Date Published: October 16, 2012
Publisher: Hindawi Publishing Corporation
Author(s): Bertrand Tombal, Frederic Lecouvet.
Prostate cancer cells have an exquisite tropism for bone, which clinically translates into the highest rate of bone metastases amongst male cancers. Although in the latest years there has been an active development of new “bone targeted” therapies, modern diagnostic techniques for bone metastases still relies mostly on 99mTc bone scanning (BS) and plain X-ray. BS dramatically lacks specificity and sensitivity. Recent publications using modern imaging technologies have clearly pinpointed that BS grossly underestimates the true prevalence of bone metastasis. In addition BS does not allow tumour measurement and is, therefore, not appropriate to monitor response to therapy. This might be extremely important in patients harbouring high-risk localized disease that are eventually candidate for local therapy. Here we reviewed what are the emerging imaging strategies that are likely to supplant BS and to what extent they can be used in the clinic already.
In men over the age of 50, prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of death by cancer . With the intense use of PSA testing, most PCa are diagnosed at an early stage, and most are candidate to intent-to-cure therapies such as radical prostatectomy, external beam radiation therapy, or seeds implant. Initially essentially intended for low- or intermediate-risk disease, local therapies are now more often indicated in patients with high-risk localized disease and locally advanced disease. Indeed, hormone therapy has failed to demonstrate to increase overall survival when it was not associated with a local treatment . In that high-risk population; however, it is critical to precisely rule out the presence of metastases since as for today it still represents the tipping point for excluding local control.
Early BM detection is critical in the management of patients with high-risk PCa. Newly diagnosed patients with localized disease and no metastases may benefit from radical treatment with curative intent. In contrast, most guidelines recognize that patients with BM should be kept away from local therapy to avoid unnecessary side effects and treated with systemic therapy . With modern PSA-based diagnostic strategies, many patients are diagnosed while they are still asymptomatic. In screening trials, BMs are detected at diagnosis in less than 10% of the patients . This means that there is no need to perform an initial BS in every new patient. PSA value and Gleason’s score at diagnostic remain the strongest BM’s indicators. In a study conducted on 60 patients with newly diagnosed PCa, Rana et al. demonstrated that the positive predictive value of a PSA >100 ng/mL was 100% . Together with PSA, cT3-4 stage and a Gleason score >7 are the other predictors of BM; their positive predictive value being, respectively, 71.4% and 81% . Based on this trial and others, the EAU guidelines recommend that […] a staging bone scan may be superfluous if the serum PSA concentration is less than 20
ng/mL in asymptomatic patients with well-, or moderately differentiated tumours. In contrast, in patients with poorly differentiated tumours and locally advanced disease, a staging bone scan should be obtained irrespective of the serum PSA value […] . Briganti et al. have developed a risk stratification tool to select patients requiring initial imaging from a series of 853 consecutive patients . Their classification and regression tree (CART) stratifies patients into low risk (biopsy Gleason ≤7, cT1-3, and PSA <10 ng/mL), intermediate risk (biopsy Gleason ≤7, cT2-3, and PSA >10 ng/mL), and high risk (biopsy Gleason >7) conferring a risk of BM of 1.8%, 8.5%, and 16.4%. Briganti’s regression tree shows higher sensitivity (87.5%) compared to the EAU, AUA, and NCCN guidelines [8, 9, 16].
CT scanner imaging is central in the diagnosis of musculoskeletal disorders. In bone malignancies, it is not used as a screening test but as a second-line imaging technique to clear-up abnormal BS uptakes remaining unexplained after standard X-ray or to image suspicion of neurological disorders.
MRI is highly sensitive for detecting BM in cancer patients [25, 31, 51–53]. Its superiority over BS has been repeatedly demonstrated [54–56]. It has been used as a “gold standard” to evaluate PET for detecting BM and more recently to quantify PCa metastases and measure tumour response to therapy [30, 57]. However, the use of MRI in first line is often presented as “not feasible” putting forward its limited availability, costs, or limitations of published series validating the method .
Correct diagnosis of BM has emerged as major challenge for those who are developing new therapeutic strategies, including those who advocate aggressive local treatment of high-risk localized and locally advanced disease. Tc-99m BS may not be over, but the time when patients would be treated on suspicion rather than on robust evidences is passed. Many technologies including metabolic imaging by PET and MRI are indeed rapidly gaining interest in the everyday management of PCa patients. As it is for modern treatments, the diagnosis strategies will be multidisciplinary by nature and involve crossfertilization between nuclearists, urologists, and radiation oncologists.