Detection Of Recurrent Prostate Cancer Research Articles

Location of Local Recurrences Post-Prostatectomy Detected by 18F-DCPFyL and Implications for Salvage Radiotherapy Target Volumes.

The use of prostate-specific membrane antigen (PSMA) PET scans have improved detection of recurrent prostate cancer for biochemical failure post-prostatectomy. The primary aim of this study is to assess the location of local recurrences for PSMA PET positive disease post-prostatectomy relative to anatomical landmarks and to inform salvage radiotherapy contouring guidelines. This is a retrospective study of patients who underwent a staging PSMA PET-CT scan with 18F-DCFPyL tracer. Eligible patients included men with biochemical recurrence (PSA >0.2ng/mL) post-prostatectomy for prostate adenocarcinoma. PSMA positive local disease (GTV) was marked on the CT scan of the PSMA PET/CT, using the PSMA PET scan fused as the secondary dataset. Reference structures were contoured to compare the positional relationship to the GTV local recurrence. Centroids of each GTV position were measured to the closest border of the reference structures and distance measured. Forty-five patients had a local recurrence on PSMA PET, 28/45 with prostate bed recurrence and 17/45 with seminal vesicle bed recurrence. The median age was 72.7 years, median pre-treatment PSA 0.515 ng/ml (0.2-11.1), pT2 in 37.8% and pT3 in 62.2, ISUP G2-3 was 66.7%, ISUP 4-5 29.6%, 67% ECE, 15.4% SV involvement and 40% positive margin. For prostate bed recurrences, 93.6% of GTVs were within 15mm from the inferior border of pubic symphysis (median 3.3mm [-9.8-15.4]), 83.9% within 10mm from the VUA (median 3.3mm [-17.4-15.9]), and 80.6% were greater than 10mm from the most superior slice of the penile bulb (median 16.4mm [1-29.5]). Laterally, 83.9% of recurrences were within 10mm of midline and 41.9% within 5mm (median 3.3mm [-13.56-11.59]) and all were contained within levator, 35.5% within 5mm (median 7.7 [1-22.6]) of the medial muscle border. 29.0% were within 5mm from the anterior edge of the rectal wall (median -7mm [-32.3-0.5]). Seminal vesicle bed recurrences were within 17.5mm of upper border of pubic symphysis for 88.9% of patients (median -4.69mm[-30.8to18.2]), 100% were more than 7.5mm inferiorly from the vas deferens (median-22.1mm[-32.7to-7.7]). Laterally, 100% recurrences were more than 7.5mm medial from obturator internus (median 5.37mm [-23.1to37.8]), and 88.9% were more than 10mm from midline (median 23.1mm [2.0-36.6]). The 18F-DCFPyL PSMA PET local recurrences can provide detailed localization of prostate bed and seminal vesicle recurrences. Our data can inform contouring guidelines for salvage radiotherapy to the prostate bed, particularly when using anatomical landmarks to define cranio-caudal extent of target volumes. For target volume laterally, the medial wall of levator ani would encompass all prostate bed recurrences, and no seminal vesicles recurrences were seen at the medial border of the obturator internus muscle.

PSMA-11 PET/CT for Detection of Recurrent Prostate Cancer in Patients With Negative Choline PET/CT.

Prostate adenocarcinoma (CaP) is the leading cancer in men. After curative treatment, from 27% to 53% of patients will experience biochemical recurrence (BR). With the development of focal therapies, precise early identification of recurrence's sites is of utmost importance in order to deliver individualized treatment on positive lesions. The aim of this study was to assess the detection rate (DR) of 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) in selected patients with prostate cancer BR and recent negative 18F-choline PET/CT. We performed a retrospective analysis including all patients with CaP referred for BR with a negative 18F-choline PET/CT, and who underwent 68Ga-PSMA-11 PET/CT between October, 2018 and December, 2019. The overall DR of 68Ga-PSMA-11 PET/CT was calculated, and described according to BR characteristics especially PSA levels and velocity. Patients were followed up for at least 1 year. Patient management following 68Ga-PSMA-11 PET/CT and PSA levels evolution after treatment were also recorded. One hundred fifty-nine patients comprising 164 examinations were analyzed. The overall DR of 68Ga-PSMA-11 PET/CT for BR was 65.9% (95CI, 58.6-73.1). The DR was 52.5% (95CI, 39.9-65.0), 70.6% (95CI, 55.3-85.9), 70.4% (95CI, 53.1-87.6), and 78.6% (95CI, 66.2-91.0) for PSA levels between 0.2 and 0.49 ng/mL, 0.5 to 0.99 ng/mL, 1 to 1.99 ng/mL and PSA ≥ 2 ng/mL, respectively. The DR was 70.7% (95CI, 59.0-82.4) with a PSA doubling time (PSA-DT) ≤6 months and 65.2% (95CI, 55.5-74.9) with a PSA-DT >6 months. Around 3/4 of patients (75.9%) with a positive 68Ga-PSMA-11 PET/CT initiated treatment, including surgery (2.4%), stereotactic radiotherapy ± androgen deprivation therapy (ADT) (22%) or external conformational radiotherapy ± ADT (46.3%). Patient management changed in 43 cases (39.8%). Our study confirmed the ability of 68Ga-PSMA-11 PET/CT to detect occult biochemical recurrence, even in a selected population of CaP patients with negative 18F-choline PET/CT, even at low PSA levels.

Patient-specific forecasting of postradiotherapy prostate-specific antigen kinetics enables early prediction of biochemical relapse

The detection of prostate cancer recurrence after external beam radiotherapy relies on the measurement of a sustained rise of serum prostate-specific antigen (PSA). However, this biochemical relapse may take years to occur, thereby delaying the delivery of a secondary treatment to patients with recurring tumors. To address this issue, we propose to use patient-specific forecasts of PSA dynamics to predict biochemical relapse earlier. Our forecasts are based on a mechanistic model of prostate cancer response to external beam radiotherapy, which is fit to patient-specific PSA data collected during standard posttreatment monitoring. Our results show a remarkable performance of our model in recapitulating the observed changes in PSA and yielding short-term predictions over approximately 1 year (cohort median root mean squared error of 0.10-0.47ng/mL and 0.13 to 1.39ng/mL, respectively). Additionally, we identify 3 model-based biomarkers that enable accurate identification of biochemical relapse (area under the receiver operating characteristic curve>0.80) significantly earlier than standard practice (p<0.01).

Effect of hormonal therapy on 18F-fluciclovine PET/CT in the detection of prostate cancer recurrence, localization of metastatic disease, and correlation with prostate-specific antigen.

18F-Fluciclovine, is a positron emission tomography (PET) radiotracer approved for the localization of sites of prostate cancer recurrence in men with a rising prostate-specific antigen (PSA) after definitive treatment. To explore the impact of androgen deprivation therapy (ADT) on the performance of 18F-fluciclovine, we conducted a retrospective analysis to compare the 18F-fluciclovine PET/CT positivity rate in patients receiving ADT at the time of the scan with the rate achieved in patients not receiving ADT. A retrospective review of data from patients who underwent18F-fluciclovine PET/CT for biochemical recurrence of prostate cancer between December 2016 to March 2020 was performed.The cohort was divided into an ADT group (patient reportedly on ADT) anda non-ADT group (not currently receiving ADT). Patients with unknown ADT status or undetectable/unknown PSA were excluded. For each group, the number of positive18F-fluciclovine PET/CT scans (positivity rate) was evaluated for thewhole body, prostate/bed, and extraprostatic regions and rates were correlated with PSA. The Fisher's Exact test was applied to establish the significancebetween the ADT and non-ADT positivity groups. Mantel-Haenszel trend test was performed to assess linearity between the positivity rate and PSA level. In 320 patients, the status of ADT was known. At the time of the18F-fluciclovine scan,68/320 (21%) patients were on ADT, while 252/320 (79%) were not. The median Gleason score was 8 (range of 6-10) in the ADT group vs. 7 (range of 6-10) in the non-ADT group (P < 0.001). Overall, positivity rates demonstrated no statistical significance between the ADT and non-ADT groups; Positivity rates (ADT vs. non-ADT) were 82% (56/68) vs. 82% (206/252) for the whole body, 57% (39/68) vs. 60% (152/252) for prostate/bed, and 60% (41/68) vs. 53% (133/252) for extraprostatic regions (P > 0.05). A positive linear correlation was noted between PSA and each group's positivity rate (P < 0.01). However, no significant difference was observed between ADT and non-ADT groups at different PSA levels (P > 0.05). Detection of prostate cancer recurrence with 18F-fluciclovine PET/CT is not significantly influenced by ADT, suggesting that localization of disease in patients with detectable PSA who are receiving ADT is feasible with 18F-fluciclovine.

Effect of Androgen Deprivation Therapy on the Results of PET/CT with 18F-Fluciclovine in Patients with Metastatic Prostate Cancer.

Background: 18F-fluciclovine is a positron emission tomography (PET) radiotracer approved for the detection of prostate cancer recurrence. No effect of androgen deprivation therapy (ADT) on its performance has been established. Purpose: To study the impact of concurrent ADT on disease detection with 18F-fluciclovine PET in patients with prostate cancer. Materials and Methods: Data from patients with prostate cancer who had been receiving ADT for ≥3 months at the time of undergoing an 18F-fluciclovine PET/CT at our institution were retrospectively reviewed. Seventy-three scans from 71 patients were included. The scans indicated rising prostate-specific antigen (n = 58), staging advanced disease (n = 4) or therapeutic monitoring (n = 9). Patients’ medical records provided baseline clinical data and post-scan outcomes (median follow-up 40 months). Results: Malignant lesions with increased uptake of 18F-fluciclovine were detected in 60/73 (82%) scans; 33 (45%) had lesions in the prostate/bed and 46 (63%) in extraprostatic sites. Patients received ADT for a median of 2 years (range 3 months to >10 years) pre-scan. The time on ADT did not influence detection; the detection rates were 89% for patients who had received ADT for <1 year, 63% for a treatment period of 1–<2 years, 83% for 2–4 years, 78% for >4–10 years, and 67% for a treatment period of >10 years. Conclusion: 18F-fluciclovine detected recurrent or metastatic lesions in 82% of patients with prostate cancer receiving ADT. The rates achieved in the present study are consistent with widely reported data for 18F-fluciclovine PET/CT, suggesting that withdrawal of ADT before scanning is not necessary.

Testosterone (T) challenge in men post-radical prostatectomy (RP) with profoundly low testosterone

ABSTRACT Introduction Prostate specific antigen is the primary marker of prostate cancer recurrence. PSA secretion is T dependent with T levels below saturation point associated with sub-optimal PSA production. Men with an undetectable PSA level after RP with very low T levels might have an artificially low PSA level. Objective We aimed to evaluate the effects of raising T level in such men. Methods Study population consisted of (i) men post-RP (ii) with undetectable PSA level (iii) total T levels &amp;lt;200 ng/dl (two levels, LCMS) who (iv) underwent in-office intramuscular injection of 100mg of T cypionate (v) had a PSA level checked 5 days later, and if undetectable every month after that, 3 months later then every 6 months and (vi) follow-up of at least 24 months on T therapy. Results 22 men have been challenged thus far. Mean age 62±18 years. Mean preoperative PSA 6.2. Mean post-RP TT value 140± 35 ng/dL 2.2. Median Gleason sum 7. 23% had GS ≥8. Mean post-RP, pre-challenge T value 140± 35 ng/dL. Mean time post-RP to challenge was 7± 9 months. Mean TT value 5 days after IMT challenge 640± 220 ng/dL, all with TT levels above 400. 5/22 has a PSA elevation, 2 immediately after IMT challenge (PSA values 0.07, 0.08). All other men started T therapy immediately and had PSA elevation at 9, 14 and 22 months after commencing T therapy (PSA values 0.08, 0.12, 0.11). All patients with PSA elevation had continued rise in PSA and had detectable disease on imaging. All men with PSA recurrence had either GS 7 with unfavorable pathology (2) or GS ≥8 (3). Conclusions This T challenge approach permits the early detection of prostate cancer recurrence permitting early intervention. About 10% of such men had a PSA rise immediately after T challenge. Disclosure Work supported by industry: no.

Testosterone (T) Challenge in Men Post-Radical Prostatectomy (RP) with Profoundly Low Testosterone

ABSTRACT Introduction Prostate specific antigen is the primary marker of prostate cancer recurrence. PSA secretion is T dependent with T levels below saturation point associated with sub-optimal PSA production. Men with an undetectable PSA level after RP with very low T levels might have an artificially low PSA level. Objective We aimed to evaluate the effects of raising T level in such men. Methods Study population consisted of (i) men post-RP (ii) with undetectable PSA level (iii) total T levels &amp;lt;200 ng/dl (two levels, LCMS) who (iv) underwent in-office intramuscular injection of 100mg of T cypionate (v) had a PSA level checked 5 days later, and if undetectable every month after that, 3 months later then every 6 months and (vi) follow-up of at least 24 months on T therapy. Results 22 men have been challenged thus far. Mean age 62±18 years. Mean preoperative PSA 6.2. Mean post-RP TT value 140± 35 ng/dL 2.2. Median Gleason sum 7. 23% had GS ≥8. Mean post-RP, pre-challenge T value 140± 35 ng/dL. Mean time post-RP to challenge was 7± 9 months. Mean TT value 5 days after IMT challenge 640± 220 ng/dL, all with TT levels above 400. 5/22 has a PSA elevation, 2 immediately after IMT challenge (PSA values 0.07, 0.08). All other men started T therapy immediately and had PSA elevation at 9, 14 and 22 months after commencing T therapy (PSA values 0.08, 0.12, 0.11). All patients with PSA elevation had continued rise in PSA and had detectable disease on imaging. All men with PSA recurrence had either GS 7 with unfavorable pathology (2) or GS ≥8 (3). Conclusions This T challenge approach permits the early detection of prostate cancer recurrence permitting early intervention. About 10% of such men had a PSA rise immediately after T challenge. Disclosure No

18F]Fluciclovine PET/CT Improves the Clinical Management of Early Recurrence Prostate Cancer Patients.

Simple SummaryIn the challenge between increasingly sensitive PET radiopharmaceuticals for the evaluation of prostate cancer patient in biochemical relapse, the choice of the most accurate PET tracer must be guided by literature data, but above all tailored to the patient’s profile. In describing our single-center experience, we aimed to identify biochemical and clinical–histological factors to be considered in patient selection and the semiquantitative parameters that can help the interpretation of malignant from benign lesions, in order to optimize the performance of this imaging method. These data in combination with a significant impact on therapeutic decision making can be useful to further validate the [18F]Fluciclovine PET/CT clinical application.We investigated the [18F]Fluciclovine PET/CT reliability in the early detection of recurrent prostate cancer (PCa) and its impact on therapeutic decision making. We retrospectively analyzed 58 [18F]Fluciclovine PET/CT scans performed to identify early PCa recurrence. Detection rate (DR) and semiquantitative analysis were evaluated in relation to biochemical and clinical–histological features. Clinical follow-up data were collected and considered as gold standard to evaluate sensitivity, specificity, accuracy, positive and negative predictive value (PPV, NPV). The impact of [18F]Fluciclovine PET/CT on clinical management was also assessed. Overall DR resulted as 66%, while DR was 53%, 28%, and 7% in prostate/bed, lymph nodes, and bone, respectively. DR significantly increased with higher PSA values (p = 0.009) and 0.45 ng/mL was identified as the optimal cut-off value. Moreover, SUVmax and SUVmean resulted significant parameters in interpreting malignant from benign findings. [18F]Fluciclovine PET/CT reached a sensitivity, specificity, PPV, NPV, and accuracy of 87.10%, 80.00%, 87.10%, 80.00%, and 84.31%, respectively. Therapeutic strategy was changed in 51% of patients. Our results support [18F]Fluciclovine PET/CT as a reliable tool for early restaging of PCa patients, especially for local recurrence detection, leading to a significant impact on clinical management. Semiquantitative analysis could improve specificity in interpreting malignant from benign lesions.

Comparing the clinical performance and cost efficacy of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 in the diagnosis of recurrent prostate cancer: a Markov chain decision analysis

PurposeAmongst others, [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 are available for the detection of recurrent prostate cancer (rPC). There are currently limited data comparing the performance of these two radioligands with respect to clinical outcomes or their cost efficacy, which this study aims to address.MethodsTwo hundred and forty-four patients undergoing PSMA PET/CT for rPC were retrospectively analysed for this study (one hundred and twenty two with each radiopharmaceutical) to generate rates of PET positivity, negativity and unclear findings. Patients underwent follow-up to determine the rate of additional examinations and to confirm PET findings. A Markov chain decision analysis was implemented to model clinical decision-making processes and to analyse clinical performance of the two tracers. We determine their clinical cost efficacies using cost data from several countries where both radiotracers are in routine use.ResultsThe PET positivity rate was non-significantly higher for [18F]PSMA-1007 compared to [68Ga]Ga-PSMA-11 (91.8% vs. 86.9%, p = 0.68), whereas the rate of uncertain findings was significantly greater (17.2% vs. 8.25%, p = 0.02). The probability of a true positive finding was higher for [68Ga]Ga-PSMA-11 (0.90, 95% CI 0.70-0.98) vs. [18F]PSMA-1007 (0.81, 95% CI 0.66–0.91). A significantly (p < 0.0001) higher PPV for [68Ga]Ga-PSMA-11 (0.99, 95% CI 0.99–1.0 vs. 0.86) was found compared to [18F]PSMA-1007 (0.86, 95% CI 0.82–1.00). Intervention efficacy analysis favoured [68Ga]Ga-PSMA-11, where the number needed to image (to achieve a true positive finding) was 10.58 and the number needed to image to harm (to achieve a false positive finding) was − 8.08. A cost efficacy analysis favours [68Ga]Ga-PSMA-11 in three of the four jurisdictions analysed where health economic data was available (Switzerland, Israel, Australia) and [18F]PSMA-1007 in one jurisdiction (Denmark).ConclusionThe analysis reveals a non-significantly higher PET positivity rate for [18F]PSMA-1007, but finds significantly greater rates of uncertain findings and false positive findings when compared to [68Ga]Ga-PSMA-11. We find differences in the two tracers in terms of clinical performance and cost efficacy. The method presented herein is generalisable and can be used with clinical or cost data for other countries or tracers.

Clinical Application of SPECT-CT Imaging with 99mTc-PSMA in Patients with Recurrent Prostate Cancer

Introduction: Prostate cancer is the most common malignancy in men in Europe. One of the important clinical problems is the early detection and visualization of recurrence after radical prostatectomy, radiation therapy or other radical topical treatment, in patients with PSA values above 0.2 ng/ml. With the introduction of molecular highly sensitive imaging methods after administration of radiolabeled prostate-specific membrane antigen (PSMA), it became possible to detect early functional changes associated with the development of a metastatic process in this disease, with a negative CT or MRI result. 99mTc-PSMA is a new radiopharmaceutical and is a small ligand that binds to the active core of PSMA. The aim of our study was to evaluate the clinical role of 99mTc-PSMA in imaging local recurrence and/or loco-regional and distant metastases in patients with recurrent prostate cancer and biochemical disease progression. Material and methods: A cohort of 36 prostate cancer patients was evaluated with established laboratory data for biochemical progression of the disease - increase in the serum value of the tumor marker PSA and its doubling time within 6 months. In 3/36 of the patients, prostate adenocarcinoma was accidentally detected after transurethral resection of the prostate. Hormonal and cytoreductive radiotherapy was performed in these patients as a therapy. The remaining 33/36 patients underwent radical treatment of primary cancer after a systematic or MRI/US fusion prostate biopsy. Results: All of these patients underwent a whole body scan followed by a targeted SPECT-CT study, 1–3 hours after intravenous administration of 99mTc-PSMA. The sensitivity of the SPECT-CT test with 99mTc-PSMA for the detection of recurrent prostate cancer in 36 followed patients was 84.37% (27/32), specificity - 100% (4/4) and accuracy - 86.11% 31/36). Conclusion: For the clinical application of 99mTc-PSMA SPECT-CT we can summarize that this method finds the greatest clinical application for early diagnosis of recurrent disease in patients with prostate cancer and biochemical progression, at serum PSA levels ≥0.50 ng / ml, in order to determine a personalized treatment for each individual patient. Key words: Prostate cancer, recurrent prostate cancer, 99mTc-PSMA, SPECT-CT

Digital PET and detection of recurrent prostate cancer: what have we gained, and what is still missing?

ABSTRACT Defined by the TIME magazine ‘medical invention of the year 2000,’ positron emission computed tomography (PET/CT) has experienced impressive improvements in technology and clinical applications over time. In recent years, silicon photomultipliers (SiPMs) detectors, characterized by excellent intrinsic time resolution and high photon-detection efficiency, have been introduced as an alternative to the classic photomultiplier tubes (PMTs), thus moving the field of PET technology forward and leading to the so-called digital PET/CT (dPET/CT). On the other side, the radiopharmaceutical 68Ga-PSMA-11, approved by the Food and Drug Administration in December 2020, proved to strongly impact prostate cancer (PCa) diagnosis and management. In the study under evaluation, Alberts et al. retrospectively compared the performance of dPET/CT and PMTs-based PET/CT, namely analogue PET/CT (aPET/CT), in two cohorts, each one including 65 patients undergoing PET/CT with 68Ga-PSMA-11 for suspected recurrent PCa. The authors found that dPET/CT presented a higher detection rate of pathological lesions with respect to aPET/CT. Of note, dPET/CT’s higher sensitivity results are associated with an increased true-positive rate and high inter-reader agreement. This report underscores how innovative PET/CT instrumentation, by utilizing novel radiopharmaceuticals targeting specific metabolic/molecular signatures expressed by PCa, may represent a successful weapon in uro-oncology.

MP36-01 TESTOSTERONE (T) CHALLENGE IN MEN POST-RADICAL PROSTATECTOMY (RP) WITH PROFOUNDLY LOW TESTOSTERONE

You have accessJournal of UrologySexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II (MP36)1 Sep 2021MP36-01 TESTOSTERONE (T) CHALLENGE IN MEN POST-RADICAL PROSTATECTOMY (RP) WITH PROFOUNDLY LOW TESTOSTERONE John P. Mulhall, Serkan Deveci, Jose Flores, Kazuhito Matsushita, Jose Torremade, and Carolyn A. Salter John P. MulhallJohn P. Mulhall More articles by this author , Serkan DeveciSerkan Deveci More articles by this author , Jose FloresJose Flores More articles by this author , Kazuhito MatsushitaKazuhito Matsushita More articles by this author , Jose TorremadeJose Torremade More articles by this author , and Carolyn A. SalterCarolyn A. Salter More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002045.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate specific antigen is the primary marker of prostate cancer recurrence. PSA secretion is T dependent with T levels below saturation point associated with sub-optimal PSA production. Men with an undetectable PSA level after RP with very low T levels might have an artificially low PSA level. We aimed to evaluate the effects of raising T level in such men. METHODS: Study population consisted of (i) men post-RP (ii) with undetectable PSA level (iii) total T levels <200 ng/dl (two levels, LCMS) who (iv) underwent in-office intramuscular injection of 100mg of T cypionate (v) had a PSA level checked 5 days later, and if undetectable every month after that, 3 months later then every 6 months and (vi) follow-up of at least 24 months on T therapy. RESULTS: 22 men have been challenged thus far. Mean age 62±18 years. Mean preoperative PSA 6.2. Mean post-RP TT value 140±35 ng/dL 2.2. Median Gleason sum 7. 23% had GS ≥8. Mean post-RP, pre-challenge T value 140± 35 ng/dL. Mean time post-RP to challenge was 7±9 months. Mean TT value 5 days after IMT challenge 640±220 ng/dL, all with TT levels above 400. 5/22 has a PSA elevation, 2 immediately after IMT challenge (PSA values 0.07, 0.08). All other men started T therapy immediately and had PSA elevation at 9, 14 and 22 months after commencing T therapy (PSA values 0.08, 0.12, 0.11). All patients with PSA elevation had continued rise in PSA and had detectable disease on imaging. All men with PSA recurrence had either GS 7 with unfavorable pathology (2) or GS ≥8 (3). CONCLUSIONS: This T challenge approach permits the early detection of prostate cancer recurrence permitting early intervention. About 10% of such men had a PSA rise immediately after T challenge. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e636-e636 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information John P. Mulhall More articles by this author Serkan Deveci More articles by this author Jose Flores More articles by this author Kazuhito Matsushita More articles by this author Jose Torremade More articles by this author Carolyn A. Salter More articles by this author Expand All Advertisement Loading ...

68Ga-PSMA-11 PET imaging in patients with ongoing androgen deprivation therapy for advanced prostate cancer

PurposeProstate-specific membrane antigen (PSMA) targeted positron emission tomography (PET) imaging significantly improved the detection of recurrent prostate cancer (PCa). However, the value of PSMA PET imaging in patients with advanced hormone-sensitive or hormone-resistant PCa is still largely unknown. The aim of this study was to analyze the detection rate and distribution of lesions using PSMA PET imaging in patients with advanced PCa and ongoing androgen deprivation therapy (ADT).MethodsA total of 84 patients diagnosed with hormone-sensitive or hormone-resistant PCa who underwent 68Ga-PSMA-11 PET/magnetic resonance imaging (MRI) or computer tomography (CT) under ongoing ADT were retrospectively analyzed. We assessed the detection of PSMA-positive lesions overall and for three PSA subgroups (0 to < 1 ng/mL, 1 to < 20 ng/mL and > 20 ng/mL). In addition, PSMA-positive findings were stratified by localization (prostatic fossa, pelvic, para-aortic, mediastinal/supraclavicular and axillary lymph nodes, bone lesions and visceral lesions) and hormone status (hormone-sensitive vs. hormone-resistant). Furthermore, we assessed how many patients would be classified as having oligometastatic disease (≤ 3 lesions) and theoretically qualify for metastasis-directed radiotherapy (MDRT) in a personalized patient management.ResultsWe detected PSMA-positive lesions in 94.0% (79 of 84) of all patients. In the three PSA subgroups detection rates of 85.2% (0 to < 1 ng/mL, n = 27), 97.3% (1 to < 20 ng/mL, n = 37) and 100% (> 20 ng/mL, n = 20) were observed, respectively. PSMA-positive visceral metastases were observed only in patients with a PSA > 1 ng/mL. Detection of PSMA-positive lesions did not significantly differ between patients with hormone-sensitive and hormone-resistant PCa. Oligometastatic PCa was detected in 19 of 84 patients (22.6%). Almost all patients, 94.7% (n = 18) would have been eligible for MDRT.ConclusionsIn this study, we observed an overall very high detection rate of 94% using PSMA PET imaging in patients with advanced PCa and ongoing ADT. Even in a majority of patients with very low PSA values < 1 ng/ml PSMA-positive lesions were found.

Case – Prostate-specific antigen bounce: A pitfall in prostate-specific membrane antigen positron emission tomography/computed tomography interpretation

Prostate-specific antigen (PSA) “bounce,” a transient rise in PSA post-therapy, can happen after either brachytherapy (BT) or external beam radiation therapy (EBRT); however, it is more common in the former case. In general, PSA bounce tends to occur within 2–3 years of treatment, rarely exceeds levels of 2–3 ng/ml above the nadir PSA, and tends to resolve over 6–12 months. Studies have shown that prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has a high sensitivity and specificity for the detection of prostate cancer recurrence and can potentially guide therapy. Because salvage treatment (such as local or systemic salvage) may have associated morbidity, it is important to exclude the possibility of PSA bounce before proceeding with salvage treatment. We describe a case of clinically suspected local failure with initial PSA rise and suspicious PSMA PET/CT finding post-therapy that was actually related to a PSA bounce, emphasizing the need for caution in the evaluation of men where a PSA bounce may be a confounding phenomenon.

18F-fluciclovine PET/CT detection of biochemical recurrent prostate cancer in patients with PSA levels

To establish the detection rate of prostate cancer recurrence following definitive therapy by 18F-fluciclovine PET/computed tomography (CT) in patients with biochemical recurrence (BCR) and prostate-specific antigen (PSA) levels less than 2.00 ng/mL. In this retrospective study, 78 patients with a PSA level of less than 2.00 ng/mL were selected from the 211 patients who underwent at least one 18F-fluciclovine PET/CT scan at our institution for the detection of biochemical recurrent prostate cancer between April 2017 and December 2018. Inherent differences in the characteristics of patients with and without a positive scan were investigated for possible associations using multivariable analysis. One or more positive sites of recurrence were identified in 44 out of 78 patients (56.4%). Patients with a Gleason score between 8 and 10 were more likely to have a positive scan compared to patients with Gleason scores of 6-7 [adjusted odds ratio: 3.53, 95% confidence interval (1.13-10.99), P = 0.03]. No other significant association was found between PSA, T classification, and detection rate. 18F-fluciclovine PET/CT demonstrated a detection rate of 56.4% among patients with a PSA below 2.0 ng/mL. The results of this study support the use of 18F-fluciclovine PET/CT for the detection of recurrent prostate cancer at lower PSA levels, even at PSA levels less than 0.5 ng/mL.

Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis

PurposeMany radiotracers are currently available for the detection of recurrent prostate cancer (rPC), yet many have not been compared head-to-head in comparative imaging studies. There is therefore an unmet need for evidence synthesis to guide evidence-based decisions in the selection of radiotracers. The objective of this study was therefore to assess the detection rate of various radiotracers for the rPC.MethodsThe PUBMED, EMBASE, and the EU and NIH trials databases were searched without date or language restriction for comparative imaging tracers for 13 radiotracers of principal interest. Key search terms included 18F-PSMA-1007, 18F-DCPFyl, 68Ga-PSMA-11, 18F-PSMA-11, 68Ga-PSMA-I&T, 68Ga-THP-PSMA, 64Cu-PSMA-617, 18F-JK-PSMA-7, 18F-Fluciclovine, 18F-FABC, 18F-Choline, 11C-Choline, and 68Ga-RM2. Studies reporting comparative imaging data in humans in rPC were selected. Single armed studies and matched pair analyses were excluded. Twelve studies with eight radiotracers were eligible for inclusion. Two independent reviewers screened all studies (using the PRISMA-NMA statement) for inclusion criteria, extracted data, and assessed risk of bias (using the QUADAS-2 tool). A network meta-analysis was performed using Markov-Chain Monte Carlo Bayesian analysis to obtain estimated detection rate odds ratios for each tracer combination.ResultsA majority of studies were judged to be at risk of publication bias. With the exception of 18F-PSMA-1007, little difference in terms of detection rate was revealed between the three most commonly used PSMA-radiotracers (68Ga-PSMA-11, 18F-PSMA-1007, 18F-DCFPyl), which in turn showed clear superiority to choline and fluciclovine using the derived network.ConclusionDifferences in patient-level detection rates were observed between PSMA- and choline-radiotracers. However, there is currently insufficient evidence to favour one of the four routinely used PSMA-radioligands (PSMA-11, PSMA-1007, PSMA-I&T, and DCFPyl) over another owing to the limited evidence base and risk of publication bias revealed by our systematic review. A further limitation was lack of reporting on diagnostic accuracy, which might favour radiotracers with low specificity in an analysis restricted only to detection rate. The NMA derived can be used to inform the design of future clinical trials and highlight areas where current evidence is weak.

Patterns of Recurrence, Detection Rates, and Impact of 18-F Fluciclovine PET/CT on the Management of Men With Recurrent Prostate Cancer

To evaluate the characteristics of FACBC PET/CT in detecting recurrent prostate cancer after radiation or prostatectomy. The secondary aim was to determine the impact of FACBC PET/CT on radiation treatment recommendations in men with biochemical recurrence postprostatectomy. This is a single center retrospective study of men who underwent an FACBC PET/CT for rising PSA after definitive prostate cancer therapy. Detection rates in men with recurrence following any definitive treatment were compared at different PSA levels and anatomical sites. Radiotherapy treatment recommendations for patients postprostatectomy based on conventional imaging findings were compared to recommendations based on FACBC PET/CT findings. A total of 103 men underwent imaging with FACBC PET/CT. 74.8% (77) had lesions consistent with sites of prostate cancer recurrence. At PSA thresholds of <1, 1-2, and >2 ng/mL lesions were detected in 35.5%, 63.6%, and 95.2% of patients respectively (P <.001). The most common site of recurrence was outside of the pelvis (37). Detection of extraprostatic or extrapelvic recurrence was observed in 45.5% of men in the PSA tertile <1ng/mL. FACBC PET/CT results led to changes to the recommended radiotherapy treatment plan in 44.1% (15/34) of men with recurrence following radical prostatectomy. FACBC PET/CT demonstrated increased detection of recurrent prostate cancer with increasing PSA levels. Most recurrences were found outside the pelvis. Results of FACBC PET/CT changed radiotherapy management decisions in men treated with prostatectomy, supporting its use in localizing sites of disease recurrence in men with prostate cancer.

Single Institution Patterns of Management of (18)F-Fluciclovine-detected Prostate Cancer Recurrences

Multiple prostate-cancer directed positron emission tomography (PET) radiotracers have emerged and (18)F-fluciclovine (Axumin) is the most recent agent that has been approved by the US Food and Drug Administration for detection of recurrent prostate cancer (PCa). We report the treatments and outcomes of patients at our institution who had Axumin PET-detected PCa recurrences. We retrospectively identified men with PCa who underwent Axumin PET (Ax-PET) between 2017 and 2018 focusing on men with nonmetastatic PCa previously treated with either surgical resection ± radiation (RT) or definitive RT ± androgen deprivation therapy (ADT). Of these patients, those with recurrent PCa seen on Ax-PET were analyzed for patterns of care and PCa related outcomes. We identified 27 men with nonmetastatic PCa who had recurrent PCa detected on Ax-PET. Twenty-three were initially treated with surgery (median Gleason score 7, median PSA 9.76ng/mL) Of the 23 surgical patients, 17 pathologic node negative patients had indication for postoperative radiation (PORT). 10 men received PORT (5 adjuvant, 5 salvage), 3 with concurrent ADT. The median dose of PORT was 66Gy to the prostate fossa. Four patients were initially treated with definitive RT (2 with ADT) to median dose 76Gy to prostate ± seminal vesicles (median Gleason score 6.5, median PSA 10.1ng/mL). In the surgical patients, the median time to Ax-PET was 67 months with a median PSA of 1.63ng/mL. In the patients initially treated with RT, the median time to Ax-PET was 73 months with median PSA of 2.74ng/ml. In all patients, median time to Ax-PET was 73 months with median PSA 2 (range 0.16-94.18). Seven men recurred in the prostate bed and lymph nodes (median PSA 4.2), 18 recurred in lymph nodes alone (median PSA 0.95), three recurred in lymph nodes and bone (median PSA 46.88ng/mL), and one recurred in bone only (PSA 59.17). Median size of Ax-PET avid lymph nodes was 0.8mm. After Ax-PET, three patients were treated with surgery alone with pathologic correlation in 2/3 patients. Median postoperative PSA declined from 0.84 to 0.13ng/mL. Seven patients were treated with RT (3 with concurrent ADT) with median PSA decline from 0.8 to 0.07ng/mL. Eleven patients were treated with ADT alone with median PSA decline from 4.11 to 2.83ng/mL. Eight patients received no further treatment after Ax-PET. (18)F-Fluciclovine Axumin PET can localize prostate cancer recurrences in the prostate bed, regional lymph nodes, or bone. Focal treatment with surgery or radiation appears effective with decreasing PSA. Longer follow-up is required to see if these diagnostic tests and subsequent therapy will lead to increased prostate cancer specific survival.

Incidental Detection of Lung Adenocarcinoma Presenting as an Anterior Mediastinal Mass on 18F-Fluciclovine PET/CT in a Patient With Primary Prostate Cancer

F-fluciclovine is a PET radiotracer approved for detection of recurrent prostate cancer, with utility in other malignancies being investigated. We present the case of a 71-year-old man with high-risk primary prostate cancer (Gleason score 9, prostate-specific antigen 34 ng/mL) and newly diagnosed lung adenocarcinoma. As part of a clinical trial (NCT03081884), preoperative F-fluciclovine PET/CT showed localized abnormal uptake in the prostate gland with extracapsular extension. Additionally, an incidental anterior mediastinal mass measuring 2.2 × 1.8 cm demonstrated abnormal radiotracer uptake. Biopsy of the mediastinal mass confirmed invasive lung adenocarcinoma with solid and acinar patterns and high programmed death 1 ligand expression.

Deep learning detection of prostate cancer recurrence with 18F-FACBC (fluciclovine, Axumin®) positron emission tomography.

To evaluate the performance of deep learning (DL) classifiers in discriminating normal and abnormal 18F-FACBC (fluciclovine, Axumin®) PET scans based on the presence of tumor recurrence and/or metastases in patients with prostate cancer (PC) and biochemical recurrence (BCR). A total of 251 consecutive 18F-fluciclovine PET scans were acquired between September 2017 and June 2019 in 233 PC patients with BCR (18 patients had 2 scans). PET images were labeled as normal or abnormal using clinical reports as the ground truth. Convolutional neural network (CNN) models were trained using two different architectures, a 2D-CNN (ResNet-50) using single slices (slice-based approach) and the same 2D-CNN and a 3D-CNN (ResNet-14) using a hundred slices per PET image (case-based approach). Models' performances were evaluated on independent test datasets. For the 2D-CNN slice-based approach, 6800 and 536 slices were used for training and test datasets, respectively. The sensitivity and specificity of this model were 90.7% and 95.1%, and the area under the curve (AUC) of receiver operating characteristic curve was 0.971 (p < 0.001). For the case-based approaches using both 2D-CNN and 3D-CNN architectures, a training dataset of 100 images and a test dataset of 28 images were randomly allocated. The sensitivity, specificity, and AUC to discriminate abnormal images by the 2D-CNN and 3D-CNN case-based approaches were 85.7%, 71.4%, and 0.750 (p = 0.013) and 71.4%, 71.4%, and 0.699 (p = 0.053), respectively. DL accurately classifies abnormal 18F-fluciclovine PET images of the pelvis in patients with BCR of PC. A DL classifier using single slice prediction had superior performance over case-based prediction.