Reasons for Discordance between 68Ga-PSMA-PET and Magnetic Resonance Imaging in Men with Metastatic Prostate Cancer.

BACKGROUND: PSMA PET has emerged as a "gold standard" imaging modality for assessing prostate cancer metastases. However, it is not universally available, and this limits its impact. In contrast, whole-body MRI is much more widely available but misses more lesions. This study aims to improve the interpretation of whole-body MRI by comparing false negative scans retrospectively to PSMA PET. METHODS: This study was a retrospective sub-analysis of a prospectively collected database of patients who participated in a clinical trial of PSMA PET/MRI comparing PSMA PET and whole-body MRI from 2018-2021. Subjects whose separately read PSMA PET and MRI diagnostic reports showed discrepancies ("false negative" MRI cases) were selected for sub-analysis. The cases were reviewed by the same attending radiologist who originally read the scans. The radiologist noted specific features on MRI indicating metastatic disease that were initially missed. RESULTS: Of 263 cases, 38 (14%) met the inclusion criteria and were reviewed. Six classes of mpMRI false negatives were identified: anatomically normal (18, 47%), atypical MRI appearance (6, 16%), mischaracterization (1, 3%), undercall (6, 16%), obscured (4, 11%), and no abnormality on MRI (3, 8%). Considering that the atypical and undercalled cases could have been adjusted in retrospect, and that 4 additional cases had positive lesions to the same extent and 11 further cases had disease confined to the pelvis, only 11 (4%) of the original 263 would have had disease outside of a conventional radiation treatment plan. CONCLUSION: Notably, almost 50% of the cases, including most lymph node metastases, were anatomically normal using standard criteria. This suggests that current anatomic criteria for evaluating prostate cancer lymph node metastases are not ideal, and there is a need for improved criteria. In addition, 32% of cases involved some element of human interpretive error, and, therefore, improving reader training may lead to more accurate results.

Failure Patterns by PSMA PET for Recurrent Prostate Cancer after Prostatectomy and Salvage Radiation.

OBJECTIVE: To characterize patterns of failure using prostate-specific membrane antigen positron emission tomography (PSMA PET) after radical prostatectomy (RP) and salvage radiotherapy (SRT). METHODS: Patients with rising PSA post-RP+SRT underwent 68Ga-HBED-iPSMA PET/CT on a single-arm, prospective imaging trial (NCT03204123). Scans were centrally reviewed with pattern-of-failure analysis by involved site. Positive scans were classified using 3 failure categories: pelvic nodal, extra-pelvic nodal or distant non-nodal. Associations with failure categories were analyzed using cumulative incidence and generalized logits regression. RESULTS: We included 133 men who received SRT a median of 20 months post-RP; 56% received SRT to the prostatic fossa alone, while 44% received pelvic SRT. PSMA PET/CT was performed a median of 48 months post-SRT. Overall, 31% of PSMA PET/CT scans were negative, 2% equivocal and 67% had at least 1 positive site. Scan detection was significantly associated with PSA level prior to PSMA PET/CT. Analysis of 89 positive scans demonstrated pelvic nodal (53%) was the most common relapse and fossa relapse was low (9%). Overall, positive scans were pelvic (n = 35, 26%), extra-pelvic nodal (n = 26, 20%) or distant non-nodal failure (n = 28, 21%), and 70% of positive scans were oligorecurrent. We observed similar cumulative incidence for all failure categories and relatively few clinicodemographic associations. Men treated with pelvic SRT had reduced odds of pelvic failure versus exclusive fossa treatment. CONCLUSION: Pelvic, extra-pelvic nodal, and distant non-nodal failures occur with similar incidence post-SRT. Regional nodal relapse is relatively common, especially with fossa-only SRT. A high oligorecurrence rate suggests a potentially important role for PSMA-guided focal therapies.

68Ga-PSMA-HBED-CC PET/MRI is superior to multiparametric magnetic resonance imaging in men with biochemical recurrent prostate cancer: A prospective single-institutional study.

BACKGROUND: The primary objective was to compare the overall diagnostic performance, presented as detection rate of 68Ga-PSMA-HBED-CC positron emission tomography/magnetic resonance imaging (PSMA PET/MRI) versus conventional, multiparametric MRI (mpMRI) in a population of patients with biochemically recurrent prostate cancer. In conjunction with this analysis, secondary objectives included the evaluation of the detection rate stratified by PSA levels and primary treatment modality. METHODS: A total of 165 PSMA PET MRI were performed from April 2018 to May 2021, of whom 108 were presenting for biochemical recurrent disease. The PSMA PET vertex to thigh were read by two different board-certified nuclear medicine physicians while the MRI head and neck, chest, abdomen, and pelvis (with dedicated, PI-RADS compliant multiparametric prostate MRI) were read by two board certified diagnostic radiologists. ANALYSIS: PSMA PET/MRI had a higher detection rate than mpMRI when evaluating patients with biochemical recurrence (BCR) with similar results demonstrated when sub-analysis was performed using PSA levels, primary treatment modality, and time since androgen deprivation therapy. Our study also showed PSMA PET/MRI had a higher sensitivity than mpMRI. DISCUSSION: Our findings demonstrate that PSMA PET/MRI is a better imaging modality in the detection of disease in the setting of BCR when compared to MRI alone. Combined utility with PSMA PET/MRI is a powerful tool which can aid in not only the detection of disease, but also guide in treatment planning for prostate cancer patients.

Review of commonly used prostate specific PET tracers used in prostate cancer imaging in current clinical practice.

18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) underperforms in detecting prostate cancer (PCa) due to inherent characteristics of primary and metastatic tumors, including relatively low rate of glucose utilization. Consequently, alternate PCa PET imaging agents targeting other aspects of PCa cell biology have been developed for clinical practice. The most common dedicated PET imaging tracers include 68Ga/18F prostate-specific membrane antigen (PSMA), 11C-Choline, and 18F-fluciclovine (Axumin™). This review will describe how these agents target specific inherent characteristics of PCa and explore the current literature for these agents for both primary and recurrent PCa, comparing the advantages and limitations of each tracer. Both 11C-Choline and 18F-Fluciclovine PET have been shown to detect nodal and osseous disease at higher rates compared to FDG-PET but offer no additional benefit in detecting prostate disease, especially in primary staging. As a result, PSMA PET, specifically 68Ga-PSMA-11, has emerged as a key imaging option for both primary and recurrent cancer. PSMA PET may be more sensitive than MRI at the local level and more sensitive than 11C-Choline and 18F-Fluciclovine PET for distant disease. Furthermore, compared to 11C-Choline and 18F-Fluciclovine PET, 68Ga-PSMA-11 PET has higher detection rates at low PSA levels (<2 ng/dL). With improved delineation of disease, PSMA imaging has influenced treatment planning; radiation fields can be narrowed, and patients with isolated or oligo-metastatic disease can be spared systemic therapy. The retrospective nature of many of the studies describing these PCa imaging modalities complicates their assessment and comparison.

Lung cancer screening in patients with previous malignancy: Is this cohort at increased risk for malignancy?

OBJECTIVES: To determine the rate of second primary lung cancer (SPLC) and describe the clinical characteristics and radiological findings in individuals with a prior history of cancer presenting to a low-dose computed tomography (LDCT) lung cancer screening program at a tertiary cancer center. METHODS: Patients with a previous history of malignancy, a life expectancy ≥ 5 years referred for CT lung cancer screening between May 2, 2011, and November 28, 2018, were included. Demographics regarding risk factors including smoking history and prior history of thoracic radiation were collected. CT scan features assessed nodule size, morphologic features, and number. The Lung-CT Reporting and Data System (Lung-RADS) scoring system was retrospectively applied to studies performed before October 2014 and prospectively applied to remainder of studies. Data was collected in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner. RESULTS: A total of 543 patients were studied (mean age of 66 years). All had a previous history of cancer, most commonly breast cancer 205 (38%), head and neck cancer 105 (19%), and lung cancer 87 (16%). Of screening CTs performed, 17.5% were positive screening study results as per Lung-RADS scoring system. SPLC was diagnosed in 35 patients (6.4%) with 21 prevalence cancers detected and 14 interval cancers detected in subsequent screening rounds. CONCLUSIONS: The rate of screen-detected SPLC in patients with prior malignancy is higher than reported rates seen in historical prospective screening studies. Our study suggests the need for prospective research to evaluate any mortality benefit that screening may have in this population. KEY POINTS: • The rate of screen-detected second primary lung cancer in patients with prior malignancy is higher than reported rates seen in historical prospective randomized lung cancer screening studies in a general screened population. • Patients with a prior malignancy undergoing lung cancer screening have higher rates of positive screening studies and higher rates of invasive diagnostic procedures than those reported in a general screening population. • Prospective research is required to evaluate if screening offers a mortality benefit in this population.

The Role of Theranostics in Prostate Cancer.

Theranostics in men with metastatic castration-resistant prostate cancer (mCRPC) has been developed to target bone and the tumor itself. Currently, bone-directed targeted alpha therapy with radium-223 (223Ra) is the only theranostic agent proven to prolong survival in men with mCRPC who have symptomatic bone metastases and no known visceral metastases. The clinical utility and therapeutic success of 223Ra has encouraged the development of other tumor-targeting theranostic agents in mCRPC, primarily targeting prostate-specific membrane antigen (PSMA) with radioligand therapy (RLT). There is increasing evidence of promising response rates and a low toxicity profile with 177Lu-labeled PSMA RLT in patients with mCRPC. A phase III randomized study of 177Lu-labeled PSMA RLT has completed accrual and is awaiting results as to whether the drug improves radiographic progression-free survival and overall survival in men with mCRPC receiving standard of care treatments. Additional early clinical trials are investigating the role of tumor-directed targeted alpha therapy with radiotracers such as 225Ac. In this article, we review the current status of theranostics in prostate cancer, discussing the challenges and opportunities of combination therapies with more conventional agents such as androgen receptor inhibitors, cytotoxic chemotherapy, and immunotherapy.

Imaging of Novel Oncologic Treatments in Lung Cancer Part 1: Systemic Therapies.

Thoracic tumors are a leading cause of cancer-related morbidity and mortality. In recent years, developments in oncologic treatments for these tumors have ushered in an era of targeted therapy, and, in many cases, these novel treatments have replaced conventional strategies to become standard therapeutic options, particularly in those with lung cancer. Targeted medical therapies for lung cancer now include angiogenesis inhibitors, tyrosine kinase inhibitors, and immunotherapeutic agents. Several novel ablative therapies have also gained widespread acceptance as alternatives to conventional surgical options in appropriately selected patients. Tumors treated with targeted medical therapies can respond to treatment differently when compared with conventional therapies. For example, pseudoprogression is a well-described phenomenon in patients receiving checkpoint inhibitor immunotherapy in which an initial increase in tumor burden is followed by a decrease in tumor burden and sometimes partial or complete response, while the frequent cavitating responses seen when antiangiogenic agents are used can be difficult to quantify using existing response assessment criteria. In some cases, novel response assessment criteria are needed to adequately capture response. In addition, numerous treatment-related side effects have been described, which are important to recognize, both to ensure appropriate treatment and to avoid misclassification as worsening tumor. Imaging plays a vital role in the assessment of patients receiving targeted medical therapy, and it is essential that thoracic radiologists are familiar with the rationale underpinning these treatments and the expected posttherapy findings.

Imaging of Novel Oncologic Treatments in Lung Cancer Part 2: Local Ablative Therapies.

Conventional approaches to the treatment of early-stage lung cancer have focused on the use of surgical methods to remove the tumor. Recent progress in radiation therapy techniques and in the field of interventional oncology has seen the development of several novel ablative therapies that have gained widespread acceptance as alternatives to conventional surgical options in appropriately selected patients. Local control rates with stereotactic body radiation therapy for early-stage lung cancer now approach those of surgical resection, while percutaneous ablation is in widespread use for the treatment of lung cancer and oligometastatic disease for selected other malignancies. Tumors treated with targeted medical and ablative therapies can respond to treatment differently when compared with conventional therapies. For example, after stereotactic body radiation therapy, radiologic patterns of posttreatment change can mimic disease progression, and, following percutaneous ablation, the expected initial increase in the size of a treated lesion limits the utility of conventional size-based response assessment criteria. In addition, numerous treatment-related side effects have been described that are important to recognize, both to ensure appropriate treatment and to avoid misclassification as worsening tumor. Imaging plays a vital role in the assessment of patients receiving targeted ablative therapy, and it is essential that thoracic radiologists become familiar with these findings.

Deficiencies in patients' comprehension of implantable cardioverter defibrillator therapy.

BACKGROUND: Patients receive education before implantable cardioverter defibrillator (ICD) implantation. Patients' understanding of ICD therapy requires investigation. METHODS: A retrospective cohort study was carried out at two implant centers where patients are educated during a consenting process pre-ICD implantation. Questionnaires examining understanding of ICD therapy were completed during telephone interviews of patients with ICDs. RESULTS: Of 75 patients interviewed, 62 (83%) were male. The median age at time of ICD implantation was 64 years (standard deviation [SD] = 9.4; range: 29-82 years). The median interval from implantation to interview was 3 years (SD = 1.9; range: 0.1-9.0 years). Despite 83% (62 of 75) claiming to understand the reason for ICD implantation, no patient suggested arrhythmia termination when describing the indication. Of shock recipients, 60% (12 of 20) felt poorly prepared for shock therapy. Of patients who experienced a device-related complication, 83% (10 of 12) reported feeling inadequately forewarned of complications. Excluding patients with cardiac resynchronization therapy defibrillators (n = 6), 65% (45 of 69), 52% (36 of 69), 50% (35 of 69), and 61% (42 of 69) believe their ICD reduces risk of heart attack and improves breathing, exercise capacity, and heart function, respectively. Ninety-three percent (70 of 75) are satisfied with their decision to accept ICD therapy. Only 12% (9 of 75) believe they will want to inactivate therapies in setting of terminal illness. CONCLUSIONS: Despite preimplantation education, patient comprehension of the risks and benefits of ICD therapy is poor. Patients' expectations of ICD therapy may be inappropriate. Education strategies before and after implantation require improvement.