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1The Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, 325000 Wenzhou, Zhejiang, China
2The Department of Nuclear Medicine, The First Affiliated Hospital of Wenzhou Medical University, 325000 Wenzhou, Zhejiang, China
3The Department of Radiology, The People’s Hospital of Yuhuan, 317600 Yuhuan, Zhejiang, China
*Corresponding Author(s):jixiaowei@wmu.edu.cn (Xiaowei Ji)
| History | Submitted: 02 December 2023 | Accepted: 11 November 2024 | Published: 30 August 2024 |
| Copyright: | ©2024 The Author(s). Published by MRE Press. |
18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography/computed tomograpy (PET/CT) had been increasingly significant in detecting prostate cancer. This study was aimed to assess the usefulness of 18F-PSMA-1007 PET/CT in preoperative evaluation of prostate cancer for the cases with serum total prostate-specific antigen (tPSA) levels between 4 and 10 ng/mL, referred as the PSA gray area. A total of 117 prostate cancer patients in PSA gray area were retrospectively analyzed in the period between March 2019 and December 2022. The independent predictors of extraprostatic extension (EPE) were identified via the Univariate and multivariate analyses. The maximum standardized uptake value (SUVmax) was the only independent predictor of EPE odds ratio (OR), 1.114; 95% confidence interval (CI), 1.040–1.194; p = 0.002). The predicted model’s area under receiver-operating characteristic curves was 75.4%. The sensitivity, specificity and accuracy of 18F-PSMA-1007 PET/CT were calculated for diagnosing the regional lymph node and bone metastases, and obtained as 85.71%, 99.20%, 99.05% and 100%, 97.35%, 99.15%, respectively. In conclusion, SUVmax as compared to the clinical parameters had higher predictive value for EPE in prostate cancer patients within PSA gray area. 18F-PSMA-1007 PET/CT had thus the satisfactory evaluation efficacy for diagnosing the regional lymph node and bone metastases.
Cite this article
Shuying Bian, Meihao Wang, Fei Yao, Dongqin Zhu, Kehua Pan, Yunjun Yang, et al.The value of 18F-PSMA-1007 PET/CT in preoperative evaluation of prostate cancer within PSA gray area.Journal of Men's Health,2024,20(8):109-117 DOI:10.22514/jomh.2024.136
1. Introduction
Prostate cancer (PCa) has the highest occurrence rates among the male cancers in 104 out of 185 countries [1]. It is a malignancy affecting the male urinary system. PCa holds sixth position in China regarding the male cancer-related mortality. It has relatively lower incidence than that in Western nations. However, PCa has started affecting the younger patients because of lifestyle changes [2].
PCa lacks symptoms at the earlier stage which causes difficulties in early PCa management. The European Association of Urology acknowledges serum prostate-specific antigen (PSA) as PCa detection biomarker. The tPSA levels are correlated with PCa diagnosis. The tPSA levels exceeding 10 ng/mL strongly hint cancer. However, it is important whether to diagnose and stage PCa in the “gray area” of tPSA levels between 4.0 ng/mL and 10.0 ng/mL [3, 4, 5]. PSA screening must thus be accompanied by imaging examinations to accurately diagnose PCa [6].
Bone scintigraphy (BS), magnetic resonance imaging (MRI), and computed tomography (CT) can assist in evaluating the high-risk PCa cases [7]. However, assessing the invasiveness of PCa in PSA gray area is challenging because most cases are of low-grade malignancies [7]. The prostate-specific membrane antigen (PSMA) PET/CT is a sensitive imaging tool to accurately reflect the histopathology and metastatic disease compared to the traditional methods. It is applicable even to the patients with low PSA levels [8, 9, 10, 11]. The membrane-bound enzyme PSMA is lowly expressed in benign prostate tissues and highly in prostate cancer epithelial cells [12]. 18F-PSMA-1007 PET/CT has been excellent in recognizing lymph node and bone metastases [13, 14]. Moreover, the European Association of Urology recommend this examination for PCa patients at clinical stage of T3 or higher, indicating extraprostatic extension (EPE). PET/CT images are visually analyzed. Moreover, the maximum standardized uptake value (SUVmax) as a semi-quantitative evaluation of PSMA expression is obtained from PET/CT, being in line with the European Association of Nuclear Medicine standardized reporting guidelines [15]. However, few studies have investigated the application of 18F-PSMA-1007 PET/CT in the PSA gray area. Purpose of this study was thus to evaluate the significance of 18F-PSMA-1007 PET/CT in preoperative assessment of PCa patients in the PSA gray area.
2. Material and methods
2.1 Patients
A total of 418 patients undergone 18F-PSMA-1007 PET/CT at our hospital between March 2019 and December 2022 were initially enrolled. The patients had undertaken radical prostatectomy (RP) and pelvic lymph node dissection (PLND) with histopathologically confirmed PCa. After screening, 117 patients were included in this study (Supplementary Fig. 1a). The exclusion criteria were as follows: (1) tPSA levels outside the gray area, (2) history of other malignancies, (3) history of local or systemic treatments before 18F-PSMA-1007 PET/CT evaluation, and (4) incomplete clinical information or unclear images. The “gray area” in this study referred to the tPSA levels between 4 ng/mL and 10 ng/mL.
2.2 18F-PSMA-1007 PET/CT image scanning
PET/CT (Gemini 64 TF, Philips Medical Systems, Best, The Netherlands) was employed to scan every patient from skull to the middle of thigh. Scans were carried out ~90 min after the intravenous injection of 4.0 MBq/kg 18F-PSMA-1007 (mean ± standard deviation dose: 282.94 ± 34.48 MBq). The following parameters were set for a low-dose CT scan: 140 Kvp tube voltage, 110 mA tube current, 64 × 0.625 mm detector collimation, 0.829 pitch, 0.5 s tube rotation speed, 5 mm section thickness, and 2.5 mm reconstruction thickness. A PET scan was conducted by matching the CT section thickness. Images were acquired in three-dimensional mode with parameters of 576 mm field view, 144 × 144 matrix, and 5 mm slice thickness and interval.
2.3 18F-PSMA-1007 PET/CT image analysis
Images were analysed by a workstation (EBW3.0, Philips). The images were interpreted regarding the primary prostate tumor, pelvic lymph node metastasis and bone metastasis. Tumors were considered positive with the tracer uptake being higher than normal prostate tissue, and the tumor SUVmax was recorded. Metastases was suspected if any lymph node or bone lesion had higher tracer accumulation than the surrounding background [16]. According to the anatomical location, all positive lymph nodes on PET/CT were divided into the areas including left/right external and internal iliac, and left/right obturator areas. This interpretation criterion was consistent with the literature [15, 17]. The images were jointly analyzed by physician and deputy chief physician. They were the nuclear medicine specialists with ten years of experience. Any disagreement was resolved by consensus.
2.4 Collection of clinical and imaging parameters
Clinical parameters including age, serum PSA level, prostate volume (PV), and prostate-specific antigen density (PSAD) were collected from the hospital database. Serum PSA levels were recorded at the initial diagnosis. PV was calculated as: volume = anteroposterior diameter × left-right diameter × vertical diameter × π/6. Diameters were measured at the significant and clearest sections of prostate on CT images [18]. PSAD was calculated as: PSAD = PSA/PV. SUVmax was measured in the region of the highest tracer uptake among primary prostate lesions present in images.
2.5 Comparison between histopathology and PET/CT
Histopathological examinations were conducted for all the patients as per routine, and data were extracted from the pathology reports of RP specimens. The data pertaining to tumor stage, International Society of Urological Pathology (ISUP) grade, and presence of lymph nodes were recorded. PET/CT diagnostic potential was assessed by comparing the imaging and histopathological results. Tumor node metastasis (TNM) staging was analyzed and compared to obtain accurate results (Supplementary Fig. 1b). Histopathological analysis was taken as the reference for EPE and regional lymph node metastasis. Bone metastasis was determined via the clinical follow-up.
2.6 Statistical analysis
SPSS software (version 25.0, IBM, Armonk, NY, USA) was employed for the statistical analyses. Normal distribution variables are presented as mean ± standard deviation, while skewed variables as median (range). Categorical variables are expressed as the number of occurrences (n) and frequency (%). These variables were analyzed by employing Student’s t-test or Mann-Whitney U-test, and chi-square or Fisher’s exact test. The independent predictive factors for EPE were identified by Logistic regression analysis. The predictive models were established by receiver operating characteristic (ROC) curve and the area under ROC curve (AUC) with different parameters. The differences between ROC curves were evaluated by Delong’s test. Sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) were calculated to evaluate the 18F-PSMA-1007 PET/CT performance in diagnosing lymph node and bone metastases. Statistical significance was set at p < 0.05.
3. Results
3.1 Patients
Patient characteristics were given in Table 1. The study included 117 PCa patients with median age of 69 and median tPSA value of 6.72 ng/mL. ISUP grade of the patients ranged from I to V. The median SUVmax of EPE patients was 11.55 (4.50–66.20) compared to that of 8.70 (4.30–31.80) in non-EPE patients (p < 0.001).
| Total patients (n = 117) | EPE patients (n = 52) | Non-EPE patients (n = 65) | p value | ||
| Age (yr) | |||||
| Median (range) | 69.00 (43.00–83.00) | 68.50 (54.00–83.00) | 69.00 (43.00–81.00) | 0.976 | |
| tPSA (ng/mL) | |||||
| Median (range) | 6.72 (4.03–9.97) | 6.83 (4.03–9.72) | 6.70 (4.05–9.97) | 0.750 | |
| fPSA (ng/mL) | |||||
| Median (range) | 0.83 (0.22–2.61) | 0.89 (0.26–2.61) | 0.74 (0.22–1.98) | 0.171 | |
| t/fPSA (ng/mL) | |||||
| Median (range) | 0.11 (0.04–0.36) | 0.11 (0.04–0.34) | 0.11 (0.04–0.34) | 0.249 | |
| PV (mL) | |||||
| Median (range) | 35.88 (12.75–79.67) | 33.71 (12.75–79.67) | 37.70 (20.02–79.61) | 0.183 | |
| PSAD (ng/mL2) | |||||
| Median (range) | 0.18 (0.08–0.46) | 0.19 (0.09–0.46) | 0.17 (0.08–0.39) | 0.200 | |
| SUVmax | |||||
| Median (range) | 9.50 (4.30–66.20) | 11.55 (4.50–66.20) | 8.70 (4.30–31.80) | <0.001 | |
| ISUP, n (%) | |||||
| I | 5 (4.27%) | 1 (1.92%) | 4 (6.15%) | 0.003 | |
| II | 45 (38.46%) | 13 (25.00%) | 32 (49.23%) | ||
| III | 45 (38.46%) | 25 (48.08%) | 20 (30.77%) | ||
| IV | 8 (6.84%) | 4 (7.69%) | 4 (6.15%) | ||
| V | 14 (11.97%) | 9 (17.31%) | 5 (7.70%) | ||
| Clinical TNM stage on 18F-PSMA-1007 PET/CT | |||||
| T stage | |||||
| T2 | 67 (57.26%) | 8 (15.38%) | 59 (90.77%) | <0.001 | |
| T3a | 32 (27.35%) | 30 (57.69%) | 2 (3.08%) | ||
| T3b | 13 (11.11%) | 10 (19.23%) | 3 (4.62%) | ||
| T4 | 5 (4.28%) | 4 (7.70%) | 1 (1.53%) | ||
| N stage | |||||
| N0 | 110 (94.02%) | 45 (86.54%) | 65 (100.00%) | 0.002 | |
| N1 | 7 (5.98%) | 7 (13.46%) | 0 (0.00%) | ||
| M stage | |||||
| M0 | 109 (93.16%) | 47 (90.38%) | 62 (95.38%) | 0.487 | |
| M1 | 8 (6.84%) | 5 (9.62%) | 3 (4.62%) | ||
| Pathological TNM stage | |||||
| T stage | |||||
| T2 | 64 (54.70%) | 0 (0.00%) | 64 (98.46%) | <0.001 | |
| T3a | 35 (29.91%) | 34 (65.38%) | 1 (1.54%) | ||
| T3b | 15 (12.82%) | 15 (28.85%) | 0 (0.00%) | ||
| T4 | 3 (2.56%) | 3 (5.77%) | 0 (0.00%) | ||
| N stage | |||||
| N0 | 113 (96.58%) | 48 (92.31%) | 65 (100.00%) | 0.023 | |
| N1 | 4 (3.42%) | 4 (7.69%) | 0 (0.00%) | ||
| M stage* | |||||
| M0 | 110 (94.02%) | 47 (90.38%) | 63 (96.92%) | 0.931 | |
| M1 | 7 (5.98%) | 5 (9.62%) | 2 (3.08%) | ||
| M stage*: M stage is not determined by bone biopsy, but by clinical follow-up. EPE: extraprostatic extension; PSA: prostate-specific antigen; PV: prostate volume; SUVmax: maximum standardized uptake value; ISUP: international society of urological pathology; PSMA: prostate-specific membrane antigen; CT: computed tomography; PSAD: prostate-specific antigen density; TNM: tumor node metastasis; PET: positron emission tomography. |
3.2 Pathological T stage
3.2.1 Clinical and imaging characteristics
18F-PSMA-1007 PET/CT images of 117 patients depicted different radioactive concentrations in the prostate (Fig. 1). The distribution of T stages for patients undergone RP and pathological specimens available for evaluation was as follows: T2 (54.70%), T3a (29.91%), T3b (12.82%) and T4 (2.56%) (Table 1).
Fig. 1.A patient of bone metastasis with PSA 5.78 ng/mL, GS 4 + 4. (a, b) Abnormally increased PSMA uptake in right glands (red arrow), SUVmax is 28.0. (c, d) The T10 vertebral body with increased PSMA uptake (green arrow), SUVmax is 11.5. (e) No concentration of bone on 99mTc-MDP SPECT. (a, c) fused PET/CT; (b, d) axial PET; (e) 99mTc-MDP SPECT.
3.2.2 EPE prediction by logistic regression analysis
Table 1 showed the details of EPE of patients. PV, PSAD and tPSA did not change much (p > 0.05; Fig. 2a–d), however, significant difference was found in SUVmax between EPE and Non-EPE (p < 0.001). EPE risk was positively correlated with SUVmax as depicted in univariate logistic analysis (odds ratio (OR), 1.097; 95% confidence interval (CI), 1.032–1.167; p = 0.003; Table 2). SUVmax was the only independent predictor of EPE as found in multivariate logistic regression (OR, 1.114; 95% CI, 1.040–1.194; p = 0.002; Table 2).
| Variable | Univariate logistic regression | Multivariate logistic regression | ||||||
| OR | 95% CI | p value | Predictive accuracy, % | OR | 95% CI | p value | Predictive accuracy, % | |
| SUVmax | 1.097 | 1.032–1.167 | 0.003 | 71.0% | 1.114 | 1.040–1.194 | 0.002 | 75.4% |
| Age | 1.009 | 0.954–1.067 | 0.758 | 49.8% | 0.982 | 0.920–1.049 | 0.591 | |
| fPSA | 1.695 | 0.743–3.864 | 0.210 | 57.4% | 3.670 | 0.420–4.699 | 0.116 | |
| tPSA | 1.037 | 0.829–1.298 | 0.749 | 51.7% | 0.624 | 0.307–1.268 | 0.193 | |
| f/tPSA | 1.313 | 0.056–3.101 | 0.252 | 56.2% | 0.000 | 0.000–9.667 | 0.253 | |
| PV | 0.983 | 0.957–1.010 | 0.221 | 57.2% | 0.985 | 0.919–1.055 | 0.666 | |
| PSAD | 2.636 | 0.333–2.880 | 0.142 | 56.9% | 1.812 | 0.000–2.160 | 0.668 | |
| EPE: extraprostatic extension; SUVmax: maximum standardized uptake value; PSA: prostate-specific antigen; PV: prostate volume; OR: odds ratio; CI: confidence interval; PSAD: prostate-specific antigen density. |
3.2.3 Comparing tPSA, SUVmax and combined model by ROC curves for predicting EPE
ROC curves showed the AUC for tPSA as 0.52 (95% CI: 0.42–0.61). The AUC for SUVmax and combined model were 0.71 (95% CI: 0.62–0.79) and 0.75 (95% CI: 0.67–0.83), respectively, both being higher than that for tPSA (p < 0.05; Fig. 3a). SUVmax exhibited the best predictive value compared to clinical parameters.
3.3 Lymph node metastasis
18F-PSMA-1007 PET/CT revealed abnormal pelvic lymph node uptake in 7 of 117 patients. Supplementary Table 1 provided the characteristics of patients with pelvic lymph node metastasis. RP and PLND were conducted based on the patients’ images where 634 lymph nodes were examined. Seven patients had pelvic metastasis with diameter of 0.2 cm–2.1 cm. SE, SP, PPV, NPV and accuracy (ACC) were 100%, 97.35%, 57.14%, 100% and 97.44%, respectively. Seven of 634 examined lymph nodes were positive. The median SUVmax of true-positive lymph node metastasis (LNMs) was larger (9.03 ± 6.17) than that of false-positive LNMs (5.20 ± 1.18). SE, SP, PPV, NPV and ACC at PET/CT were 85.71%, 99.20%, 54.55%, 99.84% and 99.05%, respectively (Table 3).
| For RP patients’ analysis | |||
| n = 117 | HP+ (n = 4) | HP− (n = 113) | |
| PET+ (n = 7) | 4 | 3 | PPV 57.14% |
| PET− (n = 110) | 0 | 110 | NPV 100% |
| SE 100% | SP 97.35% | ACC 97.44% | |
| For PLND nodes analysis of RP patients | |||
| n = 634 | HP+ (n = 7) | HP− (n = 627) | |
| PET+ (n = 11) | 6 | 5 | PPV 54.55% |
| PET− (n = 623) | 1 | 622 | NPV 99.84% |
| SE 85.71% | SP 99.20% | ACC 99.05% | |
| A total of 117 RP patients with PLND were analyzed by histopathology (HP). Sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) in detecting PCa were given in percent. RP: radical prostatectomy; PLND: pelvic lymph node dissection; PET: positron emission tomography. |
3.4 Bone metastasis
The median follow-up time for evaluating bone metastases was 18 months (8–34 months). The common sites of bone lesions in this study were pelvis and spine. Seven patients were identified with PCa having bone metastases on PET/CT images. Six had different degrees of metastatic progression in the clinical follow-up while one had no disease progression. Supplementary Table 2 showed the patients’ details. Three patients underwent PET/CT because of the bone pain where bone metastasis and primary PCa lesion were found. 99mTc-methylene diphosphonic acid (MDP) single-photon emission computed tomography (SPECT) demonstrated metastasis in two patients as depicted by PET/CT, while the other one had bone pain in the clinical follow-up. The treatment regimen was affected as the staging changed from M0 to M1 in above patients (Fig. 1). SE, SP, PPV, NPV and ACC at PET/CT were 100%, 97.35%, 85.71%, 100% and 99.15%, respectively (Table 4).
| n = 117 | Clinical follow up+ (n = 6) | Clinical follow up− (n = 111) | |
| PET+ (n = 7) | 6 | 1 | PPV 85.71% |
| PET− (n = 110) | 0 | 110 | NPV 100.00% |
| SE 100% | SP 97.35% | ACC 99.15% | |
| A total of 117 patients for M stage were analyzed by clinical follow-up. Sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) in detecting PCa were given in percent. PET: positron emission tomography. |
3.5 Associating SUVmax with ISUP
No significant difference was found in PV, PSAD, or tPSA (p > 0.05; Fig. 2e–h), while it was there in SUVmax between ISUP <4 and ISUP ≥4 (p < 0.001). The risk of ISUP ≥4 was positively correlated with SUVmax as found in univariate logistic analysis (OR, 1.126; 95% CI, 1.055–1.202; p < 0.001). SUVmax was the only independent predictor of ISUP ≥4 as revealed in multivariate logistic regression (OR, 1.136; 95% CI, 1.057–1.221; p = 0.001; Supplementary Table 3. ROC curves exhibited the AUC for tPSA as 0.55 (95% CI: 0.45–0.64). AUC for SUVmax and combined model were 0.78 (95% CI: 0.69–0.85) and 0.81 (95% CI: 0.72–0.87), both being higher than tPSA (p < 0.05; Fig. 3b). SUVmax depicted the best predictive value compared to the clinical parameters.
Fig. 2.The differences between EPE and Non-EPE. (a–d) suggest differences in variables between EPE and Non-EPE. (e–h) suggest differences in variables between ISUP <4 and ISUP ≥4. SUVmax: maximum standardized uptake value; PSA: prostate-specific antigen; EPE: extraprostatic extension; PV: prostate volume; ISUP: international society of urological pathology; PSAD: prostate-specific antigen density.
Fig. 3.Comparison of ROC curves. (a) ROC curves comparing tPSA, SUVmax and combined model to predict EPE. AUC to predict EPE was 0.52 for tPSA, 0.71 for SUVmax and 0.75 for combined model. (b) ROC curves comparing tPSA, SUVmax and combined model to predict ISUP ≥4. AUC to predict ISUP ≥4 was 0.55 for tPSA, 0.78 for SUVmax and 0.81 for combined model. tPSA: total prostate-specific antigen; SUVmax: maximum standardized uptake value; AUC: area under ROC curve.
4. Discussion
Evaluation of PCa based on the PSA gray area was challenging. This study was aimed to evaluate the value of 18F-PSMA-1007 PET/CT in PSA gray area. The results demonstrated that PET/CT could predict EPE in patients within PSA gray area, and surpassed the performance of clinical parameters alone. Furthermore, PET/CT was efficient in detecting regional lymph nodes and bone metastases.
Histopathology was the standard criterion for PCa staging, however the detection rates of current detection methods were low in patients with lower PSA levels. 18F-PSMA-1007 PET/CT as a new imaging method had relatively little research conducted.
The concentration of lesions was detected in all patients of this study. Wang et al. [19] concluded that the PSA levels in biochemical recurrence were lower than those in initial diagnosis, however 18F-PSMA-1007 PET/CT could still detect the lesion. In contrast, the PSA gray areas of included patients were the first ones not diagnosed with biochemical recurrence, nonetheless, the results herein showed high accuracy. The histopathological results were staged wherein more than half patients were of T2 stage. This could be attributed to the relatively low PSA levels in most patients. The relationship between the T stage and various parameters was further studied. SUVmax was the only independent predictor of EPE at the tPSA of 4 ng/mL–10 ng/mL. SUVmax (AUC = 0.71) and the combined model (AUC = 0.75) had better predictive value than tPSA (AUC = 0.52; p < 0.05). This confirmed the previous findings [20, 21] that the semi quantitative analysis indicators of PSMA PET/CT imaging including SUVmax, could predict the risk stratification of prostate cancer. If SUVmax of the prostate lesions in PSMA PET/CT was higher than expected, the treatment plan could be adjusted by performing extended PLND or androgen deprivation therapy in suspected EPE patients. SUVmax was thus proved as the only independent predictor of ISUP ≥4 (OR, 1.136; 95% CI, 1.057–1.221; p = 0.001). ISUP ≥4 indicated a high PCa risk. The biopsy ISUP was not always consistent with the pathological ISUP. Therefore, SUVmax might predict the pathological ISUP more reliably compared to the biopsy ISUP and the other less sensitive clinical variables. The patients with high SUVmax might skip the biopsy and directly undergo the next treatment steps. In this study, the multivariate analyses revealed that none of the clinical parameters were independent predictors of PSA range. Studies [22, 23, 24] had reported that the clinical parameters including age, PV and PSAD were not the predictors in these patients. PCa patients usually had prostate hyperplasia. The changes in prostate size caused by hyperplasia might affect PSAD in the males with tPSA levels of 4 ng/mL–10 ng/mL. The predictive value of these clinical indicators remained controversial within PSA gray areas. The racial differences and sample selection biases might be responsible for this result.
Some patients did not undergo PLND because of the low preoperative risk of lymph node involvement. The specificity and accuracy of 18F-PSMA-1007 PET/CT in detecting lymph node metastases were satisfactory in this study. Previous investigations proved that PET/CT had greater specificity for LNM staging of intermediate-risk or high-risk PCa [25]. This study further depicted that 18F-PSMA-1007 PET/CT was accurate for the LNM staging in PCa patients and with low PSA values. Researchers using histopathology for the validation had demonstrated that PET/CT possessed sufficient diagnostic value in LNM staging by employing 68Ga-PSMA as a tracer. 18F-PSMA had rarely been studied [21, 26, 27]. A precedent was thus set to prove 18F-PSMA-1007 PET/CT being applicable for lymph node staging.
Distant metastases were important for the prognosis which emphasized clinical importance of their detection. 18F-PSMA-1007 PET/CT showed the diagnostic accuracy of 99.15%, being consistent with the previous studies [28, 29]. Sometimes, the concentration focus on PET/CT could not be observed on 99mTc-MDP SPECT because of the difference in imaging principles of two methods. Bone uptake of 99mTc-MDP was related to the osteoblast activity, vascularization and environmental factors. PCa bone metastasis triggered an osteoblast response and accumulated large amounts of 99mTc-MDP. PSMA PET/CT was more sensitive to detect bone metastases than BS in the patients of PSA <10 ng/mL [30]. There was no concentration of 99mTc-MDP SPECT in the patient whose PSMA PET/CT was positive (Fig. 1). This did not completely rule out the metastasis possibility. A possible reason could be that the follow-up time was not long enough, and focus was not osteogenic. This patient should thus be continued with active treatment because of bone pain symptoms. Early detection of PSMA PET/CT for bone metastasis could determine the appropriate treatment plan.
This study had several limitations. The selection bias might impact the findings as it was a retrospective study with small sample size and carried out at a single center. Furthermore, bone metastases were not confirmed by histopathology as the confirmatory biopsies were not routinely performed for suggestive bone lesions. Therefore, it was planned to validate these results in a prospective study with multicenter data, and conduct subgroup analysis of different T stages. Furthermore, the follow-up time for the metastatic patients should be prolonged to attain more accurate prognosis. Future studies would focus these areas.
5. Conclusions
This study evaluated the potential of 18F-PSMA-1007 PET/CT in preoperative evaluation of prostate cancer within PSA gray area. It exhibited an excellent diagnostic performance for EPE, lymph node metastasis, and bone metastasis.
Abbreviations
PSMA, prostate-specific membrane antigen; PET, positron emission tomography; PSA, prostate-specific antigen; RP, radical prostatectomy; PCa, prostate cancer; SUVmax, maximum standardized uptake value; PSAD, prostate-specific antigen density; ISUP, international society of urologic pathology; mpMRI, multiparametric magnetic resonance imaging; CT, computed tomography; BS, bone scintigraphy; ROC, receiver operating characteristic; PLND, pelvic lymph node dissection; TNM, tumor node metastasis; LNM, lymph node metastasis; ACC, accuracy; MDP, methylene diphosphonic acid; SPECT, single-photon emission computed tomography.
Availability of data and materials
The data presented in this study are available on reasonable request from the corresponding author.
Author contributions
SYB—wrote the original manuscript; MHW and FY—interpreted the data and prepared the tables and figures; KHP and DQZ—acquired the data; YJY—contributed to the conception and design of the study; KT and WFH—contributed to the conception and design of the study; XWJ—revised the manuscript for intellectual content. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.
Ethics approval and consent to participate
This retrospective study was approved by the Johns Hopkins Institutional Review Board (KY2022-R012) and carried out in accordance with the Declaration of Helsinki. The patients provided written informed consent to participate in this study.
Acknowledgment
Not applicable.
Funding
This research was funded by the Key Laboratory of Intelligent Medical Imaging of Wenzhou (No. 2021HZSY0057), the Taizhou Science and Technology Project (Grant No. 20ywb 156), the Wenzhou Major Program of Science and Technology Innovation (Grant No. ZY2020012) and the Key Laboratory of Novel Nuclide Technologies on Precision Diagnosis and Treatment & Clinical Transformation of Wenzhou City (No. 2023HZSY0012).
Conflict of interest
The authors declare no conflict of interest.
Supplementary material
Supplementary material associated with this article can be found, in the online version, at https://oss.jomh.org/ files/article/1829450036915650560/attachment/ Supplementary%20material.docx.
