METHOD: We carry out an observational study where reviewed the PET/CT studies with PSMA marked with Fluor-18 ( 18F) carried out from February 2019 to September 2020. We analyzed the average value of hepatic uptake SUV lean average (SUVlave), acquisition time, age, reason from the study, focal, multifocal and diffuse prostate uptake, analysis of the location of metastases, level of prostate specific antigen (PSA), we describe uptakes of non-prostate origin and focal uptakes in ribs without anatomical representation. RESULTS: The average hepatic SUVlave was 9.7, the acquisition times were variable (52 - 183 minutes) without alterations in the white-background relationship, the most frequent indication for the study was staging, the uptake in ribs without anatomical representation were considered benign with certain characteristics, PET/CT has the ability to detect neoplastic activity with low PSA levels in lymph nodes < 5 mm and bone metastatic status. CONCLUSION: PET/CT with 18F-PSMA has advantages over bone scan and computed tomography of the abdomen and pelvis for the staging of prostate cancer.
Prostate cancer is a malignant neoplasm that occurs in older men [
Risk factors include age, since most of the prostate cancer diagnosis appears in men over 64 years of age, first-degree family history, black African-American race, and a high-fat diet [
The diagnosis is determined by the prostate specific antigen (PSA), the Gleason score and the extent of the tumor. Various imaging methods are used for initial staging. Magnetic resonance imaging (MRI) shows promising results in locating the tumor and improves the precision of ultrasound-guided biopsy [
Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein type II, encoded in the follolate hydrosylase 1 gene, also known as the transmembrane glutamate II gene [
The physiological biodistribution of 68Ga-PSMA occurs in the lacrimal, salivary glands, small intestine, liver, spleen and in the proximal tubule of the kidney; there is also a significant accumulation of the radiotracer in the ureters and in the bladder due to renal excretion [
Initial staging in high-risk patients due to the fact that in patients with intermediate or high risk prostate cancer, the metastatic nodes may be smaller than 8 mm, the imaging methods (MRI and CT) continue to be of low sensitivity, since they only evaluate size [
Primary tumor:
● Tx: The presence of the primary tumor cannot be assessed.
● T0: There is no evidence of a primary tumor.
● T1: Clinically inapparent tumor (not palpable or visible by imaging techniques).
● T2: Tumor confined to the prostate.
● T3: Tumor that extends beyond the prostatic capsule.
● T4: The tumor invades adjacent organs other than the seminal vesicles.
Lymph node Involvement:
● Nx: Lymph node involvement cannot be assessed.
● N0: Absence of lymph node involvement
● N1: Regional node metastases.
Distant metastasis:
● Mx: The existence of distant metastases cannot be assessed.
● M0: Absence of distant metastasis.
● M1: Distant metastasis (
Bone metastases are among the main causes of pain and death in patients with prostate cancer, the degree of bone involvement is essential to define the best treatment strategy [
PET/CT with PSMA shows potential for the detection of bone metastases in patients with prostate cancer, positron emission tomography has shown superiority over bone scintigraphy to determine a generalized condition [
The expression of PSMA is found in both malignant and benign non-prostatic
pathologies, this situation determines difficulties in interpretation [
● Review of the initial experience in the use of PET/CT with 18F-PSMA.
● Average value of hepatic uptake SUV Lean average (SUVlave).
● Age.
● Analysis of the location of metastases.
● Describe and divide the uptakes of non-prostatic tumors and the focal uptakes in the rib without anatomical representation with 18F-PSMA.
● Determine the relationship between the level of prostate specific antigen (PSA) and positive uptakes for prostate cancer, by PET/CT with 18F-PSMA.
● Reason for the study.
● Focal, multifocal or diffuse prostate.
● APE level.
In February 2019, we started the use of PET/CT with 18F-PSMA, this work will allow us to show our initial experience with this radiopharmaceutical, observe the spread of prostate cancer, and document uptakes of non-prostatic origin.
A retrospective analysis was performed, in which patients undergoing PET/CT with 18F-PSMA from February 2019 to September 2020 were studied at the CT Scanner San Ángel, Mexico City.
Inclusion criteria: patients with PET/CT study with 18F-PSMA and complete file.
Exclusion criteria: patients with an incomplete file.
A total of 393 studies were conducted, 21 patients were excluded due to incomplete records. In total, 372 studies in 252 patients were analyzed.
The patients signed informed consent to carry out the study.
Definition of variables and measurement scales (
In the age analysis, we observed that the average was 70.2 years, median 70 and a mode of 73 years. The youngest patient was 42 years old and the oldest patient was 93 (
VARIABLE | CONCEPTUAL DEFINITION | OPERATIONAL DEFINITION | TYPE OF VARIABLE |
---|---|---|---|
Average liver uptake value (SUV Lean average). | Used to compare the standardized value of uptake with lesions. | It is obtained by placing an VOI in the right lobe of the liver, this used as a reference value. | Quantitative |
Age Independent of the presentation of prostate cancer. | Age Years completed at the time of diagnosis. | It is obtained by ordering the patients by age group. | Quantitative |
Reason for the indication of the study. | Valid Reason for Using the 18F-PSMA Diagnostic Test | It is obtained from patient records. | Quantitative |
Focal, multifocal, or diffuse prostatic uptake. | Location of the primary tumor (right or left lobe or both) | Based on the record obtained from the nuclear medicine report. | Quantitative |
---|---|---|---|
PET/CT studies, positive, negative. | Case numbers. | Based on the records obtained in the database. | Quantitative |
APE level. | A protein produced by the cells of the prostate glands, its concentration in the blood is measured. | The results were obtained from the files. | Quantitative |
Analysis based on the location of metastases. | Spread of prostate cancer to lymph nodes and organs. | Based on the PET/CT results, the anatomical location of the metastases was determined. | Quantitative |
Non-prostatic tumor uptakes. | Standardized value of uptake in lesions of non-prostate origin with 18F-PSMA | Based on the record obtained from the nuclear medicine report | Qualitative |
Focal uptakes in rib. | Standardized uptake value in ribs without anatomical representation. | Based on uptake rib focal only and determined predicter factors. | Qualitative |
Ages grouped by ranges | Number of studies |
---|---|
42 to 51 | 12 |
52 to 61 | 71 |
62 to 73 | 134 |
74 to 82 | 117 |
83 to 93 | 38 |
Total | 372 |
Mean age = 70 age. Standard deviation = 57.47.
In all the studies, we measured the SUVlave at the level of the right liver lobe, finding that the highest value was 21.0, the lowest was 1.1, the average was 9.7, the mode was 10.5 and the median was 9.7.
We also analyzed the post-injection acquisition time of each of the studies performed, the maximum time was 183 minutes, the minimum time was 54 minutes, an average of 86.5 minutes, a median of 83 and a mode of 63 minutes.
The results of the PET/CT with 18F-PSMA were the following: 281 were positive, 87 negative and 4 doubtful.
The prostate uptakes and the distribution of metastases were analyzed, the results were as follows.
Lesion exclusively in the prostate and surgical bed: 81 studies (28.8%) divided into unifocal (30), multifocal (31) and diffuse (20) lesions. Surgical bed with 18 (6.4%).
The highest SUVlmax was 41.1 and the lowest SUVlmax was 2.7 in injuries exclusively to the prostate.
In the surgical bed, the highest SUVlmax was 40.1 and the lowest was 2.7.
Exclusively lymph nodes: 13 (4.6%) studies, in which we found the following:
● 9 Studies with local nodes.
● 1 Study with local + retroperitoneal ganglia.
● 1 Study with local + retroperitoneal + mediastinal nodes.
● 1 Study with local + retroperitoneal + mediastinal + left cervical lymph nodes.
● 1 Study with retroperitoneal + mediastinal lymph nodes.
Exclusively bone metastases: 9 studies (3.2%):
● 1 Study with a single osteoblastic lesion.
● 5 Studies with multiple osteoblastic lesions.
● Studies with multiple lesions without anatomical representation.
Prostate + lymph nodes: 54 (19.2%) studies:
Unifocal: 21 studies:
● 14 Local node studies.
● 5 Local node studies + retroperitoneal.
● 1 Study with retroperitoneal ganglia.
● 1 Study with mediastinal lymph nodes.
Multifocal: 15 studies:
● 7 Local node studies.
● 5 Studies with local + retroperitoneal nodes.
● 2 Studies with local + mediastinal nodes.
● 1 Study with mediastinal lymph nodes.
Diffuse: 18 Studies:
● 10 Local node studies.
● 3 Studies with local + retroperitoneal lymph nodes.
● 1 Study with bilateral retroperitoneal + mediastinal + axillary nodes.
● 2 Studies with retroperitoneal nodes.
● 1 Study with local + retroperitoneal + bilateral cervical nodes.
● 1 Study with local + retroperitoneal + mediastinal + left cervical nodes.
Prostate + bone metastasis: 10 studies (3.55%).
Unifocal: 5 studies:
● 3 Studies with multiple osteoblastic lesions.
● 1 Study with a single metastatic lesion without anatomical representation.
● 1 Study with single osteoblastic lesion.
Multifocal: 4 studies:
● 2 Studies with multiple osteoblastic lesions.
● 1 Study with a single lesion without anatomical representation.
● 1 Study with a single osteolytic lesion.
Diffuse: 1 Study with multiple bone lesion without anatomical representation.
Prostate + lymph nodes + bone metastases: 53 (18.86%) studies.
Unifocal: 17 studies:
● 4 Studies with local lymph nodes + single osteoblastic lesion.
● 3 Studies with local ganglia + multiple osteoblastic lesions.
● 6 Studies with local + retroperitoneal ganglia + multiple osteoblastic lesions.
● 1 Study with local + retroperitoneal ganglia + multiple osteoblastic lesions.
● 1 Study with local lymph nodes + single bone lesion without anatomical representation.
● 1 Study with local + retroperitoneal + mediastinal nodes + single osteoblastic lesion.
● 1 Study with local lymph nodes + left cervical + multiple osteoblastic lesions.
Multifocal: 17 studies:
● 6 With local ganglia + multiple osteoblastic lesions.
● 2 With local lymph nodes + single blastic lesion.
● 1 With local lymph + retroperitoneal + left cervical ganglia + multiple osteoblastic lesions.
● 1 With local lymph + retroperitoneal ganglia + multiple lytic bone lesions.
● 1 With local ganglia + multiple bone lesions without anatomical representation.
● 1 With local nodes + single lytic bone lesion.
● 1 With local retroperitoneal ganglia + single osteoblastic lesion.
● 2 With local nodes + retroperitoneal ganglia + single osteoblastic lesion.
● 1 With local + retroperitoneal ganglia + multiple osteoblastic lesions.
● 1 With local retroperitoneal ganglia + mediastinal + left cervical ganglia and multiple osteoblastic lesions.
Diffuse: 18 studies:
● 2 Studies with local retroperitoneal lymph nodes + single osteoblastic lesion.
● 2 Studies with local ganglia + single lesion without anatomic representation.
● 4 Studies with local lymph node studies + multiple osteoblastic lesions.
● 1 Study with local + retroperitoneal ganglia + single osteoblastic lesion.
● 1 Study with local ganglia + retroperitoneal + mediastinal + multiple osteoblastic nodes.
● 1 Study with local ganglia + retroperitoneal + mediastinal ganglia + multiple osteoblastic and lithic lesions.
● 1 Study with local ganglia + retroperitoneal + multiple bone lesions without anatomical representation.
● 2 Studies with local retroperitoneal nodes + multiple osteoblastic lesions.
● 1 Study with mediastinal lymph nodes + multiple osteoblastic lesions.
● 2 Studies with local lymph nodes + multiple bone lesions without anatomical representation.
● 1 Study with local ganglia + multiple osteolytic lesions.
● 1 Study with local retroperitoneal ganglia + left cervical + multiple bone lesions without anatomical representation.
Ganglion + bone metastasis: 19 studies:
● 1 Study with local lymph nodes + pulmonary hilum + multiple osteolytic lesions.
● 2 Studies with mediastinal lymph nodes + multiple osteoblastic lesions.
● 1 Study with local lymph nodes + multiple osteoblastic lesions.
● 1 Study with local + retroperitoneal + left cervical ganglia + multiple osteolytic lesions without anatomical representation.
● 1 Study with local + retroperitoneal + mediastinal nodes + left pulmonary hilum, left cervical + multiple osteoblastic lesions.
● 2 Studies with local lymph nodes + single osteolytic lesion.
● 1 Study with local + retroperitoneal ganglia + multiple osteoblastic lesions.
● 1 Study with retroperitoneal + mediastinal lymph nodes + multiple osteoblastic and lytic lesions.
● 1 Study with retroperitoneal + mediastinal ganglia + multiple osteoblastic lesions.
● 2 Studies with retroperitoneal lymph nodes + multiple osteoblastic lesions.
● 1 Study with local + retroperitoneal + mediastinal ganglia + multiple osteoblastic and lytic lesions.
● 1 Study with local ganglia + multiple osteoblastic lesions.
● 1 Study with local lymph nodes + retroperitoneal + mediastinal + bilateral cervical nodes + multiple osteoblastic lesions.
● 1 Study with retroperitoneal ganglia + left cervical + multiple osteolytic lesions.
● 1 Study with retroperitoneal ganglia + mediastinal + multiple osteoblastic lesions.
● 1 Study of mediastinal lymph nodes + multiple osteoblastic lesions.
Surgical bed + lymph node: 10 studies (3.55%):
● 8 Local node studies.
● 1 Studies with local + retroperitoneal lymph nodes.
● 1 Study with local + retroperitoneal + left cervical lymph nodes.
Surgical bed + Bone metastases: 5 (1.77%): With multiple osteoblastic lesions.
Surgical bed + lymph nodes + bone metastases: 9 studies (3.2%):
● 1 Study with local + retroperitoneal lymph nodes + single lesion without anatomical representation.
● 1 Study with local + retroperitoneal ganglia and multiple bone lesions without anatomical representation.
● 1 Study with left retroperitoneal + mediastinal + cervical ganglia and single osteoblastic lesions.
● 1 Study with local ganglia + multiple osteoblastic lesions.
● 2 Studies with local + retroperitoneal ganglia + multiple osteoblastic lesions.
● 1 Study with local lymph nodes + single osteoblastic lesion.
● 1 Study with local ganglia + cervical + multiple bone lesions without anatomical representation.
● 1 Study with local retroperitoneal ganglia + multiple osteoblastic and lytic bone lesions (
37 (13.16%) had positive nodes smaller than 5 mm.
27 (9.60%) studies with lymphadenopathy in 38 supradiaphragmatic regions: 12 left cervical nodes, 1 bilateral cervical, 21 mediastinal lymph nodes, 3 in pulmonary hilum and 1 bilateral axillary.
We detected 16 (5.69%) studies with unusual metastases: 7 pulmonary, 3 hepatics, 3 in the penis, 1 splenic, 1 muscular and 1 in the mesorectum (
Of the 393 studies carried out, we have PSA levels in 181 (45.93%). The minimum PSA value was 0.001 and the highest value was 1789 ng/ml (
The reasons for the studies were varied, with staging (144), re-staging (104), assessment of response to treatment (53), surveillance (53) and recurrence (18).
95 studies (25.5%) with uptake of non-prostatic origin with 18F-PSMA, which we divided into three groups, benign 59 (63%), malignant 9 (9%) and nonspecific 27 (28%) (
9.6% of the studies (36) presented focal uptakes of the radiopharmaceutical in ribs but without anatomical representation, we have classified them as nonspecific. In the SUVlmax analysis, the highest was 8.2 and the lowest was 1.8 (average of 4.0 and mode of 2.6) (
PSA ng/ml | PET+ | PET− | PET UNCERTAIN |
---|---|---|---|
0.001 to 0.01 | 6 | ||
>0.01 to ≤0.07 | 2 | 11 | 1 |
≥0.1 to ≤0.5 | 10 | 11 | |
>0.5 to ≤1 | 6 | 1 | |
>1 to ≤5 | 32 | 1 | 1 |
>5 to ≤10 | 37 | 1 | 2 |
>10 to ≤15 | 17 | 1 | |
>15 to ≤20 | 7 | ||
>20 | 34 | ||
Total | 145 | 32 | 4 |
Benign | Number of studies | Malignant | Number of studies | Unspecific | Number of studies |
---|---|---|---|---|---|
Osteodegenerative | 19 | Urothelial origin | 3 | Diffuse thyroid uptake | 11 |
Pulmonary nodules | 3 | Hepatocarcinoma | 1 | Linear in lung | 1 |
Pulmonary infiltrates | 4 | Lymphoma | 1 | Thickening of the rectum | 1 |
Lung consolidation | 1 | Pancreatic neoplasia | 2 | Bladder wall | 1 |
Hemangiomas | 4 | Lung primary | 1 | Nonspecific osseous | 6 |
Inflammatory esophagus | 5 | Liposarcoma in pancreas | 1 | Rib with lytic area | 1 |
Enchondroma | 1 | Iliac nodes | 1 | ||
Epididymis | 1 | Penis | 2 | ||
Fractures | 3 | Inguinal ring | 1 | ||
Atrial lipoma | 1 | Intestinal polyp | 1 |
Meningioma | 1 | Inguinal canal cyst | 1 | ||
---|---|---|---|---|---|
Paget’s disease | 2 | ||||
Fibrocicatricial changes in the lung | 2 | ||||
Thymoma | 1 | ||||
Muscular | 1 | ||||
Adrenal adenoma | 1 | ||||
Thyroid nodule | 1 | ||||
Bladder wall | 1 | ||||
Pleura | 1 | ||||
Bladder wall | 1 | ||||
Lymph nodes (axillary, mediastinal and cervical) | 5 |
Prostate cancer is the second malignant tumor and the second most frequent cause of death in men, PET/CT with 18F-PSMA has proven to be a fundamental non-invasive technique in the initial staging in high-risk patients, important in the planning of the surgical approach, functional in the planning of radiotherapy, location of the tumor in biochemical recurrence, useful as a guide for biopsy in patients with high suspicion of cancer with negative previous biopsy results, and to assess the response to treatment.
The objective of this study is to evaluate the results obtained in the scans carried out with PET/CT with 18F-PSMA during the period: February 2019 to September 2020.
We measured the SUVlave (SUVLean average) in the liver of each one, the highest value found was 21 and the lowest was 1.1, this last value corresponds to a patient with extensive tumor burden (superscan), we found a mode of 10.5 and an average of 9.7. The liver belongs to the physiological uptake of 18F-PSMA, when placing this reference ROI in the liver, verify that the gallbladder is not included.
The acquisition time of most studies (mode) was 63 minutes. 183 minutes the longest and the shortest at 54 minutes. Although the acquisition times were variable, the analyzes have an appropriate quality, with no alterations in the white background relationship.
The average age was 70.2 years, with a mode of 73 years, 124 patients are in the range of 62 to 73 years, our youngest patient with 42 years and our oldest patient 93 years. Our result agrees with the referenced literature, where age is recognized as a risk factor, since most of the prostate cancer diagnosis appears in men older than 64 years.
In the positive PET/CT, the most frequent involvement was observed in lesion exclusively in the prostate with 29.7% (82) with a predominance of multifocal lesions; second, involvement of the prostate + lymph nodes + bone lesions with 21.2% (58) studies.
Surgical bed + bone metastases and surgical bed + lymph nodes were the least frequent with 8 and 10 studies respectively.
37 studies (13.4%) presented nodes smaller than 5 mm with radiopharmaceutical uptake.
As unusual findings, we found 7 pulmonary metastases, 3 liver, 3 in the penis, 1 splenic, 1 of axillary lymphadenopathy, 8 cervical on the left side and 1 bilateral, 1 nodular lesion in the mesorectum and 1 study in a muscle implant.
Despite the high incidence of prostate cancer, there are few reports of metastatic involvement of the cervical nodes, the predilection for the left side is due to the fact that tumor cells can lodge in the nodes by retrograde spread, due to the proximity of the duct thoracic with left subclavian vein [
Hepatic metastases are considered the third site of extra nodal metastases in prostate cancer, after bone and lung; occur in disease refractory to hormonal treatment and in late stages, PSMA uptake in liver metastases may be due to the diversity of prostate cancer phenotypes, predominantly neuroendocrine transdifferentiation [
Most of the reasons for the request were staging with 144 studies.
Of the PET/CT performed we have the PSA value in 179. 18 positive studies with PSA < 1.0, of which the minimum value with positive PET/CT was 0.01 ng/ml.
We documented 89 studies with 18F-PSMA uptake of non-prostatic origin with a predominance in lesions of benign etiology, being the osteodegenerative changes the ones that occurred more frequently, the highest SUVlmax value was 8.5 and the lowest 2.6. Regarding uptakes of non-prostate malignant origin, we present 9 documented studies that present a second primary tumor. In the literature, the association of these uptakes with endothelial neovasculature is well known, showing that PSMA is not exclusive to prostate tissue, this must be taken with relevance, since they can simulate prostate cancer metastasis.
36 studies presented focal uptakes in rib(s) without anatomical representation. In our initial experience, we considered these uptakes as nonspecific, however there was no significant change in size and SUVlmax at follow-up. There is little literature that mentions the nature of these solitary uptake in ribs, however we identified that most of them are of benign origin; taking into account the low uptake of the radiopharmaceutical, the correlation with any signs of trauma and PSA levels [
● The acquisition times were varied, from 54 to 183 minutes, all studies have adequate quality for interpretation without alterations in the white-background relationship.
● The average hepatic SUVlave is 9.7.
● Staging occupied the highest percentage of PET/CT indication.
● We detected both unifocal and multifocal uptakes in the prostate with PET/CT with 18F-PSMA.
● There are uptakes in both benign and malignant lesions due to its expression in the endothelial cells of the neovasculature, that can cause false positives, it is advisable for the doctor who examines the study to have this knowledge in order to obtain an accurate interpretation. There is little literature on solitary uptakes in ribs without anatomical representation with 68Ga-PSMA. To our best knowledge, this is the first study with 18F-PSMA to evaluate and describe uptakes at the rib level. Our results indicate that these findings are considered benign, when PSA levels and the rest of the study are negative.
● Although there is literature that mentions that liver metastases are not so uncommon (25%, 8%) [
● PET/CT with PSMA has the ability to determine bone metastatic status, there are even hyper-uptake bone metastases that we can detect without anatomical representation. We found 11 studies (3.91%) with hyper-uptake lytic lesions, as well as 12 (4.27%) studies with hyper-uptake bone metastases without anatomical representation. In interesting cases, we have the follow-up of patients in evaluation of response to treatment who show partial response to 18F-PSMA uptake, but with a considerable increase in the number of osteoblastic lesions. This analysis reveals that there may be a disagreement between the functional (PERSIST) and the anatomical (RESIST) assessment; considering that the molecular precedes the morphological (
● We have 179 studies correlated with PSA. 10.05% (18 studies) were positive with PSA < 1.0, this demonstrates the ability of 18F-PSMA to detect neoplastic activity with low PSA levels.
● We detected 20 studies (7.2%) with supradiaphragmatic lymphadenopathy, which are not so frequent, however, it should be taken into consideration that they may be present in advanced cases of the disease. Supradiaphragmatic extension occurs by hematogenous spread through the vertebral venous system or Batson’s plexus.
● Conventional studies (MRI, ultrasound and CT) have limitations to detect metastatic nodes smaller than 10 mm in the initial staging of patients with high-risk prostate cancer. 18F-PSMA PET/CT has the potential to detect ma-
lignant infiltration in nodes smaller than 5 mm, which can be considered normal on anatomical studies
● Considering the previous points, PET/CT with 18F-PSMA has advantages over bone scintigraphy and computed tomography of the abdomen and pelvis for the staging of prostate cancer.
The authors declare no conflicts of interest regarding the publication of this paper.
Gómez Domínguez, J., Schalch Ponce de León, J.M. and Criales Cortés, J.L. (2021) PET/CT with 18F-PSMA in Patients with Prostate Cancer, Review of the Initial Experience. Open Journal of Urology, 11, 158-175. https://doi.org/10.4236/oju.2021.114015