Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study.

BACKGROUND: Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management. METHODS: In this multicentre, two-arm, randomised study, we recruited men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia. Patients were randomly assigned to conventional imaging with CT and bone scanning or gallium-68 PSMA-11 PET-CT. First-line imaging was done within 21 days following randomisation. Patients crossed over unless three or more distant metastases were identified. The primary outcome was accuracy of first-line imaging for identifying either pelvic nodal or distant-metastatic disease defined by the receiver-operating curve using a predefined reference-standard including histopathology, imaging, and biochemistry at 6-month follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry, ANZCTR12617000005358. FINDINGS: From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. PSMA PET-CT had a 27% (95% CI 23-31) greater accuracy than that of conventional imaging (92% [88-95] vs 65% [60-69]; p<0·0001). We found a lower sensitivity (38% [24-52] vs 85% [74-96]) and specificity (91% [85-97] vs 98% [95-100]) for conventional imaging compared with PSMA PET-CT. Subgroup analyses also showed the superiority of PSMA PET-CT (area under the curve of the receiver operating characteristic curve 91% vs 59% [32% absolute difference; 28-35] for patients with pelvic nodal metastases, and 95% vs 74% [22% absolute difference; 18-26] for patients with distant metastases). First-line conventional imaging conferred management change less frequently (23 [15%] men [10-22] vs 41 [28%] men [21-36]; p=0·008) and had more equivocal findings (23% [17-31] vs 7% [4-13]) than PSMA PET-CT did. Radiation exposure was 10·9 mSv (95% CI 9·8-12·0) higher for conventional imaging than for PSMA PET-CT (19·2 mSv vs 8·4 mSv; p<0·001). We found high reporter agreement for PSMA PET-CT (κ=0·87 for nodal and κ=0·88 for distant metastases). In patients who underwent second-line image, management change occurred in seven (5%) of 136 patients following conventional imaging, and in 39 (27%) of 146 following PSMA PET-CT. INTERPRETATION: PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning. FUNDING: Movember and Prostate Cancer Foundation of Australia. VIDEO ABSTRACT.

Patterns of failure and prognostic factor analyses in locally advanced cervical cancer patients staged by positron emission tomography and treated with curative intent.

PURPOSE: The aim of this retrospective analysis was to assess whether parameters derived from magnetic resonance imaging (MRI) and positron emission tomography (PET) provide incremental prognostic value compared with International Federation of Gynecology and Obstetrics (FIGO) stage in cervix cancer patients treated with curative intent using concurrent chemoradiotherapy. MATERIALS AND METHODS: This was a retrospective study of patients with locoregionally advanced cervical cancer staged by examination under anesthesia and pretreatment MRI and PET. Potential prognostic factors examined were derived from either clinical evaluation (age, FIGO stage, clinical diameter, histology), MRI (corpus invasion, tumor volume), or PET (lymph node metastasis). Outcome measures examined were overall survival, relapse-free survival, time to failure, local failure, nodal failure, and distant failure. RESULTS: There were 206 eligible patients. The mean potential follow-up was 4.4 years. At 5 years, for all patients, overall survival rate was 59%. For all outcome measures apart from local failure, for which adenocarcinoma histology was the most powerful adverse prognostic factor (HR, 4.29; P < 0.0001), lymph node status on PET was the dominant unifactor and multifactor prognostic factor. Corpus involvement on MRI was significantly associated with nodal involvement on PET but of MRI-derived parameters only tumor volume has prognostic value, limited to time to failure and nodal failure. CONCLUSIONS: Nodal status on PET was the major predictor of outcome in locally advanced cervix cancer treated with chemoradiation and was superior to FIGO staging. Tumor volume measured from MRI appears to be an important predictor of loco-regional relapse.

[Clinical application of (18)F-FDG PET/CT to staging and treatment effectiveness monitoring of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET/CT could increase the accuracy of diagnosis, staging, and treatment effectiveness monitoring of many malignant diseases, such as lung cancer and esophageal cancer. This study was to evaluate the clinical application of (18)F-FDG PET/CT to the staging, restaging, and treatment effectiveness monitoring of nasopharyngeal carcinoma (NPC). METHODS: The reports of whole body (18)F-FDG PET/CT scans, performed from Feb. 2002 to Dec. 2005 on 43 NPC patients (26 men and 17 women with median age of 52 years) in Peter MacCallum Cancer Center, were reviewed. The final diagnoses were made according to medical records, pathologic reports and follow-up information. The accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of (18)F-FDG PET/CT, CT and MRI were calculated and analyzed. RESULTS: The accuracy, specificity, sensitivity, PPV, and NPV of (18)F-FDG PET/CT were 95.3%, 100.0%, 85.7%, 93.8%, and 100.0%, respectively; those of CT and MRI were 65.5%, 79.4%, 64.7%, 81.8%, and 57.9%, respectively. The results of (18)F-FDG PET/CT led to changes in the medical management of 2 staged patients, and 7 restaged patients and 5 patients in monitoring group. (18)F-FDG PET/CT scan affected the therapy plan of 3 restaged patients and 11 patients in monitoring group. Two cases of second primary malignancies(1 case of thyroid carcinoma and 1 case of low grade gastric carcinoma) were detected by (18)F-FDG PET/CT scan. CONCLUSION: (18)F-FDG PET/CT is better than conventional imaging in N and M staging and treatment effectiveness monitoring of NPC.

How do oncologists deal with incidental abnormalities on whole-body fluorine-18 fluorodeoxyglucose PET/CT?

BACKGROUND: Combined positron emission tomography (PET)/computed tomography (CT) using fluorine-18 fluorodeoxyglucose (FDG) is an exciting technique for cancer evaluation, but false-positive results are a recognized limitation. The aim of the study was to evaluate how oncologists deal with focal extrathyroidal FDG abnormalities considered by imaging specialists to be unrelated to the referral indication. METHODS: PET scan reports from a 12-month period from August 2002 to July 2003 in 1727 consecutive patients (mean age, 63 years) were reviewed. Incidental, nonphysiologic FDG abnormalities were classified based on the report conclusion. The frequency with which such abnormalities were investigated by oncologists and the final diagnosis were compared with the imaging diagnosis with a minimum potential follow-up of 2 years (mean, 27.5 months). RESULTS: Incidental FDG abnormalities were reported in 199 (12%) of 1727 patients, including 181 with adequate follow-up. Of 59 cases with a suspected second malignancy, 34 (58%) were actively investigated, with 14 confirmed, 7 unexpected metastatic sites, and 10 other active pathologies. Only 1 further cancer was subsequently detected in the 25 (42%) patients not actively investigated. Conversely, of 122 sites presumed to be benign, only 10 (8%) were actively investigated. Only 2 were proven to relate to malignancy. CONCLUSIONS: Although incidental abnormalities were common, most were benign and appropriately categorized by experienced readers. For actively investigated extrathyroidal abnormalities, a neoplastic basis was confirmed in over 60% of cases. Conversely, for cases deemed most likely benign by the PET/CT report or after review of readily available clinical information by the referring oncologist, the rate of malignancy was less than 2%.