Imaging in the detection of advanced disease

Pre-treatment detection of metastases

The technetium bone scan is a widely available and sensitive method for diagnosing the initial spread of cancer to bone,  particularly for osteoblastic metastases.

However,  it should be reserved for symptomatic patients and for those with high-risk disease, as the incidence of bone metastasis in men with clinically localized prostate cancer at diagnosis is low. The National Comprehensive Cancer Network (NCCN) recommends bone scans for asymptomatic patients with a life expectancy greater than 5 years only if the PSA is above 20 ng/ml, the Gleason score is at least 8, or the clinical stage is T3 or T4 [48]. The American College of Radiology recommends bone scans for patients with a PSA above 10 ng/ml [49] and a Gleason score greater than 6 (the same threshold used at our institution).

In prostate cancer, lymph node metastasis is even less common than bone metastasis. The NCCN guidelines recommend using CT or MRI only in patients with a nomogram-indicated probability of lymph node metastasis greater than 20%. As noted earlier, CT and MRI both have limited accuracy in the detection of lymph node metastases, but MRI does have the advantage of allowing the prostate and the pelvic lymph nodes to be assessed in a single examination.

Recent studies have demonstrated that MRI after administration of ultrasmall superparamagnetic iron oxide (USPIO) particles has high sensitivity and specificity (both above 90%) in the detection of prostate cancer lymph node metastases; it allows the identification of small metastatic lymph nodes (<5 mm), as well as the differentiation between benign reactive and malignant enlarged nodes [50, 51, 52].

Although this technique is extremely promising, it has not yet received regulatory approval in the United States. Furthermore, it is somewhat cumbersome, requiring contrast to be administered to the patient the day before imaging. Therefore, it has been suggested that standard MRI,  in conjunction with the standard staging nomogram, could be used to determine whether imaging with USPIO particles is warranted [41].

Post-treatment detection of metastases
When recurrence is suspected, imaging plays an essential role in evaluating a patient for metastatic disease. With a rising PSA, the first investigation ordered to search for metastases is a bone scan. However, the bone scan is rarely positive until PSA values are high, around 30 ng/ml [53]. Recently, a highly discriminating nomogram was developed for predicting the probability of a positive bone scan after biochemical failure and before the initiation of hormone therapy. The nomogram, which is based on commonly available data (including pathologic findings from the analysis of the surgical specimen and post-operative PSA data), predicted bone scan results with a concordance index of 0.93. Although the nomogram does not apply to patients treated with hormone therapy, it may prove useful for selecting patients according to their risk for a positive bone scan and reducing the total number of scans ordered [54].

If bone scan findings are indeterminate, further imaging may allow clarification.

Some studies have suggested that in cases where bone scan findings are questionable, MRI should be used as a supplementary form of imaging [55, 56]. Bone marrow MRI has been shown to be more sensitive and specific than bone scanning for the detection of bone metastases and to reveal them at an earlier stage [57]. In a recent study of 66 patients with high-risk prostate cancer, the sensitivity and specificity of one-step MRI of the axial skeleton (100% and 88%, respectively) were markedly higher than those of bone scanning (46% and 32%, respectively) for detecting bone metastases, and this changed treatment planning in a substantial proportion (22%) of patients [58]. Further research is needed to determine the diagnostic value and cost-effectiveness of one-step MRI relative to other modern imaging modalities in the assessment of bone metastases.

In patients with aggressive disease, 18 F-2-fluoro-d-deoxyglucose (18 F-FDG) PET/CT may allow precise localization of bone metastases, facilitating new treatment options such as bony ablation [59].

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