Observation With or Without Subsequent Salvage Therapy for Pathologically Node-positive Prostate Cancer With Negative Conventional Imaging: Results From a Large Multicenter Cohort.

Background and objective: More than 10% of patients with negative clinical metastatic status (cN0M0) on conventional imaging for prostate cancer (PCa) harbor lymph node involvement (pN+) at final pathology following radical prostatectomy (RP) and lymphadenectomy. Our aim was to assess outcomes of initial observation for cN0M0 pN+ PCa and identify prognostic factors that may help in clinical decision-making. Methods: We performed a retrospective multicenter study of patients with cN0M0 PCa on conventional imaging (computed tomography and/or magnetic resonance imaging, and a bone scan) who were found to have pN+ disease at RP between 2000 and 2021. Biochemical recurrence (BCR) and systemic progression/recurrence were the primary outcomes. Kaplan-Meier curves and Cox proportional hazards model were used for survival and multivariate analysis. Key findings and limitations: A total of 469 men were included in this retrospective multicenter trial. Median prostate-specific antigen (PSA) was 10.1 ng/ml (interquartile range [IQR] 6.6-18.0). Among these patients, 56% had grade group ≥4, 53.7% had stage ≥pT3b, 42.6% had positive margins, and 19.6% had PSA persistence. The median number of positive nodes and of nodes removed were 1 (IQR 1-3) and 20 (14-28), respectively. At median follow-up of 41 mo, 48.5% experienced BCR. The 5-yr BCR-free survival rate was 31.7% (95% confidence interval [CI] 26.33-37.1%). Salvage treatments were needed in 211 patients and included radiotherapy (RT; n = 53), RT + androgen deprivation therapy (ADT; n = 88), ADT alone (n = 68), and salvage lymphadenectomy (n = 2). The 5-yr estimated survival rates were 66.3% (95% CI 60.4-72.1) for metastasis-free survival, 97.7% (95% CI 95.5-99.8%) for cancer-specific survival, and 95.3% (95% CI 92.4-98.1%) for overall survival. On multivariable analysis, PSA persistence was an independent predictor of BCR (odds ratio [OR] 51.8, 95% CI 12.2-219.2), exit from observation (OR 8.5, 95% CI 4.4-16.5), and systemic progression (OR 3.0, 95% CI 1.771-4.971). Conclusions: Initial observation in the management of pN+ cN0M0 PCa is feasible and has excellent survival rates in the intermediate term. Patients with worse disease features, especially PSA persistence, have a higher likelihood of recurrence and progression and may be candidates for more aggressive upfront management. Patient summary: We investigated the value of initial observation for men with prostate cancer with negative scan findings for metastasis who were then found to have positive lymph nodes after surgery to remove the prostate. Our results show that initial observation is a good option for patients with less aggressive prostate cancer features.

Comparative Performance of 68Ga-PSMA-11 PET/CT and Conventional Imaging in the Primary Staging of High-Risk Prostate Cancer Patients Who Are Candidates for Radical Prostatectomy.

This prospective study aimed to (1) compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with respect to conventional imaging (computed tomography (CT) and bone scintigraphy (BS)) in the primary staging of high-risk prostate cancer (PCa) patients and (2) validate PSMA-PET/CT accuracy in pelvic nodal staging in comparison with postoperative histopathology and assess PSMA-PET/CT's impact on patient management. Sixty castration-sensitive high-risk (ISUP 4-5 and/or PSA > 20 ng/mL and/or cT3) PCa patients eligible for radical prostatectomy were enrolled (median PSA 10.10 [IQR: 6.22-17.95] ng/mL). PSMA-PET/CT, compared with CT, identified nodal (N) and/or distant metastases (M1) in 56.7% (34/60) vs. 13.3% (8/60) (p < 0.001) of patients: N + 45% vs. 13.3% (p < 0.001), M1a 11.7% vs. 1.7% (p = 0.03), M1b 23.3% vs. 1.7% (p < 0.001). Compared with BS, PSMA-PET/CT localized unknown skeletal metastases in 15% (9/60) of cases, with no false negative findings. Overall, PSMA-PET/CT led to a TNM upstaging in 45.0% (27/60) of cases, with no evidence of downstaging, resulting in a change in management in up to 28.8% (17/59) of patients. Compared with histopathology data (n = 32 patients), the per-patient accuracy of PSMA-PET/TC for detecting pelvic nodal metastases was 90.6%. Overall, the above evidence supports the use of PSMA-PET/CT in the diagnostic workup of high-risk prostate cancer staging.

Diagnostic Performance of F-18 FDG PET/CT in the Detection of Recurrent Colorectal Cancer: Correlation with Biochemical Markers and Conventional Imaging Modalities.

Background/Objectives: Although the role of PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of F-18 FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, a retrospective study was performed including 134 CRC patients referred for PET/CT imaging on the suspicion of recurrence, based on elevated CEA and/or CA 19-9 and/or equivocal CIM findings. According to our institution's Tumor Board CRC protocol, after the initial treatment, which was dependent on the TNM stage (neoadjuvant therapy, primary resection, or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy, every six months. The statistics, including univariate and multivariate analyses were conducted using the IBM SPSS 20.0 statistical software. p-values < 0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. PET/CT showed high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA showed a high sensitivity of 98.1% but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy for CA 19-9 and CIM for diagnosis of CRC recurrence were 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p < 0.001), 0.844 (95% CI: 0.772-0.916; p < 0.001), 0.753 (95% CI: 0.612-0.844; p < 0.001), and 0.547 (95% CI: 0.442-0.652; p = 0.358), respectively. Univariate analysis showed that both PET/CT and CIM positive results were highly associated with CRC recurrence (p < 0.001 and p < 0.001, respectively). At the same time, gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) had no significance (p = 0.211, p = 0.158, p = 0.583, and p = 0.201, respectively). Our multivariate analysis showed that independent predictors for CRC recurrence are positive PET/CT scans (p < 0.001), positive CIM results (p = 0.001), and elevated CA 19-9 levels (p = 0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p = 0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting the CRC recurrence (p = 0.023). Conclusions: F-18 FDG PET/CT showed high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the post-operative follow-op in patients with elevated tumor markers.

The prognostic role of next-generation imaging-driven upstaging in newly diagnosed prostate cancer patients.

PURPOSE: Phase III evidence showed that next-generation imaging (NGI), such as prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), provides higher diagnostic accuracy than bone scan and contrast-enhanced computed tomography (conventional imaging, CI) in the primary staging of intermediate-to-high-risk prostate cancer (PCa) patients. However, due to the lack of outcome data, the introduction of NGI in routine clinical practice is still debated. Analysing the oncological outcome of patients upstaged by NGI (though managed according to CI) might shed light on this issue, supporting the design of randomised trials comparing the effects of treatments delivered based on NGI vs. CI. METHODS: We prospectively enrolled a cohort of 100 biopsy-proven intermediate-to-high-risk PCa patients staged with CI and PSMA PET/CT (though managed according to the CI stage), to assess the frequency of the stage migration phenomenon. Stage migration was then assessed as biochemical recurrence-free survival (bRFS) predictor. RESULTS: Three patients were lost at follow-up after imaging. PSMA PET/CT upstaged 26.8% of patients compared to CI, while it downstaged 6.1% of patients. Notably, 50% of patients excluded from surgery due to the presence of bone metastases at CI would have been treated with radical-intent approaches if PSMA PET/CT had guided the treatment choice. After a median follow-up of 6 months of surgically treated patients, 22/83 (26.5%) had biochemical recurrence (BCR). PSMA PET/CT-driven upstaging determined a significant risk increase for BCR (HR:3.41, 95%CI:1.21-9.56, p = 0.019). Including stage migration in a univariable and multivariable model identified PSMA PET/CT-upstaging as an independent predictor of bRFS. CONCLUSIONS: In conclusion, implementing NGI for staging purposes improves the prediction of bRFS. Although phase III evidence is still needed, this advancement suggests that NGI may better identify patients who would benefit from local treatments than those who may achieve better oncological outcomes through systemic treatment.

18F-fluoro-2-deoxy-2-d-glucose PET-CT (FDG PET-CT) in staging of high-risk renal and urothelial bladder cancers (COPPER-T) trial protocol.

Background and Study Design: Role of 18F-fluoro-2-deoxy-2-d-glucose positron emission tomography-computed tomography (FDG PET-CT) in evaluation of renal cell cancers (RCC) and urinary bladder cancers is not standardized, and the COPPER-T trial, which is a single centre prospective randomized study, was designed to compare it with conventional imaging for staging of clinically localized high risk RCC and urinary bladder carcinoma (Stage T2 and above). Patients and Methods: There will be two subgroups of patients: RCC and urinary bladder carcinoma. In each of these, the patients will be randomized to either Arm A or Arm B. In each of the arms, each patient will be subjected to diagnostic imaging by FDG PET-CT. The CT scan will be a contrast-enhanced scan like that in conventional staging. A radiologist and nuclear medicine specialist will report the scan independently. The radiologist will not have access to the PET scan sequences and will only review the contrast-enhanced computed tomography (CECT) images. In Arm A, the report of the conventional imaging modality, that is, CECT and bone scan if done, will be reviewed first by the clinician, and based on this report, a management plan will be made. Then, the PET-CT report will be reviewed, and change in the management plan will be noted. New findings or equivocal findings if any in the PET-CT report would be noted. In Arm B, the report of the PET-CT report will be reviewed first by the clinicians, and a management plan will be made. Then, the CECT and/or bone scan reports will be reviewed, and any change in the management plan will be noted. Outcome and Significance: Final analysis of the data after completion of the trial will help in clarifying the role of FDG PET-CT in high risk RCC and transitional cell carcinoma (TCC) of the bladder, its diagnostic accuracy compared with conventional imaging and the impact of using it on patient management.

PET/CT and Conventional Imaging for the Assessment of Neuroendocrine Prostate Cancer: A Systematic Review.

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a rare neoplasm, and the role of both conventional imaging (CI) and positron emission tomography/computed tomography (PET/CT) for its assessment has not been clearly evaluated and demonstrated. The aim of this systematic review was to analyze the diagnostic performances of these imaging modalities in this setting. METHODS: A wide literature search of the PubMed/MEDLINE, Scopus, and Web of Science databases was made to find relevant published articles about the role of CI and PET/CT for the evaluation of NEPC. RESULTS: 13 studies were included in the systematic review. PET/CT imaging with different radiopharmaceuticals has been evaluated in many studies (10) compared to CI (3 studies), which has only a limited role in NEPC. Focusing on PET/CT, a study used [18F]FDG, labeled somatostatin analogs were used in 5 cases, a study used [68Ga]Ga-FAPI-04, [68Ga]Ga-PSMA-11 was evaluated in a single case, and two works used different tracers. CONCLUSION: Published data on the role of PET/CT for the assessment of NEPC are limited. At present, it is still uncertain which tracer performs best, and although [18F]FDG has been evaluated and seems to offer some advantages in availability and clinical staging, other tracers may be more useful to understand tumor biology or identify targets for subsequent radioligand therapy. Further research is therefore desirable. In contrast, data are still limited to draw a final conclusion on the role and the specific characteristics of CI in this rare form of neoplasm, and therefore, more studies are needed in this setting.

Fluorodeoxyglucose positron emission tomography (18F-FDG PET)-computed tomography (CT) in the initial staging of bladder cancer: a single institution experience.

BACKGROUND: The purpose of this study was to assess the usefulness of fluorodeoxyglucose positron emission tomography (18F-FDG PET)-computed tomography (CT) scan for staging urinary bladder cancer. The study also sought to determine the effect of 18F-FDG PET/CT on management decisions and its implications for patient care. METHODS: A total of 133 patients with bladder cancer who had both conventional imaging and 18F-FDG PET/CT for initial staging were identified. All 18F-FDG-PET/CT findings were classified as true positive, true negative, false positive, or false negative based on their potential to impact the intent of treatment. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated using the standard definition. Furthermore, the rate of change in therapy intent was determined for the entire sample and for subgroups with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) patients. RESULTS: The overall concordance rate between PET/CT and conventional imaging was around 54%. On conventional images, 18% of patients had localized disease, which was upstaged in 6.8% of cases using 18F-FDG PET/CT. Pelvic lymph node involvement was detected in 18.8% of cases using conventional imaging, which was downstaged to localized disease in 4.5% of cases using 18F-FDG PET/CT. While 63.2% of patients had systemic disease on a CT scan, 24.7% of cases were downstaged using PET/CT. Overall, the rate of change in therapy intent was 26.3% for the entire sample, 24.5% for NMIBC subgroup, and 27.3% for MIBC patients. CONCLUSIONS: The study found that 18F-FDG PET/CT is an effective and accurate tool for staging bladder cancer in newly diagnosed patients. Approximately one quarter of patients had a change in management intent based on 18F-FDG PET/CT results. The study suggests that PET/CT should be used as a standard for newly diagnosed patients, but more research is needed to confirm this.

Impact of non-regional lymph node metastases accurately revealed on 18F-PSMA-1007 PET/CT in the clinical management of metastatic hormone-sensitive prostate cancer.

BACKGROUND: Non-regional lymph node (NRLN) metastases has shown increasing importance in the prognosis evaluation and clinical management of primary metastatic hormone-sensitive prostate cancer (mHSPC). Hence, this study aimed to investigate the concordance rates between 18F-PSMA-1007 PET/CT and conventional imaging (CI) in revealing NRLN metastases, and explore the impact of NRLN metastases on the management of primary mHSPC. METHODS: The medical records of 224 patients with primary mHSPC were retrospectively reviewed, including 101 patients (45.1%) only received CI for TNM classification, 24 patients (10.7%) only received 18F-PSMA-1007 PET/CT, and 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI. Among patients who received 18F-PSMA-1007 PET/CT and CI before initial treatment, the concordance rates between 18F-PSMA-1007 PET/CT and CI were analyzed. The high-volume disease was defined as the presence of visceral metastases and/or ≥ 4 bone metastases (≥ 1 beyond the vertebral bodies or the pelvis) based on the findings of 18F-PSMA-1007 PET/CT and/or CI. The primary endpoint was progression-free survival (PFS), and Cox regression analyses were performed to explore independent predictors of PFS. RESULTS: A total of 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI, the concordance rate in revealing NRLN metastases between 18F-PSMA-1007 PET/CT and CI was only 61.62%, and Cohen's kappa coefficient was as low as 0.092. Moreover, 18F-PSMA-1007 PET/CT detected an additional 37 of 94 (39.4%) patients with positive NRLNs who were negative on CI. Cox regression revealed that androgen deprivation therapy (ADT), N1, high-volume, NRLN and visceral metastases were associated with worse PFS (all P < 0.05) in 224 patients. Furthermore, in patients with low-volume disease, the median PFS of patients with NRLN metastases was significantly shorter than that of patients without NRLN metastases (19.5 vs. 27.5 months, P = 0.01), while the difference between patients with low-volume plus NRLN metastases and high-volume disease was not significant (19.5 vs. 16.9 months, P = 0.55). Moreover, early docetaxel chemotherapy significantly prolonged the PFS of these patients compared with ADT alone (20.7 vs. 12.3 months, P = 0.008). CONCLUSION: NRLN metastases could be accurately revealed by 18F-PSMA-1007 PET/CT, which should be considered a high-volume feature, especially concomitant with bone metastases. Furthermore, patients with low-volume plus NRLN metastases may be suitable for more intensive treatment, such as early docetaxel chemotherapy.

An Overview of Hepatocellular Carcinoma Surveillance Focusing on Non-Cirrhotic NAFLD Patients: A Challenge for Physicians.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide and it ranges from simple steatosis to hepatocellular carcinoma (HCC). HCC represents the first liver tumor and the third source of cancer death. In the next few years, the prevalence of NAFLD and consequently of HCC is estimated to increase, becoming a major public health problem. The NAFLD-HCC shows several differences compared to other causes of chronic liver disease (CLD), including the higher percentage of patients that develop HCC in the absence of liver cirrhosis. In HCC surveillance, the international guidelines suggest a six months abdominal ultrasound (US), with or without alpha-fetoprotein (AFP) evaluation, in patients with cirrhosis and in a subgroup of patients with chronic hepatitis B infection. However, this screening program reveals several limitations, especially in NAFLD patients. Thus, new biomarkers and scores have been proposed to overcome the limits of HCC surveillance. In this narrative review we aimed to explore the differences in the HCC features between NAFLD and non-NAFLD patients, and those between NAFLD-HCC developed in the cirrhotic and non-cirrhotic liver. Finally, we focused on the limits of tumor surveillance in NAFLD patients, and we explored the new biomarkers for the early diagnosis of HCC.

Evaluation of different imaging modalities for axillary lymph node staging in breast cancer patients to provide a personalized and optimized therapy algorithm.

PURPOSE: The reliable detection of tumor-infiltrated axillary lymph nodes for breast cancer [BC] patients plays a decisive role in further therapy. We aimed to find out whether cross-sectional imaging techniques could improve sensitivity for pretherapeutic axillary staging in nodal-positive BC patients compared to conventional imaging such as mammography and sonography. METHODS: Data for breast cancer patients with tumor-infiltrated axillary lymph nodes having received surgery between 2014 and 2020 were included in this study. All examinations (sonography, mammography, computed tomography [CT] and magnetic resonance imaging [MRI]) were interpreted by board-certified specialists in radiology. The sensitivity of different imaging modalities was calculated, and binary logistic regression analyses were performed to detect variables influencing the detection of positive lymph nodes. RESULTS: All included 382 breast cancer patients had received conventional imaging, while 52.61% of the patients had received cross-sectional imaging. The sensitivity of the combination of all imaging modalities was 68.89%. The combination of MRI and CT showed 63.83% and the combination of sonography and mammography showed 36.11% sensitivity. CONCLUSION: We could demonstrate that cross-sectional imaging can improve the sensitivity of the detection of tumor-infiltrated axillary lymph nodes in breast cancer patients. Only the safe detection of these lymph nodes at the time of diagnosis enables the evaluation of the response to neoadjuvant therapy, thereby allowing access to prognosis and improving new post-neoadjuvant therapies.

The role of 18F-FDG PET/CT in patients with synchronous multiple primary malignant neoplasms occurring at the same time.

Background: Synchronous multiple primary malignant neoplasms occurring at the same time (SMPMNS) are not currently uncommon in clinical oncological practice; however, the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for SMPMNS needs further elucidation. Purpose: This study aimed to evaluate the application of 18F-FDG PET/CT in patients with SMPMNS. Materials and methods: The clinical and imaging data of 37 patients with SMPMNS who had undergone 18F-FDG PET/CT from October 2010 to December 2020 were retrospectively analyzed. The kappa consistency test was applied to evaluate the consistency of the diagnostic performance between PET/CT and conventional imaging (CI). The sensitivity, specificity, and accuracy of PET/CT and CI in the detection of metastatic lesions were compared. Results: This retrospective diagnostic study included 74 lesions identified in 37 patients with SMPMNS, with 94.6% of patients having double primary tumors. Of the incidences of SMPMNS, 18.9% occurred in the same organ system, with respiratory tumors being the most common type of neoplasm (43.2%) and the lung being the most common primary site (40.5%). The overall survival of SMPMNS patients without metastases was longer than that of those with metastases (χ 2 = 12.627, p = 0.000). The maximum standardized uptake value (SUVmax), the SUVmax ratio (larger SUVmax/smaller SUVmax), and the difference index of SUVmax (DISUVmax) [(larger SUVmax - smaller SUVmax)/larger SUVmax] of the primary lesions ranged from 0.9 to 41.7 (average = 12.3 ± 7.9), from 0.3 to 26.7 (average = 4.4 ± 6.9), and from 0.0% to 96.3% (average = 50.3% ± 29.3%), respectively. With regard to diagnostic accuracy, PET/CT and CI showed poor consistency (κ = 0.096, p = 0.173). For the diagnosis of primary lesions (diagnosed and misdiagnosed), PET/CT and CI also showed poor consistency (κ = 0.277, p = 0.000), but the diagnostic performance of PET/CT was better than that of CI. In the diagnosis of metastases, the patient-based sensitivity, specificity, and accuracy of PET/CT were 100.0%, 81.8%, and 89.2%, respectively, while those of CI were 73.3%, 100.0%, 89.2%, respectively. The sensitivity and specificity values were significantly different, with PET/CT having higher sensitivity (p = 0.02) and CI showing higher specificity (p = 0.02). Conclusions: 18F-FDG PET/CT improves the diagnostic performance for SMPMNS and is a good imaging modality for patients with SMPMNS.

The Role of [18F]F-Choline PET/CT in the Initial Management and Outcome Prediction of Prostate Cancer: A Real-World Experience from a Multidisciplinary Approach.

Initial staging of prostate cancer (PCa) is usually performed with conventional imaging (CI), involving computed tomography (CT) and bone scanning (BS). The aim of this study was to analyze the role of [18F]F-choline positron emission tomography (PET)/CT in the initial management and outcome prediction of PCa patients by analyzing data from a multidisciplinary approach. We retrospectively analyzed 82 patients who were discussed by the uro-oncology board of the University Hospital of Ferrara for primary staging newly diagnosed PCa (median age 72 (56-86) years; median baseline prostate specific antigen (PSA) equal to 8.73 ng/mL). Patients were divided into three groups based on the imaging performed: group A = only CI; group B = CI + [18F]F-choline PET/CT; group C = only [18F]F-choline PET/CT. All data on imaging findings, therapy decisions and patient outcomes were retrieved from hospital information systems. Moreover, we performed a sub-analysis of semiquantitative parameters extracted from [18F]F-choline PET/CT to search any correlation with patient outcomes. The number of patients included in each group was 35, 35 and 12, respectively. Patients with higher values of initial PSA were subjected to CI + PET/CT (p = 0.005). Moreover, the use of [18F]F-choline PET/CT was more frequent in patients with higher Gleason score (GS) or ISUP grade (p = 0.013). The type of treatment performed (surgery n = 33; radiation therapy n = 22; surveillance n = 6; multimodality therapy n = 6; systemic therapy n = 13; not available n = 2) did not show any relationship with the modality adopted to stage the disease. [18F]F-choline PET/CT induced a change of planned therapy in 5/35 patients in group B (14.3%). Moreover, patients investigated with [18F]F-choline PET/CT alone demonstrated longer biochemical recurrence (BCR)-free survival (30.8 months) in comparison to patients of groups A and B (15.5 and 23.5 months, respectively, p = 0.006), probably due to a more accurate selection of primary treatment. Finally, total lesion choline kinase activity (TLCKA) of the primary lesion, calculated by multiplying metabolic tumor volume and mean standardized uptake value (SUVmean), was able to more effectively discriminate patients who had recurrence after therapy compared to those without (p = 0.03). In our real-world experience [18F]F-choline PET/CT as a tool for the initial management of PCa had a relevant impact in terms of therapy selection and was associated with longer BCR-free survival. Moreover, TLCKA of the primary lesion looks a promising parameter for predicting recurrence after curative therapy.

Apalutamide, Darolutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC): A Critical Review.

Nonmetastatic castration-resistant prostate cancer (nmCRPC) represents a condition in which patients with prostate cancer show biochemical progression during treatment with androgen-deprivation therapy (ADT) without signs of radiographic progression according to conventional imaging. The SPARTAN, ARAMIS and PROSPER trials showed that apalutamide, darolutamide and enzalutamide, respectively, prolong metastasis-free survival (MFS) and overall survival (OS) of nmCRPC patients with a short PSA doubling time, and these antiandrogens have been recently introduced in clinical practice as a new standard of care. No direct comparison of these three agents has been conducted to support treatment choice. In addition, a significant proportion of nmCRPC on conventional imaging is classified as metastatic with new imaging modalities such as the prostate-specific membrane antigen positron emission tomography (PSMA-PET). Some experts posit that these "new metastatic" patients should be treated as mCRPC, resizing the impact of nmCRPC trials, whereas other authors suggest that they should be treated as nmCRPC patients, based on the design of pivotal trials. This review discusses the most convincing evidence regarding the use of novel antiandrogens in patients with nmCRPC and the implications of novel imaging techniques for treatment selection.

Role of Ga-68 DOTANOC Positron Emission Tomography/ Computed Tomography Scan in Clinical Management of Patients with Neuroendocrine Tumors and its Correlation with Conventional Imaging- Experience in a Tertiary Care Center in India.

Purpose of Study: Aim of the study was to evaluate the role of 68Gallium-DOTANOC positron emission tomography/computed tomography (68Ga-DOTANOC PET/CT), a pan somatostatin receptor (SSTR) analog in the clinical management of patients with neuroendocrine tumors (NETs) and its correlation with conventional imaging. Materials and Methods: We retrospectively evaluated 69 patients of known/suspected NETs who underwent 68Ga-DOTANOC PET/CT scan for tumor localization (n = 15), stage modification (primary staging, n = 26 and restaging, n = 25) and therapy monitoring (n = 3). We also compared PET scan with conventional imaging as reference standard and evaluated the impact of PET/CT in the clinical management of patients. Results: The concordant findings on 68Ga-DOTANOC PET/CT and conventional imaging seen in 33 and discordant in 36 patients. Among discordant group, disease was upstaged in 32 patients; down staged in 3 patients; no stage change in one patient. PET/CT localized primary tumor in 4 patients. Among patients with raised tumor markers (39/69), PET was positive in 29 and negative in 10 patients. Patients were followed for mean duration of 27 months to assess management. We found strong agreement between positive PET and raised tumor markers (Kappa value = 0.8). Sensitivity and specificity of PET/CT for primary tumor localization, stage modification, and therapy monitoring was >90% (P < 0.05). Conclusions: Study shows that DOTANOC, a broad spectrum SSTRs binding peptide labeled with Ga-68 in PET/CT scan is an excellent modality in the management of NETs patients.

The Continuum of Metastatic Prostate Cancer: Interpreting PSMA PET Findings in Recurrent Prostate Cancer.

Conventional imaging has been the standard imaging modality for assessing prostate cancer recurrence and is utilized to determine treatment response to therapy. Molecular imaging with PSMA PET-CT has proven to be more accurate, sensitive, and specific at identifying pelvic or distant metastatic disease, resulting in earlier diagnosis of advanced disease. Since advanced disease may not be seen on conventional imaging, due to its lower sensitivity, but can be identified by molecular imaging, this reveals that metastatic prostate cancer occurs on a continuum from negative PSMA PET-CT and negative conventional imaging to positive PSMA PET-CT and positive conventional imaging. Understanding this continuum, the accuracy of these modalities, and treatment related outcomes based on imaging, will allow the clinician to counsel patients on management. This review will highlight the differences in conventional and molecular imaging in prostate cancer and how PSMA PET-CT can be used for the management of prostate cancer patients in different clinical scenarios, while providing cautionary notes for overtreatment.

Identifying the Best Candidates for Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography as the Primary Staging Approach Among Men with High-risk Prostate Cancer and Negative Conventional Imaging.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is an emerging imaging modality with greater sensitivity and specificity over conventional imaging for prostate cancer (PCa) staging. Using data from two prospective trials (NCT03368547 and NCT04050215), we explored predictors of overall upstaging (nodal and metastatic) by PSMA PET/CT among patients with cN0M0 National Comprehensive Cancer Network high-risk PCa on conventional imaging (n = 213). Overall, 21.1%, 8.9%, and 23.9% of patients experienced nodal, metastatic, and overall upstaging, respectively, without histologic confirmation. On multivariable analysis, Gleason grade group (GG) and percent positive core (PPC) on systematic biopsy significantly predict overall upstaging (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.33-3.45; p = 0.002; and OR 1.03, 95% CI 1.01-1.04; p < 0.001). Overall upstaging was significantly more frequent among men with GG 5 disease (33.0% vs. 17.6%; p = 0.0097) and PPC ≥50% (33.0% vs 15.0%; p = 0.0020). We constructed a nomogram that predicts overall upstaging using initial prostate-specific antigen, PPC, GG, and cT stage, with coefficients estimated from a standard logistic regression model (using maximum likelihood estimation). It is internally validated with a tenfold cross-validated area under the receiver operating characteristic curve estimated at 0.74 (95% CI 0.67-0.82). In our cohort, 90% of patients who had a nomogram-estimated risk below the cutoff of 22% for overall upstaging could have been spared PSMA PET/CT as our model correctly predicted no upstaging. In other words, the predictive model only missed 10% of patients who would otherwise have benefitted from PSMA PET/CT. PATIENT SUMMARY: We analyzed predictors of overall upstaging (lymph node or/and metastasis) by prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) from conventional imaging in men with high-risk prostate cancer undergoing initial staging deemed free of disease in the lymph nodes and distant metastasis by conventional imaging techniques. We found that the pathologic grade and disease burden in a prostate biopsy are associated with upstaging. We also developed a tool that predicts the probability of upstaging according to an individual patient's characteristics. Our study may help in defining patient groups who are most likely to benefit from the addition of a PSMA PET/CT scan.

Value of 18F-FES PET in Solving Clinical Dilemmas in Breast Cancer Patients: A Retrospective Study.

Breast cancer (BC) is a heterogeneous disease in which estrogen receptor (ER) expression plays an important role in most tumors. A clinical dilemma may arise when a metastasis biopsy to determine the ER status cannot be performed safely or when ER heterogeneity is suspected between tumor lesions. Whole-body ER imaging, such as 16α-18F-fluoro-17ß-estradiol (18F-FES) PET, may have added value in these situations. However, the role of this imaging technique in routine clinical practice remains to be further determined. Therefore, we assessed whether the physician's remaining clinical dilemma after the standard workup was solved by the 18F-FES PET scan. Methods: This retrospective study included 18F-FES PET scans of patients who had (or were suspected to have) ER-positive metastatic BC and for whom a clinical dilemma remained after the standard workup. The scans were performed at the University Medical Center of Groningen between November 2009 and January 2019. We investigated whether the physician's clinical dilemma was solved, defined either as solving the clinical dilemma through the 18F-FES PET results or as basing a treatment decision directly on the 18F-FES PET results. In addition, the category of the clinical dilemma was reported, as well as the rate of 18F-FES-positive or -negative PET scans, and any correlation to the frequency of solved dilemmas was determined. Results: One hundred 18F-FES PET scans were performed on 83 patients. The clinical dilemma categories were inability to determine the extent of metastatic disease or suspected metastatic disease with the standard workup (n = 52), unclear ER status of the tumor (n = 31), and inability to determine which primary tumor caused the metastases (n = 17). The dilemmas were solved by 18F-FES PET in 87 of 100 scans (87%). In 81 of 87 scans, a treatment decision was based directly on 18F-FES PET results (treatment change, 51 scans; continuance, 30 scans). The frequency of solved dilemmas was not related to the clinical dilemma category (P = 0.334). However, the frequency of solved dilemmas was related to whether scans were 18F-FES-positive (n = 63) or 18F-FES-negative (n = 37; P < 0.001). Conclusion: For various indications, the 18F-FES PET scan can help to solve most clinical dilemmas that may remain after the standard workup. Therefore, the 18F-FES PET scan has added value in BC patients who present the physician with a clinical dilemma.

Nuclear Imaging for Bone Metastases in Prostate Cancer: The Emergence of Modern Techniques Using Novel Radiotracers.

Accurate staging of prostate cancer (PCa) at initial diagnosis and at biochemical recurrence is important to determine prognosis and the optimal treatment strategy. To date, treatment of metastatic PCa has mostly been based on the results of conventional imaging with abdominopelvic computed tomography (CT) and bone scintigraphy. However, these investigations have limited sensitivity and specificity which impairs their ability to accurately identify and quantify the true extent of active disease. Modern imaging modalities, such as those based on the detection of radioactively labeled tracers with combined positron emission tomography/computed tomography (PET/CT) scanning have been developed specifically for the detection of PCa. Novel radiotracers include 18F-sodium fluoride (NaF), 11C-/18F-fluorocholine (FCH), 18F-fluordihydrotestosterone (FDHT), 68Gallium and 18F-radiolabeled prostate-specific membrane antigen (e.g., 68Ga-PSMA-11, 18F-DCFPyL). PET/CT with these tracers outperforms conventional imaging. As a result of this, although their impact on outcome needs to be better defined in appropriate clinical trials, techniques like prostate-specific membrane antigen (PSMA) PET/CT have been rapidly adopted into clinical practice for (re)staging PCa. This review focuses on nuclear imaging for PCa bone metastases, summarizing the literature on conventional imaging (focusing on CT and bone scintigraphy-magnetic resonance imaging is not addressed in this review), highlighting the prognostic importance of high and low volume metastatic disease which serves as a driver for the development of better imaging techniques, and finally discussing modern nuclear imaging with novel radiotracers.

A Prospective Comparison of 18F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE).

BACKGROUND: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa). OBJECTIVE: To compare standard staging modalities with newer and potentially more accurate imaging modalities. DESIGN, SETTING, AND PARTICIPANTS: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group ≥3 and/or prostate-specific antigen [PSA] ≥20 and/or cT ≥ T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and 18F-prostate-specific membrane antigen-1007 (18F-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging. RESULTS AND LIMITATIONS: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality 18F-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method 18F-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions. CONCLUSIONS: Despite the risk of false positive bone lesions, 18F-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa. PATIENT SUMMARY: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that 18F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (18F-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions.

Case Report: Pleuropulmonary Blastoma in a 2.5-Year-Old Boy: 18F-FDG PET/CT Findings.

Pleuropulmonary blastoma (PPB) is a rare invasive primary malignancy in the thoracic cavity that occurs mainly in infants and children. It is often misdiagnosed and not treated correctly and promptly due to the lack of specificity of clinical symptoms and conventional imaging presentations. We report a 2.5-year-old boy who underwent X-ray chest radiography, chest CT, and 18F-FDG PET/CT. PET/CT images demonstrated a sizeable cystic-solid mass with heterogeneous increased glucose metabolism in the left thoracic cavity. The diagnosis of PPB (type II) was finally confirmed by a CT-guided puncture biopsy of the active tumor tissue. This case highlights the critical role of 18F-FDG PET/CT in the diagnosis of PPB in children.