Extraprostatic Lesions Research Articles

PET-CT 18F-PSMA 1007 in the staging of patients with prostate cancer prior to curative intent radiotherapy: a prospective observational study

Objective: The objective of our study was to assess whether there are staging changes in CaP with PET PSMA compared to standard diagnostic methods, and if these changes occurred, to understand how they altered the treatment of patients with an initial diagnosis of CaP and their relationship with the D'amico score. Methods: We present a prospective observational study conducted on patients initially diagnosed with prostate cancer, who underwent standard staging studies alongside PET PSMA imaging. Results: Forty patients diagnosed with prostate cancer were staged using standard diagnostic methods and PET PSMA. In 40% of the patients, initial staging changed based on the results obtained from PET PSMA. After PET PSMA, the uro-oncology committee decided to modify the initial treatment plan in 27.5% of the cases, including radiation boost targeting the extra-prostatic lesions detected by PET PSMA. When correlating the change in staging with PET PSMA versus the D'amico risk score, no changes were observed in the low-risk group, 19% in the intermediate-risk group, and 62% in the high-risk group. These differences were statistically significant (X2=9.2; df=2; p=0.01). Limitation and value: The study faced limitations in sample size and lack of long-term patient follow-up. However, it highlights key contributions: the promising evaluation of PET PSMA in staging, its influence on therapeutic decisions, and its association with the D'amico score. Conclusion: PET PSMA showed substantial changes in CaP staging, particularly in higher-risk patients, suggesting its potential utility in guiding therapeutic decisions before radiotherapy.

PSMA-based PET as an imaging biomarker of androgen receptor signaling in high-risk localized and locally advanced prostate cancer (PCa).

341 Background: The purpose of this prospective, nonrandomized, pilot imaging study (NCT02420977) is to evaluate prostate-specific membrane antigen (PSMA), [18F]DCFPyL (DCFPyL), as a PET/CT imaging biomarker of androgen receptor (AR) signaling in newly diagnosed PCa. Methods: 23 men with treatment-naïve, newly diagnosed high-risk prostate cancer were enrolled. Patients underwent DCFPyL PET/CT imaging and MRI/ultrasound fusion-guided prostate biopsy before and after 2-3 months of nADT (LHRH agonist and anti-androgen), followed by definitive IMRT. We measured the total number of lesions, lesion location, maximum standardized tumor uptake value (SUVmax), PSA, and changes in those variables between baseline and follow-up scans. Concordance between biopsy pathology results and PSMA imaging parameters before and after ADT was evaluated. Results: 3 patients were excluded after baseline PET/CT due to high-burden metastases, small cell histology, and declining to proceed further. 20 patients remained for evaluation. At baseline, 19/20 and 8/20 had at least 1 avid intraprostatic and extraprostatic lesion, respectively, with a 50 total lesions (28 prostate, 19 nodal, 3 bone); median intraprostatic and extraprostatic SUVmax were respectively 9.6 (range: 3.3-56.8) and 7.0 (range: 2.3-61.9). Post-nADT scans revealed 32 lesions (19 prostate, 11 nodes, 2 bone); median intraprostatic and extraprostatic SUVmax decreased respectively to 4.1 (range 1.9-27.8) and 3.2 (range: 1.7-8.9). 3/19 (15.8%) of the patients demonstrated complete uptake resolution of the avid intraprostatic foci, 15/19 (78.9%) showed decreased uptake (58.3% median decrease in SUVmax), and 1/19 (5.26%) showed increased SUVmax. Of the 8 patients with extraprostatic lesions, 2/8 (25%) demonstrated complete uptake resolution, 5/8 (62.5%) showed partially decreased uptake (66.67% median decrease in SUVmax), and 1/8 (12.5%) showed increased SUVmax. One of the same patients still had 2 lesions, for a total of 13 intraprostatic target lesions. Regarding concordance between pathologic results and PSMA imaging response pre- and post-nADT, 14/19 (73%) had biopsies fully concordant with PSMA scan (i.e. residual tumor and residual PET avidity), 4/19 (21%) had biopsies mostly concordant with the scan (i.e. complete pathologic response with partial PET response or vice versa), and 1/19 (5%) had a biopsy discordant with the PSMA scan (i.e. no pathology response, but complete response on PSMA). Conclusions: Post-nADT PET detected fewer PSMA-positive lesions with overall decreased or resolved tumor uptake, except for 2 separate patients with increased intra- and extraprostatic uptake. 95% of post-nADT PSMA scans were fully or mostly concordant with post-nADT biopsies, suggesting that PSMA scans may be a clinically useful, prognostic imaging biomarker for disease status evaluation post-nADT. Clinical trial information: NCT02420977 .

Positivity Rate of [18F]Fluciclovine PET/CT in Patients with Suspected Prostate Cancer Recurrence at PSA Levels Below 1 ng/mL.

Early and precise localization of recurrent prostate cancer lesions after local therapy facilitates optimal disease management. Here, we present results from a single-center study to evaluate the utility of [18F]fluciclovine PET/CT to localize prostate cancer recurrence in patients with PSA <1 ng/mL. Data from men who underwent [18F]fluciclovine PET/CT (August 2016-March 2020) for suspected recurrent prostate cancer and who had a PSA value <1ng/mL were retrospectively reviewed. The number of positive scans (positivity rates, PR) was calculated for the whole body, prostate/bed, and extraprostatic regions (pelvic or extrapelvic lymph nodes, bones, and soft tissue). PR were stratified by pre-scan PSA. Data from 113 patients were included. In total, 98 (87%) were post-prostatectomy and 15 (13%) had received non-surgical primary therapy. Twenty patients (18%) were receiving ADT at the time of the scan, 91 (81%) were not, and ADT status was not known for 2 (1.8%) patients. The overall PR at PSA <1ng/mL was 59% (67/113). For the prostate/bed, it was 35% (40/113), and for extraprostatic locations, it was 37% (42/113). At PSA >0-<0.2, 0.2-<0.5, and 0.5-<1 ng/mL, the overall PR was 43% (10/23), 70% (35/50), and 55% (22/40), respectively. In the prostate/bed, these were 13% (3/23), 50% (25/50), and 30% (12/40), respectively, and in extraprostatic lesions were 30% (7/23), 44% (22/50), and 33% (13/40), respectively. Pelvic lymph nodes were the most common site for extraprostatic lesions (29/113, 26%). PR in extrapelvic lymph nodes, bone, and soft tissue were 8.0%, 12%, and 3.5%, respectively. Soft tissue lesions comprised lung nodules (n=3) and a perirectal mass implant (n=1). Despite low PSA values, more than half of patients had positive [18F]fluciclovine PET/CT findings. Patients with low PSA levels may demonstrate suspicious findings outside of the pelvis, including abdominal lymph nodes and metastatic disease to bones and lungs.

99mTc-PSMA SPECT/CT Versus 68Ga-PSMA PET/CT in the Evaluation of Metastatic Prostate Cancer.

99mTc-prostate-specific membrane antigen (PSMA) SPECT/CT is less expensive and readily available modality compared with 68Ga-PSMA PET/CT for imaging prostate cancer (PC). The aim of this study is to compare the value of these 2 modalities in patients confirmed or suspicious to have metastatic prostate cancer. Twenty-two patients with the mean age of 66.6 ± 10.1 years were studied using 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT, with less than 7 days interval between the 2 imaging procedures. Whole-body PET/CT was done 60 minutes after IV injection of 185 MBq (5 mCi) of 68Ga-PSMA. 99mTc-PSMA SPECT/CT was performed 3 hours after IV injection of 555 to 740 MBq (15-20 mCi) of 99mTc-PSMA. The images of each modality were interpreted independently, and the results were compared according to patient-based as well as region-based analyses. In patient-based evaluation, both 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT scans were positive in 95.45% (21/22). In region-based evaluation, 68Ga-PSMA PET/CT detected 53 regions (median of 2 regions per patient; range, 0-5), whereas 43 (median of 2 regions per patient; range, 0-5) were detected by 99mTc-PSMA SPECT/CT. Most of these differences could be explained by lower detection rate of 99mTc-PSMA SPECT/CT in prostate bed (n = 6). PET/CT detected more involved regions than SPECT/CT (P = 0.007), whereas similar frequency of extraprostatic lesions were diagnosed in both modalities (P = 0.102). Significant correlation was also demonstrated between serum prostate-specific antigen level and imaging parameters of disease extension detected by 2 modalities. 99mTc-PSMA SPECT/CT could be a potential substitute for 68Ga-PSMA PET/CT in high-risk patients, except when evaluation of prostate bed is of major concern.

Prostate cancer recurrence in patients with negative or equivocal conventional imaging: A role for 18F-fluciclovine-PET/CT in delineating sites of recurrence and identifying patients with oligometastatic disease

IntroductionDespite improvements in overall survival, biochemical recurrence of prostate cancer, characterized by rising prostate-specific antigen (PSA) levels after curative intent primary therapy, remains common. With the advent of highly sensitive molecular imaging, men with limited metastatic disease burden, or oligometastatic prostate cancer, are increasingly being identified. The LOCATE trial (NCT02680041) assessed the impact of positron emission tomography (PET) with 18F-fluciclovine on management of men with prostate cancer recurrence after curative intent primary therapy and negative/equivocal conventional imaging. Here, we use LOCATE data to characterize the sites of disease recurrence and explore the potential for 18F-fluciclovine-PET/CT to evaluate oligometastatic disease. MethodsEligible men (≥18 years; prior curative intent treatment of prostate cancer; recurrence based on rising PSA; negative/equivocal conventional imaging) underwent 18F-fluciclovine-PET/CT according to standard protocols. The primary outcome measure of the LOCATE trial was a revised management plan post-scan. We performed a secondary analysis of the LOCATE imaging data to characterize anatomical sites of disease recurrence and to explore the potential for 18F-fluciclovine-PET/CT to evaluate oligometastatic disease. Imaging results were stratified by baseline PSA levels and prior treatment(s) and the Fisher exact test used to analyze differences between groups. Oligometastatic disease was defined as 1–5 extraprostatic lesions (≤3 lesions in any single organ system) plus negative prostate/bed imaging (as a surrogate for primary tumor control). ResultsOf 213 enrolled patients, 164 (77%) had undergone prostatectomy as their initial treatment; their median PSA was 0.57ng/ml. For the 49 patients with an intact prostate, the median PSA was 5.5ng/ml. The overall 18F-fluciclovine-PET/CT detection rate was 57%. Detection rates were 84% in men with intact prostates and 49% in those who had undergone prostatectomy, with the difference being attributable to prostate/bed findings (71% vs. 18%, respectively). The detection rate in lymph nodes was 29% and in bone was 11%. In total, 53/213 (25%) had oligometastatic disease. Twenty (38%) oligometastatic patients had PSA ≤1.0 ng/ml. Forty-two (79%) experienced a change to their management plan following the scan, commonly to target a lesion identified by 18F-fluciclovine-PET/CT. The majority of management changes (74%) involved a new treatment modality; however, 10 patients (24%) experienced a modification of the existing plan for radiotherapy to incorporate a boost to an area guided by the 18F-fluciclovine-PET/CT results. ConclusionEven at low PSA levels, 18F-fluciclovine-PET/CT identified a diverse pattern of recurrence missed with conventional imaging. One-quarter of men had oligometastatic disease, raising the potential for 18F-fluciclovine-PET/CT to guide targeted treatment of oligometastases.

Incremental Value of Ga-68 Prostate-Specific Membrane Antigen-11 Positron-Emission Tomography/Computed Tomography Scan for Preoperative Risk Stratification of Prostate Cancer.

Background:Prostate cancer (PC) is the second-most common cause of cancer.68Ga-prostate-specific membrane antigen (PSMA)-11 positron-emission tomography/computed tomography (PET/CT) scan help in accurate staging of PC owing to its high PSMA avidity and specificity. The aim of this prospective observational study was to determine the incremental value of Ga-68 PSMA-11 PET/CT over multiparametric magnetic resonance imaging (mpMRI) in the locoregional staging of intermediate- and high-risk PC using histopathology from radical prostatectomy specimens as a gold standard.Materials and Methods:This was a prospective study, including 35 patients with biopsy-proven prostate carcinoma. All the patients underwent whole-body Ga-68 PSMA-11 PET/CT scans along with mpMRI including a dedicated pelvic imaging protocol within a time window of ± 10 days. The reference standard was based on histopathological results, postprostatectomy.Results:All 35 patients showed Ga-68 PSMA-11-avid disease, of which 29 underwent radical prostatectomy, one underwent radiation therapy, and five did not undergo surgery owing to metastases. A total of 52 PC lesions were detected in 29 patients on histopathology. Of 52 lesions, 29 lesions were identified in prostate parenchyma and 23 were extraprostatic lesions on histopathology. Ga-68 PSMA-11 PET/CT detected a total of 45 lesions, of which 29 lesions were located within the prostate parenchyma and 16 were representative of extraprostatic lesions. mpMRI detected a total of 36 lesions, of which 29 lesions were located within the prostate parenchyma and seven were representative of extraprostatic lesions. The overall sensitivity of 68Ga-PSMA PET/CT and mpMRI in the detection of lesions was 86.2% and 68.6%, respectively. However, the overall specificity was 94.7% and 89.1% for 68Ga-PSMA and mpMRI, respectively.Conclusion:Ga-68 PSMA-11 PET/CT provided superior locoregional preoperative staging of PC as compared to mpMRI in intermediate- and high-risk PC patients.

Pilot study of dual imaging with 89Zr-IAB2M and 68Ga-PSMA-11 PET/CT prior to prostatectomy.

90 Background: Due to high expression of Prostate Specific Membrane Antigen (PSMA), it’s an excellent candidate for targeted molecular imaging. 89Zr-df-IAB2M is a J591 antibody derived minibody and 68Ga-PSMA-11 is a PSMA small molecule. Methods: Patients with clinically significant (defined as: ≥ 0.5 cm3 with Gleason pattern ≥ 4) localized prostate cancer (PCa) on conventional imaging modalities who planned to undergo surgery were imaged by PET/CT 1-3 hours after 5±2mCi of 68Ga-PSMA-11 injection and 89Zr-IAB2M PET 2-4 days after 10mg IAB2M labeled with 2.5 mCi of 89Zr injection. Image results were interpreted by a central reader without knowledge of the surgical pathology, mapped and the mapped findings later compared with surgical pathology map. Results: 9 patients having clinically localized PCa with median age 65 (46-79) and PSA 8.42 (1.6-12.2) were enrolled. All dominant PCa lesions, which had a median Gleason score 8 (6-9), were detected by both IAB2M and PSMA-11. The smallest of these dominant lesions was 8mm in size. Median SUVmax for dominant lesions was 3.3 (2.3-7.5) on IAB2M and 7.1 (1.6-23.2) on PSMA-11; median MR PIRADS was 4 (4-5). Of 9 Gleason 6 lesions identified on pathology, PSMA-11 detected 3 and IAB2M detected 2. Four extra-prostatic lesions in one patient were detected by both PET agents, 3 were confirmed by surgical pathology and 1 confirmed on bone scan 2 months post-op. A total of 8 lesions reported on scans were not reported by path: 3 were false positive on both scans, 3 were false positive on IAB2M scan only and 2 were false positive on PSMA-11 scan only. 5 Gleason 6 and 2 Gleason 3+4 lesions on pathology were missed by both PET agents and could be considered false negatives. Conclusions: In this small pilot series, performance of the both PET agents was very similar. An advantage of IAB2M is its hepatobiliary clearance rather than renal/urinary, which makes it potentially easier to visualize the PCa and/or pelvic disease; an advantage of PSMA-11 is the ability to image within 1 hour. Clinical trial information: NCT03675451.

Extra-prostatic transgene-associated neoplastic lesions in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.

Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of preneoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubuloacinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here, we describe the histologic and immunohistochemical features of 2 novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice and in male TRAMP mice without histologically apparent prostate tumors. In this article, we also calculate the incidences of the urethral carcinomas and renal tubuloacinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice.