[18F]DCFPyL PET/CT in detection and localization of recurrent prostate cancer following prostatectomy including low PSA < 0.5 ng/mL.

PURPOSE: The primary aim of this retrospective multicenter analysis was to assess the performance of PSMA PET/CT using [18F]DCFPyL in the detection and localization of recurrent prostate cancer post radical prostatectomy (RP). Particular reference is given to low PSA groups < 0.5 ng/mL to aid discussion around the inclusion of this group in PSMA guidelines and funding pathways. METHODS: Retrospective analysis of combined PSMA database patients from centers in Australia and New Zealand. Two hundred twenty-two patients presenting with recurrence post RP were stratified into five PSA groups (ng/mL): 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥ 2. Lesions detected by [18F]DCFPyL PET/CT were recorded as local recurrence, locoregional nodes, and metastases. RESULTS: Of 222 patients, 155 (69.8%) had evidence of abnormal uptake suggestive of recurrent prostate cancer. The detection efficacies for [18F]DCFPyL PET/CT were 91.7% (44/48) for PSA levels ≥ 2 ng/mL, 82.1% (23/28) for PSA levels 1-1.99 ng/mL, 62.8% (27/43) for PSA levels 0.5-0.99 ng/mL, 58.7% (54/92) for PSA levels 0.2-0.49 ng/mL, and 63.6% (7/11) for PSA levels ≤ 0.2 ng/mL. In those with PSA < 0.5 ng/mL, 47.6% (49/103) had detectable lesions, 71.4% (35/49) had disease confined to the pelvis, 22.4% (11/49) had prostate bed recurrence, 49.0% (24/49) had pelvic lymph nodes, and 28.6% (14/49) had extra pelvic disease. CONCLUSION: [18F]DCFPyL PET/CT has a high detection rate in recurrence following RP even at low PSA levels with similar detection levels in the PSA subgroups < 0.5 ng/mL. Employing rigid PSA thresholds when constructing guidelines for PSMA PET/CT funding eligibility may result in a significant number of patients below such thresholds having delayed or inappropriate treatment.

PEDAL protocol: a prospective single-arm paired comparison of multiparametric MRI and 18F-DCPFyl PSMA PET/CT to diagnose prostate cancer.

INTRODUCTION: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has emerged as valuable imaging to assessing metastatic disease in prostate malignancy. However, there has been limited studies exploring the utility PSMA-PET as primary imaging assessing for index lesions prior to biopsy. The primary objective of this study is to compare the diagnostic accuracy of 18-fluorine PSMA (18F DCFPyL PSMA) PET scans to multiparametric MRI (mpMRI) to detect primary prostate cancer at prostate biopsy. METHODS AND ANALYSIS: The PEDAL trial is a multicentre, prospective, single-arm, paired comparison, non-randomised phase III trial in subjects considered for diagnostic prostate biopsy. Subjects who are eligible for a diagnostic mpMRI prostate will undergo additional same-day 18 F DCFPyl PSMA PET/CT of the chest, abdomen and pelvis. Software coregistration of the mpMRI and PSMA-PET/CT images will be performed. The reporting of the mpMRI prostate, PSMA-PET/CT and PSMA PET/MRI coregistration will be performed blinded. The diagnostic accuracy of PSMA PET/CT alone, and in combination with mpMRI, to detect prostate cancer will be assessed. Histopathology at prostate biopsy will be used as the reference standard. Sample size calculations estimate that 240 subjects will need to be recruited to demonstrate 20% superiority of PSMA-PET/CT. The sensitivity, specificity, positive predictive value and negative predictive value of the combination of mpMRI prostate and PSMA PET/CT compared with targeted and systematic prostate biopsy will be evaluated. It is hypothesised that PSMA PET/CT combined with mpMRI prostate will have improved diagnostic accuracy compared with mpMRI prostate alone for detection of prostate cancer in biopsy-naïve men, resulting in a significant impact on patient management. ETHICS AND DISSEMINATION: This study was approved by the independent Human Research Ethics Committee. Results will be published in peer-reviewed medical journals with eligible investigators will significantly contribute. TRIAL REGISTRATION NUMBER: ACTRN12620000261910.

Assessment of best single sample for finding chlamydia in women with and without symptoms: a diagnostic test study.

OBJECTIVE: To compare vulvovaginal swabs with endocervical swabs as optimal diagnostic sample for detection of Chlamydia trachomatis infection. DESIGN: A diagnostic test study. SETTING: An urban sexual health centre. PARTICIPANTS: 3973 women aged ≥ 16 years requesting testing for sexually transmitted infections. INTERVENTIONS: Participants took a vulvovaginal swab before routine examination, and clinicians took an endocervical swab during examination. MAIN OUTCOME MEASURE: Diagnosis of chlamydia infection with samples analysed using the Aptima Combo-2 assay; positive results confirmed with the Aptima CT assay. RESULTS: Of the 3973 participants, 410 (10.3%) were infected with C trachomatis. Infected women were significantly younger (22 v 25 years, P<0.0001) and more likely to have symptoms suggestive of a bacterial sexually transmitted infection (53% v 41%, odds ratio 1.63 (95% CI 1.30 to 2.04)), be a contact of someone with a sexually transmitted infection (25% v 5%, odds ratio 6.18 (4.61 to 8.30)), clinically diagnosed with cervicitis (17% v 4%, odds ratio 4.92 (3.50 to 6.91)), and have pelvic inflammatory disease (9% v 3%, odds ratio 2.85 (1.87 to 4.33)). When women co-infected with gonorrhoea were included in the analysis, there was an association with mixed ethnicity (10% v 7%, odds ratio 1.53 (1.07 to 2.17)); but when those with gonorrhoea were removed, women of white ethnicity were significantly more likely to have chlamydia (85% v 80%, odds ratio 1.40 (1.03 to 1.91)). On analysis of complete paired results, vulvovaginal swabs were significantly more sensitive than endocervical swabs (97% (95% CI 95% to 98%) v 88% (85% to 91%), P<0.00001); corresponding specificities were 99.9% and 100%. In women with symptoms suggestive of a bacterial sexually transmitted infection, vulvovaginal swabs were significantly more sensitive than endocervical swabs (97% (93% to 98%) v 88% (83% to 92%), P=0.0008), as they were in women without symptoms (97% (94% to 99%) v 89% (84% to 93%), P=0.002). CONCLUSIONS: Vulvovaginal swabs are significantly better than endocervical swabs at detecting chlamydia in women with and without symptoms suggestive of sexually transmitted infections. In those with symptoms, using endocervical samples rather than vulvovaginal swabs would have missed 9% of infections, or 1 in every 11 cases of chlamydia. TRIAL REGISTRATION: ISRCTN42867448.

Assessment of self taken swabs versus clinician taken swab cultures for diagnosing gonorrhoea in women: single centre, diagnostic accuracy study.

OBJECTIVE: To compare gonorrhoea detection by self taken vulvovaginal swabs (tested with nucleic acid amplification tests) with the culture of urethral and endocervical samples taken by clinicians. DESIGN: Prospective study of diagnostic accuracy. SETTING: 1 sexual health clinic in an urban setting (Leeds Centre for Sexual Health, United Kingdom), between March 2009 and January 2010. PARTICIPANTS: Women aged 16 years or older, attending the clinic for sexually transmitted infection (STI) testing and consenting to perform a vulvovaginal swab themselves before routine examination. During examination, clinicians took urethral and endocervical samples for culture and an endocervical swab for nucleic acid amplification testing. INTERVENTIONS: Urethra and endocervix samples were analysed by gonococcal culture. Vulvovaginal swabs and endocervical swabs were analysed by the Aptima Combo 2 (AC2) assay; positive results from this assay were confirmed with a second nucleic acid amplification test. MAIN OUTCOME MEASURES: Positive confirmation of gonorrhoea. RESULTS: Of 3859 women with complete data and test results, 96 (2.5%) were infected with gonorrhoea (overall test sensitivities: culture 81%, endocervical swabs with AC2 96%, vulvovaginal swabs with AC2 99%). The AC2 assays were more sensitive than culture (P<0.001), but the endocervical and vulvovaginal assays did not differ significantly (P=0.375). Specificity of all Aptima Combo 2 tests was 100%. Of 1625 women who had symptoms suggestive of a bacterial STI, 56 (3.4%) had gonorrhoea (culture 84%, endocervical AC2 100%, vulvovaginal AC2 100%). The AC2 assays were more sensitive than culture (P=0.004), and the endocervical and vulvovaginal assays were equivalent to each other. Of 2234 women who did not have symptoms suggesting a bacterial STI, 40 (1.8%) had gonorrhoea (culture 78%, endocervical AC2 90%, vulvovaginal AC2 98%). The vulvovaginal swab was more sensitive than culture (P=0.008), but there was no difference between the endocervical and vulvovaginal AC2 assays (P=0.375) or between the endocervical AC2 assay and culture (P=0.125). The endocervical swab assay performed less well in women without symptoms of a bacterial STI than in those with symptoms (90% v 100%, P=0.028), whereas the vulvovaginal swab assay performed similarly (98% v 100%, P=0.42). CONCLUSION: Self taken vulvovaginal swabs analysed by nucleic acid amplification tests are significantly more sensitive at detecting gonorrhoea than culture of clinician taken urethral and endocervical samples, and are equivalent to endocervical swabs analysed by nucleic acid amplification tests. Self taken vulvovaginal swabs are the sample of choice in women without symptoms and have the advantage of being non-invasive. In women who need a clinical examination, either a clinician taken or self taken vulvovaginal swab is recommended.