Capromab Pendetide

A review.Imaging is often used to evaluate men with biochem. recurrence (BCR) of prostate cancer after definitive primary treatment (radical prostatectomy [RP] or radiotherapy [RT]).The goal of imaging is to identify the source of elevated or rising serum prostate-specific antigen (PSA) levels because subsequent management depends on disease location and extent.Salvage therapy (with surgery or radiation) may be considered for select cases with BCR to provide addnl. potential opportunity for cure.The salvage treatment strategy may be extended to regional adenopathy.Patients with limited distant metastases on imaging, referred to as oligometastatic disease (≤5 demonstrable lesions), may be candidates for close observation, systemic hormonal therapy, or metastases-directed therapies with or without local therapy, depending on sites of recurrence.Patients with metastatic disease are typically treated with systemic therapy.The purpose of this document is to describe the appropriate use of imaging in the diagnostic evaluation of patients with BCR after definitive primary treatment.The imaging modalities that were considered included CT, bone scan, and the U.S.Food and Drug Administration (FDA)-approved PET radiotracers that track malignancy-induced lipogenesis (¹¹C-choline) and amino acid metabolism (¹⁸F-fluciclovine).The prostate-specific membrane antigen (PSMA)-targeted monoclonal antibody, ¹¹¹In-capromab pendetide, is also included for historical perspective because it is neither available nor used clin.The new class of PSMA-targeted PET radiotracers have generated considerable interest and are discussed briefly, although these agents are currently not approved for routine clin. use in the United States.Moreover, whole-body MRI (WB-MRI), with or without diffusion-weighted imaging, is excluded.Although WB-MRI may have utility in this clin. setting, particularly for the detection of bone metastases, the variability in availability, accessibility, quality, and standardization, as well as the fact that there are no currently established procedural terminol. codes for reimbursement, has hindered its clin. adoption (1,2).Representatives from the Society of Nuclear Medicine and Mol. Imaging (SNMMI), the European Association of Nuclear Medicine (EANM), the American Society of Clin. Oncol. (ASCO), the American College of Nuclear Medicine (ACNM), the American Society for Radiation Oncol. (ASTRO), the American Urol. Association (AUA), the American College of Physicians (ACP), the American College of Radiol. (ACR), and the World Mol. Imaging Society (WMIS) assembled under the auspices of an autonomous workgroup to develop the following appropriate use criteria (AUC).This process was performed in accordance with the Protecting Access to Medicare Act of 2014 (3).This legislation requires that all referring physicians consult AUC by using a clin. decision support mechanism before ordering advanced diagnostic imaging services.These services include diagnostic MRI, CT, and nuclear medicine procedures such as PET, among other services specified by the Secretary of Health and Human Services in consultation with physician specialty organizations and other stakeholders.The AUC herein are intended to aid referring medical practitioners in the appropriate use of imaging for the diagnostic evaluation of patients with BCR of prostate cancer after definitive primary treatment.Prostate cancer is the second most commonly diagnosed cancer worldwide (13.5% of cancer diagnoses in men; 1,276,106 cases in 2018) and the fifth most common cause of cancer-related mortality among males (6.7%; 358,989 deaths in 2018) (4).In the United States, prostate cancer is the most commonly diagnosed nonskin cancer in men (a projected 19% of all new cases of cancer; 164,690 cases in 2018) and the second most common cause of cancer-related mortality (a projected 29,430 deaths in 2018) (5).Despite local definitive therapy, up to 40% of patients will develop recurrent disease (6).Most of these patients will have BCR with no evidence of metastasis on the basis of widely used standard imaging techniques (contrast-enhanced abdomen and pelvis CT, WB 99mTc-based bone scan, or pelvis multiparametric MRI), and the disease will manifest only with elevated serum PSA levels.The definition of BCR (also referred to as PSA relapse) depends on the type of prior definitive therapy.In patients who have undergone RP, the AUA defines BCR when the serum PSA level is ≥ 0.2 ng/mL, measured 6-13 wk after surgery, and confirmed by a second determination of a PSA level of > 0.2 ng/mL (7).In patients treated with RT, the ASTRO Phoenix Criteria defines BCR as a rise in PSA level of 2 ng/mL or more above the nadir regardless of androgen deprivation therapy (ADT) (8).The significance of biochem. recurrent disease varies considerably according to individual risk factors.One clin. important prognostic variable is PSA doubling time.For instance, prostate cancer-specific survival is approx. 90% in patients with a PSA doubling time of ≥ 15 mo (highest quartile), whereas it is about 20% for patients with a PSA doubling time of < 3 mo (lowest quartile) (9).In part because of this wide variability in disease aggressiveness, coupled with competing causes of mortality and the typically long time to documented metastatic disease by standard imaging (median metastasis-free survival is 10 y in patients with BCR and no treatment), there is no defined standard management for this patient population (10).The development of metastasis in a patient signals that a change in treatment approach is warranted.Since the 1940s, the foundation of treatment for metastatic prostate cancer has been testosterone-lowering therapy.It is likely that the use of more sensitive imaging techniques will identify patients earlier who are at higher risk of developing overt metastases identified by more commonly used techniques.In some scenarios, earlier intervention in the disease process may result in improved outcomes for patients, as has been seen with postoperative RT (11).RT after a prostatectomy is commonly used to eradicate microscopic residual disease in the prostate bed, thereby reducing the risk of recurrence.Defining who needs postoperative RT is most often based on surgical pathol. and postoperative PSA because standard imaging does not have sufficient sensitivity to identify early recurrences in the PSA range where salvage treatment is more likely to be curative.There is growing evidence that genomic biomarkers (e.g., Decipher, GenomeDx Biosciences, San Diego, CA) can have utility in this clin. setting, although it remains unclear as to how this information affects imaging choice (12,13).In the adjuvant setting, pathol. (pT3a/b or surgical margins pos. for disease) currently drives the addition of RT.In the salvage setting, when men have persistently detectable PSA (PSA persistence) or a delayed rise in PSA level (≥0.2 ng/mL), conventional imaging does not have sufficient sensitivity to identify early recurrences.The ability to detect residual or recurrent disease within the pelvis can affect RT dose and target.In the absence of mol. imaging, the question of whether to include pelvic lymph nodes in the RT field in patients with pathol. node-neg. disease is a question that has been studied by the Radiation Therapy Oncol. Group (RTOG) 0534 trial and is awaiting final results.The first report from RTOG 0534 (3-arm randomized trial) shows gains in freedom from progression with the addition of short-term (4-6 mo) ADT to prostate bed radiation and further gains with the inclusion of pelvic lymph node RT and short-term ADT over a PSA level of 0.34 ng/mL (14).With the ability to visualize prostate cancer cells, mol. imaging can help define RT treatment fields.Similarly, mol. imaging can identify patients who have early metastatic disease and could avoid RT to the prostate fossa.The use of mol. imaging to identify oligometastatic prostate cancer has allowed for addnl. treatment strategies in patient care (15).Studies show a benefit (e.g., biochem. progression-free survival, distant progression-free survival) to metastasis-directed stereotactic body RT in the setting of oligometastatic prostate cancer (16-18).Mol. imaging can enhance the postoperative treatment algorithm for prostate cancer patients by identifying targets for RT.This document is the product of an extensive literature search in combination with expert opinion.Its intent is to provide up-to-date information and recommendations for AUC for approved (in the United States) imaging technologies in the setting of BCR of prostate cancer after definitive treatment.We also discuss the outlook for upcoming imaging technologies that are anticipated to be approved in the United States relatively soon.