Staging Prostate Cancer with 68Ga-PSMA-11 PET/CT in the Elderly: Is Preimaging Biopsy Imperative?

Although prostate-specific membrane antigen (PSMA) PET/CT has been shown valuable for staging biopsy-proven [B(+)] high-risk prostate cancer, elderly patients are occasionally referred for PSMA PET/CT without a preimaging confirming biopsy [B(-)]. The current study evaluated the rate, clinical characteristics, and PET-based stage of elderly B(-) patients and explored whether biopsy status affects therapeutic approach. Methods: One hundred consecutive patients at least 80 y old who underwent staging 68Ga-PSMA-11 PET/CT were included. For each patient, we documented whether preimaging biopsy was performed, the clinical parameters, the PET-based staging parameters, and the primary therapy received. Results: Thirty-four (34%) of the elderly patients included in the study had no preimaging biopsy. Compared with B(+) patients, B(-) patients were older (median age, 87 vs. 82 y; P < 0.01), with worse performance status (P < 0.01) and higher prostate-specific antigen (PSA) levels (median, 57 vs. 15.4 ng/mL; P < 0.01). On 68Ga-PSMA-11 PET/CT, all B(-) patients had avid disease, with trends toward higher rates of bone metastases (47.1% vs. 28.8%) and overall advanced disease (50% vs. 33.3%) than in B(+) patients. Among patients with localized (n = 36) or locally advanced (n = 25) disease, B(-) patients were less commonly referred than B(+) patients for definitive therapies (P < 0.01). However, higher age, Eastern Cooperative Oncology Group performance status, and PSA were other probable factors determining their therapeutic approach. Among 39 patients with advanced disease, 38 received hormonal therapy irrespective of their biopsy status. Among B(-) patients with advanced disease who were referred for hormonal therapy, 12 of 13 with follow-up data showed a biochemical or imaging-based response. Conclusion: Real-life experience with 68Ga-PSMA-11 PET/CT indicates that around one third of elderly patients are referred for imaging without a preimaging confirming biopsy. These patients are likely to be older, with a worse clinical status and higher PSA levels. Advanced disease might be more likely to be identified on their 68Ga-PSMA-11 PET/CT images, and if it is, their biopsy status does not preclude them from receiving hormonal therapy.

A lesson in humility: the added values of PET-MRI over PET-CT in detecting malignant hepatic lesions.

PURPOSE: The recent introduction of integrated PET-MRI systems into practice seems promising in oncologic imaging, and efforts are made to specify their added values. The current study evaluates the added values of PET-MRI over PET-CT in detecting active malignant hepatic lesions. METHODS: As part of an ongoing prospective study in our institution that assesses the added values of PET-MRI, subjects undergo PET-CT and subsequent PET-MRI after single radiotracer injection. The current study included 97 pairs of whole-body PET-CT and liver PET-MRI scans, of 61 patients (19/61 had ≥ 2 paired scans), all performed with [18F]FDG and interpreted as showing active malignant hepatic involvement. Primary malignancies were of colorectal/biliary/pancreatic/breast/other origins in 19/9/9/7/17 patients. Monitoring response to therapy was the indication in 86/97 cases. When PET-MRI detected additional malignant lesions over PET-CT, lesions size, their characteristics on PET-MRI, and the influence on the final report were recorded. RESULTS: In 37/97 (38.1%) cases, a total of 78 malignant lesions were identified on PET-MRI but not on PET-CT: 19 lesions (11 cases) were identified on PET of PET-MRI but not on PET of PET-CT; 37 lesions (14 cases) were small (≤ 0.8 cm) and identified on MRI only; 22 lesions (12 cases) were > 0.8 cm, had low/no [18F]FDG uptake, but were categorized as viable based on MRI. These 78 lesions caused major effect on final reports in 11/97 (11.3%) cases, changing reported response assessment category (10/86 cases) or defining malignant hepatic disease on staging/restaging scans (1/11 cases). CONCLUSION: PET-MRI offers several advantages over PET-CT in assessing the extent and response to therapy of malignant hepatic involvement. Additional malignant lesions detected on PET-MRI are attributed to superior PET performance (compared with PET of PET-CT), greater spatial resolution provided by MRI, and improved multi-parametric viability assessment. In around one-tenth of cases, findings identified on PET-MRI but not on PET-CT significantly change the final report's conclusion.

Staging 68 Ga-PSMA PET/CT in 963 consecutive patients with newly diagnosed prostate cancer: incidence and characterization of skeletal involvement.

PURPOSE: The aim of the study was to elaborate the incidence and type of skeletal involvement in a large cohort of patients with newly diagnosed prostate cancer (PCa) referred for Ga-68 PSMA-11 PET/CT staging in a single center. METHODS: Study cohort included 963 consecutive patients with newly diagnosed PCa referred for Ga-68 PSMA-11 PET/CT study for staging. The incidence of bone involvement, type of bone metastases, and extent of disease were determined and correlated with the ISUP Grade Group (GG) criteria and PSA levels. RESULTS: Bone metastases were found in 188 (19.5%) of 963 patients. Bone metastases were found in 10.7% of patients with PSA < 10 ng/dL and in 27.4% of patients with PSA > 10 ng/dL and in 6.1% of patients with GG ≤ 2/3 and in 8.9% of patients with GG 4/5. In 7.6% of the patients, skeletal involvement was extensive, while 11.9% of patients had oligometastatic disease. Osteoblastic type metastases were the most common type of bone metastases presented in 133 of the patients with malignant bone involvement (70.7%). More than half of them had only osteoblastic lesions (72 patients (38.3%)), while the other (61 patients (32.5%)) had also intramedullary and/or osteolytic type lesions. Intramedullary metastases were found in 97 patients (51.6%), while 41 (21.8%) of them were only intramedullary lesions. Osteolytic metastases were detected in 36 patients (19.2%), of which 8 were only osteolytic lesions. CONCLUSION: Although traditionally bone metastases of PCa are considered osteoblastic, osteolytic and intramedullary metastases are common, as identified on PET with labeled PSMA. Skeletal spread may be present also in patients with GG ≤ 2/3 and PSA < 10 ng/dL.

Head-to-head comparison of [68Ga]Ga-FAPI-04 and [18F]-FDG PET/CT in evaluating the extent of disease in gastric adenocarcinoma.

BACKGROUND: [18F]-Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) may sometimes be suboptimal for imaging gastric adenocarcinoma. The recently introduced [68Ga]Ga-FAPI-04 (FAPI) PET/CT targets tumor stroma and has shown considerable potential in evaluating the extent of disease in a variety of tumors. METHODS: We performed a head-to-head prospective comparison of FAPI and FDG PET/CT in the same group of 13 patients with gastric adenocarcinoma who presented for either initial staging (n = 10) or restaging (n = 3) of disease. Lesion detection and maximum standardized uptake value (SUVmax) were compared between the two types of radiotracers. RESULTS: All ten primary gastric tumors were FAPI-positive (100% detection rate), whereas only five were also FDG-positive (50%). SUVmax was not significantly different, but the tumor-to-background ratio was higher for FAPI (mean, median, and range of 4.5, 3.2, and 0.8-9.7 for FDG and 12.9, 11.9, and 2.2-23.9 for FAPI, P = 0.007). The level of detection of regional lymph node involvement was comparable. FAPI showed a superior detection rate for peritoneal carcinomatosis (100% vs. none). Two patients with widespread peritoneal carcinomatosis underwent a follow-up FAPI scan after chemotherapy: one showed partial remission and the other showed progressive disease. CONCLUSIONS: The findings of this pilot study suggest that FAPI PET/CT outperforms FDG PET/CT in detecting both primary gastric adenocarcinoma and peritoneal carcinomatosis from gastric cancer. FAPI PET/CT also shows promise for monitoring response to treatment in patients with peritoneal carcinomatosis from gastric cancer; however, larger trials are needed to validate these preliminary findings.

[STAGING CERVICAL CANCER USING PET-CT AND PET-MRI].

INTRODUCTION: Whole-body Positron Emission Tomography-Computerized Tomography (PET-CT) and pelvic Magnetic Resonance (MR) imaging are included in developed countries in the imaging algorithm of newly diagnosed cervical cancer (CC). In recent years, the novel technology of PET-MR has been introduced in the clinical practice of tumor imaging. We present a patient with newly-diagnosed CC, who was evaluated using whole-body PET-CT and pelvic PET-MR in a single visit in our department. The role of the latter technologies in defining the anatomical, metabolic and functional data for optimal staging of CC is illustrated. We review the advantages and limitations of each of the modalities in staging the primary, nodal and distant disease, discuss the importance of accurate staging for guiding clinical management, and highlight the unique benefit of PET-MR in imaging of CC.

68Ga-PSMA-11 PET/CT Follow-Up of Patients with Prostate Cancer with Bone Metastases Who Had Reduced Bone Density after Androgen Deprivation Therapy.

Bone metastases from prostate cancer (PCa) often show an increase in density on computed tomography (CT) after successful androgen deprivation therapy (ADT). Density may be reduced, however, as the disease progresses or, contrarily, when disease is no longer active. The current study investigated the role of 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) in differentiating between these two conditions. METHODS: The study cohort included 15 PCa patients with sclerotic/blastic bone metastasis in whom reduction in bone density of metastasis was noted on follow-up 68Ga-PSMA-11 PET/CT after ADT. Each patient had two PET/CT scans. Prior to the first scan, six patients were castration naïve and nine patients were already treated. All patients had ADT between the two PET/CT scans. PET parameters (SUVmax and tumor-to-background ratio), and CT parameters (HUmax) were determined and compared for each lesion on both scans. Patient's response was based on prostate-specific antigen (PSA) levels and appearance of new lesions. The Kolmogorov-Smirnov test was used to evaluate normal distribution of the continuous variables. RESULTS: Post-ADT reduction in bone density was identified in 37 lesions. The mean HUmax was 883.9 ± 175.1 on the first scan and 395.6 ± 157.1 on the second scan (p < 0.001). Twenty-one of the 37 lesions showed no increased tracer uptake on the second PET/CT scan raising the likelihood of a response. The other 16 lesions were associated with increased uptake suggestive of an active resistant disease. Bone density was not different in lesions that no longer showed an increased uptake as compared with those that did. Seven of the study patients responded to therapy, and none of the 16 lesions found in these patients showed increased 68Ga-PSMA-11 uptake. In eight patients with progressive disease, all 12 lesions in five of them showed increased 68Ga-PSMA-11 uptake, there was mixed response in two patients (having two lesions with increased uptake and one without) and although all three lesions no longer showed an increased uptake, new lesions were detected in the eighth patient. CONCLUSION: A decrease in density of bone lesions may reflect clinical progression, or contrarily, a response to therapy in patients with PCa and skeletal involvement treated with ADT. Uptake of 68Ga-PSMA-11 may separate between these two vastly opposing conditions.

Ga-PSMA PET/CT Staging of Newly Diagnosed Intermediate- and High-Risk Prostate Cancer.

BACKGROUND: Ga-prostate-specific membrane antigen positron emission tomography/computerized tomography (Ga-PSMA PET/CT) is part of the initial workup of patients with intermediate and high-risk prostate cancer provided by the Israeli national health services. OBJECTIVES: To assess the incidence of metastatic spread in consecutive patients with newly diagnosed cancer, and the potential added value of Ga-PSMA PET/CT to the staging imaging algorithm. METHODS: Patients with newly diagnosed intermediate- and high-risk prostate cancer were referred for initial staging by Ga-PSMA PET/CT between May 2016 and April 2017. Blood prostate-specific antigen (PSA) levels, clinical history, imaging reports and histopathological reports (including Gleason scores) were obtained. Maximal standardized uptake values (SUVmax) were determined for the primary lesions detected within the prostate. RESULTS: The study included 137 consecutive patients with intermediate- and high-risk disease who underwent Ga-PSMA PET/CT staging. Of these, 75 had Ga-PSMA uptake in both prostate lobes, 57 had unilateral uptake, and 5 patients had no uptake. SUVmax in the primary tumor correlated significantly with PSA levels. Thirty-five patients had increased uptake compatible with metastatic disease involving lymph nodes, bone, and viscera. Twenty-seven patients had available bone scintigraphy results: 18 (69%) of their 26 bone metastases detected by Ga-PSMA PET/CT were missed on bone scintigraphy. CONCLUSIONS: Ga-PSMA PET/CT shows promise as a sole whole-body imaging modality for assessing the presence of soft tissue and bone metastases in the setting of prostate cancer.

68Ga-PSMA is a novel PET-CT tracer for imaging of hepatocellular carcinoma: A prospective pilot study.

Background:68Ga-Prostate Specific Membrane Antigen (68Ga-PSMA), a positron emission tomography (PET) tracer that was recently introduce for imaging of prostate cancer, may accumulate in other solid tumors including Hepatocellular Carcinoma (HCC). The aim of the study was to assess the potential role of 68Ga-PSMA PET-Computed Tomography (CT) for imaging of HCC. Material and Methods: A prospective pilot study in seven patients with HCC with 41 liver lesions: 37 suspected malignant lesions (tumor lesions) and 4 regenerative nodules. For each liver lesion, uptake of 68Ga-PSMA and 18F-FDG uptake were measured [standard uptake value (SUV) and lesion-to-liver background ratios (TBR-SUV)], and correlated with dynamic characteristics (HU and TBR-HU) obtained on contrast enhanced CT data. Immunohistochemistry staining of PSMA in the tumor tissue was analyzed in samples obtained from 5 patients with HCC and compared to control samples from 3 patients with prostate cancer. Results: Thirty-six of the 37 tumor lesions and none of the regenerative nodules showed increased 68Ga-PSMA uptake while only 10 lesions were 18F-FDG avid. Based on contrast enhancement, tumor lesions were categorized into 27 homogeneously enhancing lesions, nine lesions with "mosaic" enhancement composed of enhancing and non-enhancing regions in the same lesion and a single non-enhancing lesion, the latter being the only non-68Ga-PSMA avid lesion. Using the Mann-Whitney test, 68Ga-PSMA uptake was found significantly higher in enhancing tumor areas compared to non-enhancing areas and in contrast, 18F-FDG uptake was higher in non-enhancing areas, P<0.001 for both. 68Ga-PSMA uptake (TBR SUVmax) was found to correlate with vascularity (TBR-HU) (Spearman r=0.866, p<0.001). Immunohistochemistry showed intense intra-tumoral microvessel staining for PSMA in HCC, in contrast with cytoplasmic and membranous staining, mainly in the luminal border, in prostate cancer samples. In two of the study patients 68Ga-PSMA PET-CT identified unexpected extrahepatic metastases. Four regenerative liver nodules showed no increased uptake of either of the PET tracers. Conclusion:68Ga-PSMA PET-CT is superior to 18F-FDG PET-CT in imaging patients with HCC. HCC lesions are more commonly hypervascular taking up 68Ga-PSMA in tumoral micro-vessels. 68Ga-PSMA PET-CT is a potential novel modality for imaging patients with HCC.

Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration.

The adult mouse prostate has a seemingly endless capacity for regeneration, and sonic hedgehog (SHH) signaling has been implicated in this stem cell-driven process. However, it is not clear whether SHH acts on the epithelium or stromal cells that secrete factors required for epithelial expansion. Because little is known about stromal stem cells compared with their epithelial counterparts, we used in vivo mouse genetics tools to characterize four prostate stromal subtypes and their stem cells. Using knockin reporter alleles, we uncovered that SHH signals from prostate basal epithelial cells to adjacent stromal cells. Furthermore, the SHH target gene Gli1 is preferentially expressed in subepithelial fibroblast-like cells, one of four prostate stromal subtypes and the subtype closest to the epithelial source of SHH. Using Genetic Inducible Fate Mapping to mark adult Gli1- or Smooth muscle actin-expressing cells and follow their fate during regeneration, we uncovered that Gli1-expressing cells exhibit long-term self-renewal capacity during multiple rounds of androgen-mediated regeneration after castration-induced involution, and depleted smooth muscle cells are mainly replenished by preexisting smooth muscle cells. Based on our Genetic Inducible Fate Mapping studies, we propose a model where SHH signals to multiple stromal stem cells, which are largely unipotent in vivo.

Tumor lesion detection: when is integrated positron emission tomography/computed tomography more accurate than side-by-side interpretation of positron emission tomography and computed tomography?

OBJECTIVES: To determine if there is added value to oncology studies performed with a dedicated in-line positron emission tomography (PET)/computed tomography (CT) scanner as compared with PET read side by side with diagnostic CT (DCT). METHODS: Forty-one consecutive oncology patients referred for PET/CT who had contemporary DCT scans for review were enrolled. Body regions assessed on a DCT scan were assessed on PET/CT and by side-by-side reading of PET and DCT (SBS PET/DCT). Lesions identified on DCT, the CT portion of PET/CT, SBS PET/DCT, and the reading of fused PET/CT images were scored as benign or malignant. The PET portion of the PET/CT study was read by 2 teams: the first read the SBS PET/DCT scan and the other read the complete fused PET/CT scan. For discordant lesions, the final diagnosis was determined by pathologic findings (n = 6) or imaging follow-up (n = 21). RESULTS: Twenty-seven (16.1%) of the 168 lesions were discordant when comparing analysis of fused PET/CT and SBS PET/DCT. Sixteen (9.5%) were fundamentally discordant, and 11(6.6%) were discordant in degree of confidence. For all discordant lesions only, the sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for PET/CT were 100%, 33%, 100%, 94%, and 78%, respectively, and for SBS PET/DCT, they were 38%, 50%, 19%, 73%, and 30%, respectively (P < 0.001 for sensitivity, P = not specific for specificity). The 2 main causes for misclassification on SBS PET/DCT were incorrect localization (n = 12) and changes occurring in the time gap between DCT and PET/CT (n = 4). CONCLUSIONS: In-line PET/CT offers better lesion localization in comparison to the visual fusion of PET and CT, especially for small lymph nodes, lesions adjacent to mobile organs, or lesions adjacent to the chest or abdominal wall.

Why we miss the diagnosis of appendicitis on abdominal CT: evaluation of imaging features of appendicitis incorrectly diagnosed on CT.

OBJECTIVE: Our purpose was to retrospectively evaluate the cases of patients with surgically proven appendicitis that was misdiagnosed on abdominal CT to determine the causes of the missed diagnosis. CONCLUSION: Increased awareness of the underlying factors common to most cases of the missed diagnosis of appendicitis on CT and increased radiologic vigilance in cases of atypical abdominal pain may enable us to further improve our diagnostic accuracy.

The diagnostic accuracy of 18F-fluorodeoxyglucose PET/CT in patients with gynecological malignancies.

OBJECTIVE: To evaluate the diagnostic accuracy of integrated positron emission tomography/computerized tomography (PET/CT) in patients with gynecological cancer. METHODS: Fifty-three consecutive patients with gynecologic malignancies were included. The patients were referred to our tertiary center to undergo a PET/CT scan. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PET/CT were compared with the conventional imaging assessments [CT, magnetic resonance imaging (MRI) and ultrasonography (US)]. RESULTS: All tested values were higher for PET/CT than those for the conventional modalities: sensitivity 0.97 vs. 0.40, specificity 0.94 vs. 0.65, PPV 0.97 vs. 0.70, and NPV 0.94 vs. 0.34, respectively. CONCLUSION: PET/CT is a reliable modality for assessing the extent of disease in patients with gynecologic malignancy.

Detection of recurrence in patients with rectal cancer: PET/CT after abdominoperineal or anterior resection.

PURPOSE: To assess diagnostic accuracy of combined positron emission tomography (PET) and computed tomography (CT) in detection of pelvic recurrence in patients with rectal cancer who underwent abdominoperineal or anterior resection. MATERIALS AND METHODS: Sixty-two patients were enrolled; 37 were men, and 25 were women. Seventeen patients underwent abdominoperineal resection and 45 underwent anterior resection with an anastomosis in the pelvic region before referral for PET/CT. Pelvic sites of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) uptake were rated separately on PET and PET/CT images as benign or malignant on the basis of shape, location, and intensity of (18)F FDG uptake (1-2 = benign and/or physiologic, 3 = equivocal, 4-5 = malignant). Two readers interpreted images in consensus. Altered pelvic anatomy and presence of presacral abnormalities were assessed with CT. Pelvic recurrence was confirmed with histologic analysis or clinical and imaging follow-up. Sensitivity, specificity, positive and negative predictive values, and accuracy of PET and PET/CT in the detection of pelvic recurrence were compared with lesion- and patient-based analyses by using the chi(2) test. Clinical relevance of PET/CT assessment was determined. RESULTS: Of 81 pelvic sites with increased (18)F FDG uptake, 44 were malignant. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for differentiating malignant from benign (18)F FDG uptake in the pelvis were 98%, 96%, 90%, 97%, and 93% for PET/CT and 82%, 65%, 73%, 75%, and 74% for PET, respectively. The most common cause for false-positive interpretation of PET findings was physiologic (18)F FDG uptake in displaced pelvic organs. Presacral CT abnormalities were present in 30 (48%) of 62 patients, and seven (23%) abnormalities were malignant. PET/CT was used to distinguish benign and malignant presacral abnormalities with a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 96%, 88%, and 100%, respectively. PET/CT findings were clinically relevant in 29 (47%) of 62 patients. CONCLUSION: PET/CT is an accurate technique in the detection of pelvic recurrence after surgical removal of rectal cancer.

[Left paraduodenal hernia: a report of a case and a review of clinical and diagnostic CT findings].

Internal hernias are an uncommon cause of small bowel obstruction. Paraduodenal hernias have been considered until recently the most common sub-type. Due to non-specific and intermittent signs and symptoms the diagnosis of these hernias is notoriously difficult. We report a case of a paraduodenal hernia diagnosed correctly with abdominal computed tomography that was confirmed at surgery and review the clinical and imaging findings of these hernias.