via these vertebral veins and rising sequentially through the lumbar vertebra into the higher levels of the axial skeleton, i.e. spine. Although cancer cell can spread directly from the prostate into the blood stream, spreading into the bone appears to be the preferential pattern in early dissemination.
Wang C, et al., Nuclear Medicine Communications. 2012, in “Studies on the distribution features of bone metastases in prostate cancer,” found that in the presence of widespread skeletal metastases, 99% (903/912) also occurred associated with sites in the pelvis and vertebra.” “In [instances of] fewer bone metastases, the proportion of metastatic lesions in the lumbar vertebra was the highest … . Accordingly, tumor lesions frequently encroached on the lumbar vertebra at first; the lumbar vertebrae were the most important predilection site in early bone metastases.”
Similar data in support of the preferential metastatic spread to pelvis and lower spine was expressed by Larbi et. al. in “Whole Body MRI (WB-MRI) Assessment of Metastatic Spread in Prostate Cancer: Therapeutic Perspective on Targeted Management of Oligometastatic Disease,” The Prostate, 2016. [oligo = few; i.e. 3 or fewer sites] In 96 patients “No patients were diagnosed with exclusive non-axial bone metastases in the absence of axial metastases. The three most commonly involved areas were the left ilium 38%, lumbar spine, 38.5% and thoracic spine, 35%.
These authors expressed a strong preference in imaging modality: “MRI is highly sensitive for detecting BM [bone metastases] ; its superiority over [the Technetium scan] has been repeatedly demonstrated in multiple studies and meta-analysis [six references provided].”
The biology of the growth of prostate cancer in the bone gives an advantage to MRI over the Technetium scan for early detection. After cancer cells or clusters of cells have been seduced to home to the bone marrow, the cross talk between the microenvironment and the cells promotes proliferation. It is this mass, denser than surrounding tissue, that can be detected by the MRI. Later, the proliferating cancer effects degradation of the surrounding bone matrix, a process not visualized in radiotracer scans. Later an osteoblastic response follows in an attempt to replace the lost bone, and remodeling takes place. The increased cellular activity involved in bone remodeling can now be detected by, say, a Technetium scan.
This biology is the basis of the greater sensitivity of MRI for early bone marrow metastases. This process is discussed in detail in a review in the Asian Journal of Andrology (2009) by Clark, NW, “Molecular mechanisms of metastases in prostate cancer.”
The Protocol in Greater Detail: What Does the Protocol Entail, What Does it Image, and What Study to Order:
The routine protocol used by Woo et al. includes multiparametric MRI sequences (T1, T2, diffusion weight pre-contrast; and T1-weighted gradient echo pre- and contrast-enhanced) MRI sequences targeted to the prostate and a single, non-contrast, T1-weighted sequence of the lumbar spine in the axial plane. The mpMRI prostate and lumbosacral sequences can be accomplished without moving the patient and performed in a single session.
The prostate study provides the best available imagine information about the location and size of the largest tumor mass, the “index” lesion, within the prostate and serves as a guide for a targeted re-biopsy if necessary. Properly interpreted, the mpMRI in conjunction with PIRADS ( Prostate Imaging Reporting and Data System ) classification allows assigning the index lesion a likelihood of showing cancer or biopsy — PIRADS 1, very low; to 5, very highly likely. The diffusion weighted sequence can additionally suggest a Gleason grade for the lesion.
Lumbar spinal bone marrow, virtually all pelvic marrow is imaged, and lymph nodes are included. As described by Wang et al. and as found by Woo et al, few patients with bone metastases will be missed with this as a standard protocol. Recognizing that a very small number of patients with isolated thoracic spine lesions will be missed with this protocol, a thoracic spine study can be added to capture these lesions.
BOTTOM LINE: After a biopsy diagnosis of high-tier intermediate-risk or high-risk prostate cancer, staging of the disease can be accurately gained with a multiparametric MRI of the prostate and pelvis supplemented with a limited MRI of the lumbar spine.