Lutetium 177 (177Lu)-PSMA therapy is increasingly being adopted for patients with metastatic prostate cancer. Although therapy results have been encouraging, there is still room for optimization, particularly regarding tracer uptake and absorbed dose to the salivary glands. The concept of using a small molecular weight albumin-binding entity attached to the PSMA ligand to enhance the blood-circulation time was the basis for development of 177Lu-PSMA-ALB-56[a], which is a PSMA radioligand with higher tumor accumulation compared to other established PSMA ligands with relatively low background retention. Ten patients with metastatic castration resistant prostate cancer (mCRPC) were treated with a single dose of approximately 3.3 GBq (89.1 mCi) of 177Lu-PSMA-ALB-56 followed by sequential quantitative SPECT/CT acquisition at 1.5 hours, 6 hours, 24 hours, and 48 hours as well as 7 days following therapy administration in order to calculate tracer time activity curves (TACs) for tumor and critical organs for dosimetry evaluation. Quantitative SPECT/CT-based dosimetry for 3 such patients is highlighted in this clinical case review.
Quantitative SPECT/CT is key to obtaining accurate TACs for subsequent dosimetry. Symbia SPECT/CT enabled multibed SPECT/CT acquisitions with accurate CT attenuation correction and scatter correction along with collimator detector response modeling to obtain SPECT/CT data that could be used to obtain quantitative information on tracer concentration in Bq/ml. Quantitative multibed WB SPECT/CT data could be used in commercially available dosimetry software for accurate absorbed dose calculation. Considering the higher tumor absorbed dose possibility with 177Lu PSMA-ALB-56, there is potential of improving radionuclide therapy of metastatic prostate cancer using such radioligands, although higher renal and salivary dose considerations need to be considered. In such situations, accurate dosimetry using sequential SPECT/CT is of key importance for improving therapeutic outcomes while avoiding toxicity.
One additional lesion unseen on single-bed SPECT/CT was classified as equivocal on double-bed SPECT/CT acquisition. It induced a change in conclusion diagnostic in one patient with prostate cancer (1%) from benign to equivocal. WBS was interpreted as equivocal, with 2 equivocal lesions on the ribs. Based on single-bed SPECT/CT on the thorax, the 2 lesions on the ribs were re-classified as benign. On the double-bed SPECT/CT, 1 equivocal lesion was found in the iliac bone on the scan inducing an equivocal diagnostic conclusion. A guided biopsy of the equivocal lesion did not show malignancy (See Fig. 2). No patient had a change of diagnostic conclusion to suspicious for malignancy on double-bed SPECT/CT.
The management of advanced prostate cancer is rapidly evolving. Clinicians are challenged to remain up-to-date and informed with respect to a multitude of treatment options for patients with advanced prostate cancer. To assist in clinical decision-making, evidence-based guideline statements were developed to provide a rational basis for evidence-based treatment. This guideline covers advanced prostate cancer, including disease stages that range from prostate-specific antigen (PSA) recurrence after exhaustion of local treatment options to widespread metastatic disease.
1. In patients with suspicion of advanced prostate cancer and no prior histologic confirmation, clinicians should obtain tissue diagnosis from the primary tumor or site of metastases when clinically feasible. (Clinical Principle)
2. Clinicians should discuss treatment options with advanced prostate cancer patients based on life expectancy, comorbidities, preferences, and tumor characteristics. Patient care should incorporate a multidisciplinary approach when available. (Clinical Principle)
3. Clinicians should optimize pain control or other symptom support in advanced prostate cancer patients and encourage engagement with professional or community-based resources, including patient advocacy groups. (Clinical Principle)
16. In selected mHSPC patients with low-volume metastatic disease, clinicians may offer primary radiotherapy to the prostate in combination with ADT. (Conditional Recommendation; Evidence Level: Grade C)
36. Clinicians should recommend preventative treatment for fractures and skeletal-related events, including supplemental calcium, vitamin D, smoking cessation, and weight-bearing exercise, to advanced prostate cancer patients on ADT. (Clinical Principle)
37. In advanced prostate cancer patients at high fracture risk due to bone loss, clinicians should recommend preventative treatments with bisphosphonates or denosumab and referral to physicians who have familiarity with the management of osteoporosis when appropriate. (Clinical Principle)
The methodology team developed criteria for inclusion and exclusion of studies based on the Key Questions and the populations, interventions, comparators, outcomes, and settings (PICOTS) of interest. The population was patients with advanced prostate cancer as described in Table 3. Treatments included first and second line antiandrogens, immunotherapy, chemotherapy, radiation therapy, surgery, radiopharmaceuticals, and surveillance strategies. Comparisons were against placebo, no therapy, or another active intervention; and intermittent versus continuous therapy. Outcomes included overall survival (OS), prostate cancer mortality, progression-free survival (PFS), prostate-specific antigen progression-free survival (PSA-PFS), failure-free survival, metastases-free survival, time to metastases, time to progression, skeletal events, and adverse events.
An integral part of the guideline development process at the AUA is external peer review. The AUA conducted a thorough peer review process to ensure that the document was reviewed by experts in the diagnosis and management of Advanced Prostate Cancer. In addition to reviewers from the AUA PGC, Science and Quality Council (SQC), and Board of Directors (BOD), the document was reviewed by representatives from ASTRO, SUO, and ASCO as well as external content experts. Additionally, a call for reviewers was placed on the AUA website from December 2-16, 2019 to allow any additional interested parties to request a copy of the document for review. The guideline was also sent to the Urology Care Foundation and representation from prostate cancer advocacy to open the document further to the patient perspective. The draft guideline document was distributed to 96 peer reviewers. All peer review comments were blinded and sent to the Panel for review. In total, 44 reviewers provided comments, including 34 external reviewers. At the end of the peer review process, a total of 522 comments were received. Following comment discussion, the Panel revised the draft as needed. Once finalized, the guideline was submitted for approval to the AUA PGC, SQC, and BOD as well as the governing bodies of ASTRO and SUO for final approval.
Prostate cancer is the most commonly diagnosed solid organ malignancy for men in the U.S. and remains the second leading cause of cancer deaths for this population. Approximately 175,000 new diagnoses of prostate cancer and over 31,000 deaths were estimated in the U.S. in 2019. 6 Importantly, the incidence of metastatic hormone-sensitive prostate cancer (mHSPC) has been increasing in recent years, and recent improvements in survival through combination therapies have resulted in a renaissance in the entire landscape for clinicians caring for men with advanced metastatic prostate cancer. Prostate cancer deaths are typically the result of progression to metastatic castration-resistant prostate cancer (mCRPC). Historically, the median survival for men with mCRPC was less than two years, but due to several factors including the impact of novel therapies, the median survival is now increasing with some men surviving beyond five years. 7 Furthermore, therapeutic advances in the treatment landscape for mHSPC and mCRPC render treatment decisions and sequencing increasingly complex. It is against this backdrop that the Panel provides evidence-based guidance for treatment of advanced prostate cancer and looks to the future with cautious optimism.
Clinicians treating men with advanced prostate cancer are challenged with the rapidly evolving prostate cancer landscape given the approval of new classes of agents for use in various prostate cancer disease states. The increasing complexity of advanced prostate cancer management underscores the need for the current clinical practice guideline, developed to provide a rational basis for treatment of patients with advanced disease, based on currently available published data. To assist in clinical decision-making, guideline recommendations are furnished according to disease state across the entire continuum of advanced prostate cancer.
This guideline covers advanced prostate cancer as defined by the five disease states outlined below. It should be noted that this guideline does not cover local therapy (see AUA Guideline on Clinically Localized Prostate Cancer). 8 The patient population covered in this guideline is assumed to have already received local or pelvic therapy, including adjuvant and salvage therapy (i.e., exhaustion of local treatment options). Further, neuroendocrine tumors and small cell variants were considered outside the scope of this guideline.
After local therapy including surgery or radiation, the first sign of recurrence is typically a rising PSA in the absence of visible metastases. This is assuming also that all forms of local therapy (e.g., salvage radiotherapy after radical prostatectomy, or salvage prostatectomy/salvage local ablative therapy after external beam radiotherapy [EBRT]) have been exhausted. Patients understand that their local treatment has not eradicated the cancer because of continued rises in PSA. Management of this disease state is controversial as evidence for optimal treatment approaches is lacking. 59ce067264