Skip to main content
EJNMMI Research
Download PDF
  • Original research
  • Open access
  • Published:

Impact of non-regional lymph node metastases accurately revealed on 18F-PSMA-1007 PET/CT in the clinical management of metastatic hormone-sensitive prostate cancer

EJNMMI Research volume 13, Article number: 64 (2023) Cite this article

Abstract

Background

Non-regional lymph node (NRLN) metastases has shown increasing importance in the prognosis evaluation and clinical management of primary metastatic hormone-sensitive prostate cancer (mHSPC). Hence, this study aimed to investigate the concordance rates between 18F-PSMA-1007 PET/CT and conventional imaging (CI) in revealing NRLN metastases, and explore the impact of NRLN metastases on the management of primary mHSPC.

Methods

The medical records of 224 patients with primary mHSPC were retrospectively reviewed, including 101 patients (45.1%) only received CI for TNM classification, 24 patients (10.7%) only received 18F-PSMA-1007 PET/CT, and 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI. Among patients who received 18F-PSMA-1007 PET/CT and CI before initial treatment, the concordance rates between 18F-PSMA-1007 PET/CT and CI were analyzed. The high-volume disease was defined as the presence of visceral metastases and/or ≥ 4 bone metastases (≥ 1 beyond the vertebral bodies or the pelvis) based on the findings of 18F-PSMA-1007 PET/CT and/or CI. The primary endpoint was progression-free survival (PFS), and Cox regression analyses were performed to explore independent predictors of PFS.

Results

A total of 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI, the concordance rate in revealing NRLN metastases between 18F-PSMA-1007 PET/CT and CI was only 61.62%, and Cohen’s kappa coefficient was as low as 0.092. Moreover, 18F-PSMA-1007 PET/CT detected an additional 37 of 94 (39.4%) patients with positive NRLNs who were negative on CI. Cox regression revealed that androgen deprivation therapy (ADT), N1, high-volume, NRLN and visceral metastases were associated with worse PFS (all P < 0.05) in 224 patients. Furthermore, in patients with low-volume disease, the median PFS of patients with NRLN metastases was significantly shorter than that of patients without NRLN metastases (19.5 vs. 27.5 months, P = 0.01), while the difference between patients with low-volume plus NRLN metastases and high-volume disease was not significant (19.5 vs. 16.9 months, P = 0.55). Moreover, early docetaxel chemotherapy significantly prolonged the PFS of these patients compared with ADT alone (20.7 vs. 12.3 months, P = 0.008).

Conclusion

NRLN metastases could be accurately revealed by 18F-PSMA-1007 PET/CT, which should be considered a high-volume feature, especially concomitant with bone metastases. Furthermore, patients with low-volume plus NRLN metastases may be suitable for more intensive treatment, such as early docetaxel chemotherapy.

Background

Prostate cancer (PCa) is the second most common cancer in men worldwide, and approximately 68% of primary patients present with metastatic hormone-sensitive PCa (mHSPC) in China [1, 2]. Androgen deprivation therapy (ADT) is the mainstay therapy for primary mHSPC, while the durability of response to ADT and time to castration resistance is variable owing to the significant heterogeneity of mHSPC [3,4,5]. In the past few years, the treatment paradigm of mHSPC has tremendously changed, and docetaxel, abiraterone and enzalutamide have been sequentially approved as first-line treatment options for primary mHSPC [6].

As proposed in the CHAARTED trials, the localization and number of metastases are widely used to categorize mHSPC into low- or high-volume disease for risk stratification and treatment selection purposes [7]. As we all know, the common sites of metastasis from PCa, in order of decreasing frequency, are the bone (84%), distant lymph nodes (10.6%), liver (10.2%) and thorax (9.1%) [8]. However, this classification only focused on the status of bone and visceral metastases and did not include non-regional lymph node (NRLN) metastases. Emerging evidence suggests that NRLN metastases is an important prognostic factor for mHSPC, especially concomitant with bone metastases [9, 10]. Furthermore, a study conducted by Shiota et al. showed that NRLN metastases were associated with worse progression-free survival (PFS) than bone metastases, especially in patients with low-volume diseases [11]. Thus, in addition to bone or visceral metastases, NRLN metastases should be included as another risk factor to classify low- or high-volume disease, but the clinical application value of NRLN metastases is limited by its detection rate, which is as low as 9–12% [12, 13].

Currently, conventional imaging (CI) modalities, including computerized tomography (CT) or magnetic resonance imaging (MRI), are recommended to evaluate metastatic spread to lymph nodes, and morphological changes in lymph nodes are the main diagnostic criterion [14, 15]. However, morphologic changes frequently lag behind functional changes, making it difficult for CI to identify small metastatic lesions and distinguish metastases from inflammation, which leads to the low sensitivity and specificity of CI in detecting NRLN metastases [16]. Prostate-specific membrane antigen (PSMA) is expressed on PCa cells and often shows marked overexpression in metastatic PCa tissue [17, 18]. Therefore, PSMA PET/CT may be a more promising technique for accurately detecting NRLN metastases than CI. Furthermore, the definition of low- and high-volume disease in the CHAARETED trial was based upon CI, and studies exploring the concordance rates between PSMA PET/CT and CI in terms of tumor volume evaluation are limited. To address this void, we analyzed a consecutive cohort of patients with primary mHSPC who received PSMA PET/CT or CI before initial treatment. We hypothesized that PSMA PET/CT could detect more NRLN metastases, which might affect tumor volume evaluation and treatment selection.

Methods

Patients and study design

From January 2019 to December 2021, all patients with primary mHSPC who underwent 18F-PSMA-1007 PET/CT or CI before initial treatment were identified in our database. Patients who had received local or systemic treatment before imaging examination, had prior invasive malignancy or any serious comorbidity and had incomplete data were excluded. A total of 224 patients were included in the final analyses. This study was approved by the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China. All subjects signed an informed consent form.

Basic information, laboratory values, and imaging examination findings, such as age, biopsy Gleason score (GS), prostate-specific antigen (PSA) at diagnosis, primary treatment and imaging examination modality, metastatic sites, etc., of these patients were retrospectively reviewed.

According to CHAARTED, the high-volume disease was defined as the presence of visceral metastases and/or ≥ 4 bone metastases (≥ 1 beyond the vertebral bodies or the pelvis) based on the findings of 18F-PSMA-1007 PET/CT and/or CI [7]. Patients who did not meet the criteria of high-volume disease were defined as low-volume disease. For patients who received both 18F-PSMA-1007 PET/CT and CI before initial treatment, the discrepancies between 18F-PSMA-1007 PET/CT and CI were resolved by discussion.

Conventional imaging

CI included chest, abdominal, and pelvic cross-sectional imaging (i.e., CT or MRI) and Tc-99 m bone scintigraphy. When dimensions on lymph nodes were available, a lymph node with a short axis of ≥ 1 cm was considered suspicious for metastasis. Otherwise, a lymph node was deemed “positive” if classified as such by the interpreting radiologist in the clinical report.

18F-PSMA-1007 acquisition and imaging analysis

18F-PSMA-1007 was synthesized as described in the literature [19]. The reagent kits, PSMA-1007 precursor, and PSMA-1007 reference standard were purchased from ABX Advanced Biochemical Compounds GmbH, Germany. A whole-body PET/CT scan was conducted using the GEMINI TF64 PET/CT system (Philips Health care). 18F-PSMA-1007 was injected intravenously at a weight-based dose of 97–316 MBq for 90 min before acquisition began. The variation in injected dose was due to the large-scale patients serving at each production (18–20 patients), resulting in lower activity for the last one or two patients each time. However, the image quality of the PET scans in patients administered low activity was good and judged sufficient for accurate image analysis [20]. All 18F-PSMA-1007 PET/CT images were analyzed using Fusion Viewer software in the Extended Brilliance Workstation (EBW, Philips, Netherlands). Lesions in the whole body with uptake above the background activity were defined as metastases. All PET/CT images were reviewed by 2 blinded nuclear physicians, and discrepancies were resolved by discussion.

Follow-up and outcome measures

Patients were followed up every month for the first 3 months and every 3 months thereafter with PSA tests and CI examinations. NRLN metastases included positive lymph nodes of the abdominal, inguinal, and upper diaphragm. For patients who received 18F-PSMA-1007 PET/CT and CI before initial treatment, the concordance rate of 18F-PSMA-1007 PET/CT with CI for the identification of T and N stage and metastatic sites was analyzed. The endpoint of survival evaluation was PFS, which was defined as the time from treatment beginning to biochemical and/or clinical/radiological progression (based on the results of CI examinations) or cancer-specific death, whichever occurred first [21].

Statistical analysis

Data for continuous variables are presented as the mean ± standard deviation, and categorical data are displayed as numbers (percentage). The concordance rates between 18F-PSMA-1007 PET/CT and CI were assessed by Cohen’s kappa coefficient. Cox regression analyses were performed to explore independent predictors of PFS. Survival curves were generated using the Kaplan‒Meier method, and log-rank tests were used to compare the differences. Statistical analysis was performed using SPSS 23.0 for Windows (SPSS, Chicago, IL). All tests were 2-tailed, and p < 0.05 was considered to be statistically significant.

Results

Baseline characteristics

As shown in Table 1, the mean age and PSA at diagnosis of the 224 patients were 70.27 ± 8.85 and 531.02 ± 1055.28 ng/mL, respectively. A total of 142 patients (63.4%) had biopsy GSs of 9–10, and 132 patients (58.9%) had high-volume disease. Ninety-four patients (42.0%) were treated with ADT, and 130 patients (58.0%) were treated with ADT combined with docetaxel. Before treatment, 101 patients (45.1%) only received CI for TNM classification, 24 patients (10.7%) only received 18F-PSMA-1007 PET/CT, and 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI. Then, 162 patients (72.3%) were diagnosed with clinical tumor T stage ≥ 3, and 139 patients (62.1%) were positive for clinical N stage (N1). Moreover, NRLN metastases were found in 55 patients (24.6%), bone metastases were found in 208 patients (92.9%), and visceral metastases were found in 22 patients (9.8%). The median follow-up and PFS of 224 patients were 27.38 ± 8.69 and 17.56 ± 8.32 months, respectively.

Table 1 Baseline characteristics
Full size table

Concordance rate between CI and 18F-PSMA-1007 PET/CT

Representative images of metastasis distribution on 18F-PSMA-1007 PET/CT in mHSPC with different tumor volumes are shown in Fig. 1. Among 99 patients who received both 18F-PSMA-1007 PET/CT and CI before treatment, there were 19 patients with miT2 (19.19%), 36 patients with miT3 (36.36%) and 44 patients with miT4 (44.45%), and there were 19 patients with miN0 (19.19%), 37 patients with miN1 (37.37%) and 43 patients with miN2 (43.44%). Furthermore, the concordance rates between CI and 18F-PSMA-1007 PET/CT in terms of tumor volume, T stage, N stage, bone metastases, and visceral metastases were 90.91%, 89.90%, 84.85%, 82.83%, and 86.87%, respectively (Table 2). However, the concordance rate in revealing NRLN metastases was only 61.62%, and Cohen’s kappa coefficient was as low as 0.092.

Fig. 1
figure 1

Representative images of metastasis distribution on 18F-PSMA-1007 PET/CT in mHSPC with different tumor volumes

Full size image
Table 2 The concordance rate between 18F-PSMA-1007 PET/CT and CI
Full size table

The difference of NRLN metastases detection rates between CI and 18F-PSMA-1007 PET/CT

The detection rates of NLRN metastases for 18F-PSMA-1007 PET/CT and 18F-PSMA-1007 PET/CT + CI were 33.33% (8/24), 42.42% (42/99), respectively. However, the detection rates of NRLN metastases for CI was only 4.95% (5/101), which was significantly lower than 18F-PSMA-1007 PET/CT and 18F-PSMA-1007 PET/CT + CI (4.95% vs. 33.33%, 4.95% vs. 42.42%, P < 0.05). Among 123 patients who received 18F-PSMA-1007 PET/CT before treatment, the patient-based analysis showed that the detection rate of NRLN metastases was 39.83% (49/123). However, the detection rate of NRLN metastases was only 5.00% (10/200) in 200 patients who received CI before treatment, which was significantly lower than 18F-PSMA-1007 PET/CT (5.00% vs. 39.83%, P < 0.05). Furthermore, the lesion-based analysis also showed that the detection rates of NLRN metastases for CI was significantly lower than 18F-PSMA-1007 PET/CT (3.87% vs. 36.24%, P < 0.05).

Prognostic factors of PFS in primary mHSPC

Of the 224 patients included in the present study, 146 patients (65.2%) had diseases progression during the period of follow-up. Univariate Cox regression revealed that primary treatment modality, tumor volume, N stage, and the metastatic status of NRLNs and visceral organs were associated with PFS (Table 3). After reintegrating all the above five variables in the Cox regression model, the multivariate analysis suggested that ADT, N1, high-volume and visceral metastases were also associated with worse PFS (all P < 0.05). Furthermore, the risk of disease progression was decreased by half in the absence of NRLN metastases.

Table 3 Cox regression analysis for associations of clinicopathological parameters with PFS
Full size table

Exploratory analysis

Of the 224 patients, the median PFS of patients without NRLN metastases was 23.0 months, which was significantly longer than that of patients with NRLN metastases (23.0 vs. 17.0 months, P = 0.001) (Fig. 2A). Among patients with low-volume disease, the median PFS of patients with NRLN metastases was only 19.5 months, which was significantly shorter than that of patients without NRLN metastases (19.5 vs. 27.5 months, P = 0.001) (Fig. 2B). In the subgroup of patients with high-volume disease, the difference was not observed between patients with and without NRLN metastases (14.5 vs. 17.5 months, P = 0.15) (Fig. 2C). However, the difference in PFS between patients with low-volume plus NRLN metastases and high-volume disease was not significant (19.5 vs. 16.9 months, P = 0.55) (Fig. 2D). Furthermore, for patients with low-volume disease but concomitant NRLN metastases, ADT combined with early docetaxel chemotherapy significantly prolonged PFS compared with ADT alone (20.7 vs. 12.3 months, P = 0.008) (Fig. 2E).

Fig. 2
figure 2

Kaplan‒Meier estimates of the impact of non-regional lymph node (NRLN) metastases on progression-free survival (PFS) for all patients with mHSPC in this study (A), patients with low-volume disease (B), and patients with high-volume disease (C). PFS was compared between patients with low-volume disease plus NRLN metastases and patients with high-volume disease (D). PFS was compared among patients with low-volume disease and NRLN metastases by different treatment arms (E)

Full size image

Discussion

Tumor volume is a critical factor for treatment decision-making in primary mHSPC. In addition to bone and visceral metastases, NRLN metastases may be an important additional factor for distinguishing between low- and high-volume diseases. In the current study, we focused on the cohort of primary mHSPC and found that the concordance rates of 18F-PSMA-1007 PET/CT and CI in detecting bone and visceral metastases were 82.83% and 86.87%, respectively, while the concordance rate in detecting NRLN metastases was only 61.62%. Among 94 patients without NRLN metastases on CI, NRLN metastases were detected by 18F-PSMA-1007 PET/CT in 37 patients (39.4%). Thus, we deduced that 18F-PSMA-1007 PET/CT had a higher sensitivity and specificity in detecting NRLN metastases than CI, which provided new insight into the clinical management of mHSPC.

Recently, PSMA PET/CT has shown increasing importance in the comprehensive management of PCa, including presurgical staging [22], biochemical recurrence prediction [23], and lymph node metastasis detection [24]. The diagnosis of lymph node metastases on CI mainly depends on the morphological size. However, the majority of metastatic nodes from PCa are < 8 mm [25], which does not satisfy the CI morphological size of lymph node metastases. Thus, tiny lymph node metastases of < 8 mm were inevitably missed by CI. Several studies have demonstrated that 68Ga-PSMA-11 PET/CT can provide a pattern of metastatic spread of lymph node metastases with higher sensitivity and specificity than CI and detect more NRLN metastases [26, 27]. Furthermore, a study conducted by Lenis et al. noted that the non-concordance rate between CI and 68Ga-PSMA-11 PET/CT was nearly 30%, and 68Ga-PSMA-11 PET/CT identified 20% of pelvic nodal disease and up to 10% of distant metastatic disease that was negative on CI [28]. To the best of our knowledge, this is the first study to evaluate the concordance rates between 18F-PSMA-1007 PET/CT and CI in terms of tumor volume evaluation and TNM classification. In the subset of patients who received 18F-PSMA-1007 PET/CT and CI before initial treatment, we found that 18F-PSMA-1007 PET/CT could detect more bone and visceral metastases that were negative on CI, but the effects of these additional findings on tumor volume evaluation were limited, as the concordance rate of tumor volume evaluation was 90.91%, and only 9 patients upgraded from low-volume to high-volume disease. Furthermore, Barbato et al. also noted that PSMA-PET criteria with volume quantification deliver comparable with CHAARTED criteria, with only 13% misalignment [29]. However, 18F-PSMA-1007 PET/CT detected an additional 37 of 94 (39.4%) patients with positive NRLNs who were negative on CI. Among 94 patients without NRLN metastases on CI, the median PFS of 37 patients with NRLN metastases on 18F-PSMA-1007 PET/CT was 18.0 months, which was significantly shorter than that of patients without NLRN metastases both on CI and 18F-PSMA-1007 PET/CT (18.0 vs. 25.0 months, P = 0.01) (Additional file 1: Fig. S1). In addition, 55 patients (58.5%) had diseases progression during the period of follow-up. Univariate Cox regression revealed that primary treatment modality, NRLN metastases detected by 18F-PSMA-1007 PET/CT were associated with PFS (Additional file 2: Table S1). Subsequently, the multivariate Cox analysis including all the above two variables suggested that ADT, NRLN metastases detected by 18F-PSMA-1007 PET/CT were also associated with worse PFS (all P < 0.05).

Furthermore, among 224 patients with primary mHSPC, we also found that NRLN metastases was an independent prognostic factor, and the progression risk of disease increased by twofold in patients with NLRN metastases. Ali et al. identified 17,167 patients who were diagnosed with mHSPC in the Surveillance, Epidemiology, and End Results database and noted that patients with bone and NRLN metastases had a significantly higher risk of all-cause mortality and prostate cancer-specific mortality [13]. Recently, Heesterman et al. also found that the presence of concomitant NRLNs and bone metastases was a poor prognostic sign, especially in patients with low-volume mHSPC [12]. Subsequently, a study also demonstrated that increased metastatic burden of 5 or more nodal metastases was associated with worse outcomes in patients with mHSPC either treated with ADT combined with docetaxel or ADT alone [30]. Moreover, our study further identified a special population with low-volume disease but with NRLN metastases. The PFS of these patients was 19.5 months, which was similar to that of high-volume disease but significantly shorter than that of patients with low-volume disease without NRLN metastases. This phenomenon warned that NRLN metastases, especially synchronous with bone metastases, should be considered a high-risk feature with metastatic volume stratification definitions to improve the accuracy of disease volume-based treatment decisions.

The management of NRLN metastases remains a challenge for urologists, and metastatic volume evaluation might be helpful. Tumor volume classification, as proposed in the CHAARTED trials, is universally accepted for use in clinical practice or clinical trial conduct. For primary mHSPC synchronous with NRLN metastases, several studies have shown that local treatment combined with systemic therapy could improve the prognosis compared with systemic therapy alone [31]. However, we should pay more attention to interpreting these results, as the potential benefit of local treatment depends largely on the characteristics of the primary tumor and the number of suspicious nodes [32]. Prospective data from arm H of the STAMPEDE trial showed that the survival benefit of prostate radiotherapy decreased continuously as the number of bone metastases increased, with the benefit most pronounced with up to three bone metastases [33]. Furthermore, they also noted that the magnitude of benefit from the addition of prostate radiation therapy was greater in patients with only NRLN metastases, which indicated that only patients with very low metastatic burden (only NRLN metastases) or oligometastatic status (three or fewer bone metastases without visceral metastasis) might benefit more from local treatment. Previously, the CHAARTED trial showed that docetaxel could improve the prognosis for mHSPC patients with high-volume disease, but the benefit of docetaxel was not observed for patients with low-volume disease [7]. As mentioned above, coexisting NRLNs and bone metastases represented a high metastatic burden, even in patients with low-volume disease. Recently, the 2023 EAU guidelines recommended that all men with mHSPC should receive intensified ADT + androgen receptor signaling inhibitors (ARSI) or triple therapy (ADT + ARSI + docetaxel) [15]. However, the most suitable population for triple therapy is still unknown, and multi-drug combination therapy might result in more toxicity events. Thus, ADT combined with docetaxel or ARSI was still first-line treatment option for patients with primary mHSPC in clinical practice. Previously, several studies demonstrated that ADT combined docetaxel could improve the prognosis for mHSPC patients with high-volume disease, but the benefit of docetaxel was not observed for patients with low-volume disease. In the present study, we found that patients with low-volume plus NRLN metastases had a poor prognosis and could benefit more from docetaxel than ADT alone. Herein, we suggested that the metastatic burden of patients with low-volume plus NRLN metastases was remarkably higher than that of patients with low-volume without NRLN metastases but similar to that of patients with high-volume disease, and early intensive treatments, such as docetaxel, should be performed for these patients.

Despite these positive results in this real-world retrospective study, there also had several limitations. First, the retrospective nature of the present study and the small sample size from a single center might cause selection bias. Second, a part of patients only received CI examination, might indicate insufficient metastatic screening and tumor volume evaluation. Moreover, due to the short follow-up time, the impact of NRLN metastases on overall survival was not analyzed, and a longer follow-up duration might produce more positive findings. Lastly, only less of half the patients in our study had both received 18F-PSMA-1007 PET/CT and CI before treatment and there was no standard of reference for the assessment of diagnostic performance in our study. Hence, further prospective multicenter studies are needed to support our findings.

Conclusions

In the present study, we found that the concordance rates between 18F-PSMA-1007 PET/CT and CI in terms of tumor volume evaluation were comparable. However, the concordance rate between 18F-PSMA-1007 PET/CT and CI in detecting NRLN metastases was very low, as 18F-PSMA-1007 PET/CT could reveal more NRLN metastases, which was an important prognostic factor for primary mHSPC. Furthermore, in patients with low-volume disease, the presence of concomitant NRLN metastases is a poor prognostic sign compared to patients without NRLN metastases, and more intensive treatment, such as early docetaxel chemotherapy, may be more suitable for these patients.

Availability of data and materials

The datasets generated during the current study are available from the corresponding author on reasonable request.

Abbreviations

NRLN:

Non-regional lymph node

mHSPC:

Metastatic hormone-sensitive prostate cancer

CI:

Conventional imaging

PFS:

Progression-free survival

ADT:

Androgen deprivation therapy

PCa:

Prostate cancer

CT:

Computerized tomography

MRI:

Magnetic resonance imaging

PSMA:

Prostate-specific membrane antigen

GS:

Gleason score

PSA:

Prostate-specific antigen

References

  1. Hassanipour-Azgomi S, Mohammadian-Hafshejani A, Ghoncheh M, Towhidi F, Jamehshorani S, Salehiniya H. Incidence and mortality of prostate cancer and their relationship with the Human Development Index worldwide. Prostate Int. 2016;4:118–24. https://doi.org/10.1016/j.prnil.2016.07.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32. https://doi.org/10.3322/caac.21338.

    Article  PubMed  Google Scholar 

  3. Tangen CM, Hussain MH, Higano CS, Eisenberger MA, Small EJ, Wilding G, et al. Improved overall survival trends of men with newly diagnosed M1 prostate cancer: a SWOG phase III trial experience (S8494, S8894 and S9346). J Urol. 2012;188:1164–9. https://doi.org/10.1016/j.juro.2012.06.046.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wu JN, Fish KM, Evans CP, Devere White RW, Dall’Era MA. No improvement noted in overall or cause-specific survival for men presenting with metastatic prostate cancer over a 20-year period. Cancer. 2014;120:818–23. https://doi.org/10.1002/cncr.28485.

    Article  CAS  PubMed  Google Scholar 

  5. Gravis G, Boher JM, Fizazi K, Joly F, Priou F, Marino P, et al. Prognostic factors for survival in noncastrate metastatic prostate cancer: validation of the glass model and development of a novel simplified prognostic model. Eur Urol. 2015;68:196–204. https://doi.org/10.1016/j.eururo.2014.09.022.

    Article  PubMed  Google Scholar 

  6. Weiner AB, Nettey OS, Morgans AK. Management of metastatic hormone-sensitive prostate cancer (mHSPC): an evolving treatment paradigm. Curr Treat Options Oncol. 2019;20:69. https://doi.org/10.1007/s11864-019-0668-8.

    Article  PubMed  Google Scholar 

  7. Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018;36:1080–7. https://doi.org/10.1200/JCO.2017.75.3657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Gandaglia G, Abdollah F, Schiffmann J, Trudeau V, Shariat SF, Kim SP, et al. Distribution of metastatic sites in patients with prostate cancer: a population-based analysis. Prostate. 2014;74:210–6. https://doi.org/10.1002/pros.22742.

    Article  PubMed  Google Scholar 

  9. Pond GR, Sonpavde G, de Wit R, Eisenberger MA, Tannock IF, Armstrong AJ. The prognostic importance of metastatic site in men with metastatic castration-resistant prostate cancer. Eur Urol. 2014;65:3–6. https://doi.org/10.1016/j.eururo.2013.09.024.

    Article  PubMed  Google Scholar 

  10. James ND, Spears MR, Clarke NW, Dearnaley DP, De Bono JS, Gale J, et al. Survival with newly diagnosed metastatic prostate cancer in the “docetaxel era”: data from 917 patients in the control arm of the STAMPEDE trial (MRC PR08, CRUK/06/019). Eur Urol. 2015;67:1028–38. https://doi.org/10.1016/j.eururo.2014.09.032.

    Article  PubMed  Google Scholar 

  11. Shiota M, Terada N, Saito T, Yokomizo A, Kohei N, Goto T, et al. Differential prognostic factors in low- and high-burden de novo metastatic hormone-sensitive prostate cancer patients. Cancer Sci. 2021;112:1524–33. https://doi.org/10.1111/cas.14722.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Heesterman BL, van der Poel HG, Schoots IG, Mehra N, Aben KKH. Prognostic importance of concomitant non-regional lymph node and bone metastases in men with newly diagnosed metastatic prostate cancer. BJU Int. 2022;130:217–25. https://doi.org/10.1111/bju.15632.

    Article  PubMed  Google Scholar 

  13. Ali A, Hoyle A, Mistry H, Clarke NW. Importance of non-regional lymph nodes in assigning risk in primary metastatic prostate cancer. BJU Int. 2019;123:65–73. https://doi.org/10.1111/bju.14400.

    Article  PubMed  Google Scholar 

  14. Schaeffer EM, Srinivas S, Adra N, An Y, Barocas D, Bitting R, et al. NCCN guidelines(R) insights: prostate cancer, version 1.2023. J Natl Compr Canc Netw. 2022;20:1288–98. https://doi.org/10.6004/jnccn.2022.0063.

    Article  CAS  PubMed  Google Scholar 

  15. EAU Guidelines. Edn. Presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-19-6.

  16. Kuten J, Fahoum I, Savin Z, Shamni O, Gitstein G, Hershkovitz D, et al. Head-to-head comparison of (68)Ga-PSMA-11 with (18)F-PSMA-1007 PET/CT in staging prostate cancer using histopathology and immunohistochemical analysis as a reference standard. J Nucl Med. 2020;61:527–32. https://doi.org/10.2967/jnumed.119.234187.

    Article  CAS  PubMed  Google Scholar 

  17. Li R, Ravizzini GC, Gorin MA, Maurer T, Eiber M, Cooperberg MR, et al. The use of PET/CT in prostate cancer. Prostate Cancer Prostatic Dis. 2018;21:4–21. https://doi.org/10.1038/s41391-017-0007-8.

    Article  PubMed  Google Scholar 

  18. Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016;13:226–35. https://doi.org/10.1038/nrurol.2016.26.

    Article  CAS  PubMed  Google Scholar 

  19. Cardinale J, Martin R, Remde Y, Schafer M, Hienzsch A, Hubner S, et al. Procedures for the GMP-compliant production and quality control of [(18)F]PSMA-1007: a next generation radiofluorinated tracer for the detection of prostate cancer. Pharmaceuticals (Basel). 2017. https://doi.org/10.3390/ph10040077.

    Article  PubMed  Google Scholar 

  20. Uprimny C, Kroiss AS, Decristoforo C, Fritz J, von Guggenberg E, Kendler D, et al. (68)Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44:941–9. https://doi.org/10.1007/s00259-017-3631-6.

    Article  CAS  PubMed  Google Scholar 

  21. Hussain M, Tangen CM, Higano C, Schelhammer PF, Faulkner J, Crawford ED, et al. Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol. 2006;24:3984–90. https://doi.org/10.1200/JCO.2006.06.4246.

    Article  PubMed  Google Scholar 

  22. Sonni I, Eiber M, Fendler WP, Alano RM, Vangala SS, Kishan AU, et al. Impact of (68)Ga-PSMA-11 PET/CT on staging and management of prostate cancer patients in various clinical settings: a prospective single-center study. J Nucl Med. 2020;61:1153–60. https://doi.org/10.2967/jnumed.119.237602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rousseau E, Wilson D, Lacroix-Poisson F, Krauze A, Chi K, Gleave M, et al. A prospective study on (18)F-DCFPyL PSMA PET/CT imaging in biochemical recurrence of prostate cancer. J Nucl Med. 2019;60:1587–93. https://doi.org/10.2967/jnumed.119.226381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Luiting HB, van Leeuwen PJ, Busstra MB, Brabander T, van der Poel HG, Donswijk ML, et al. Use of gallium-68 prostate-specific membrane antigen positron-emission tomography for detecting lymph node metastases in primary and recurrent prostate cancer and location of recurrence after radical prostatectomy: an overview of the current literature. BJU Int. 2020;125:206–14. https://doi.org/10.1111/bju.14944.

    Article  CAS  PubMed  Google Scholar 

  25. Briganti A, Larcher A, Abdollah F, Capitanio U, Gallina A, Suardi N, et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol. 2012;61:480–7. https://doi.org/10.1016/j.eururo.2011.10.044.

    Article  PubMed  Google Scholar 

  26. Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of (68)Gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol. 2016;195:1436–43. https://doi.org/10.1016/j.juro.2015.12.025.

    Article  PubMed  Google Scholar 

  27. Jiao J, Quan Z, Zhang J, Wen W, Qin J, Yang L, et al. The establishment of new thresholds for PLND-validated clinical nomograms to predict non-regional lymph node metastases: using (68)Ga-PSMA PET/CT as references. Front Oncol. 2021;11:658669. https://doi.org/10.3389/fonc.2021.658669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lenis AT, Pooli A, Lec PM, Sadun TY, Johnson DC, Lebacle C, et al. Prostate-specific membrane antigen positron emission tomography/computed tomography compared with conventional imaging for initial staging of treatment-naive intermediate- and high-risk prostate cancer: a retrospective single-center study. Eur Urol Oncol. 2022;5:544–52. https://doi.org/10.1016/j.euo.2020.08.012.

    Article  PubMed  Google Scholar 

  29. Barbato F, Fendler WP, Rauscher I, Herrmann K, Wetter A, Ferdinandus J, et al. PSMA-PET for the assessment of metastatic hormone-sensitive prostate cancer volume of disease. J Nucl Med. 2021;62:1747–50. https://doi.org/10.2967/jnumed.121.262120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Haran A. 611O Abiraterone acetate plus prednisolone for hormone-Naïve prostate cancer (PCa): long-term results from metastatic (M1) patients in the STAMPEDE randomised trial (NCT00268476). Ann Oncol. 2020;31(suppl_4):S507–49. https://doi.org/10.1016/annonc/annonc275.

    Article  Google Scholar 

  31. de Barros HA, van Beurden I, Droghetti M, Wilthagen EA, Ozman O, Bergman AM, et al. Role of local and/or metastasis-directed therapy in patients with hormone-sensitive M1a prostate cancer-a systematic review. Eur Urol Oncol. 2022. https://doi.org/10.1016/j.euo.2022.10.002.

    Article  PubMed  Google Scholar 

  32. Gandaglia G, Soligo M, Battaglia A, Muilwijk T, Robesti D, Mazzone E, et al. Which patients with clinically node-positive prostate cancer should be considered for radical prostatectomy as part of multimodal treatment? The impact of nodal burden on long-term outcomes. Eur Urol. 2019;75:817–25. https://doi.org/10.1016/j.eururo.2018.10.042.

    Article  PubMed  Google Scholar 

  33. Ali A, Hoyle A, Haran AM, Brawley CD, Cook A, Amos C, et al. Association of bone metastatic burden with survival benefit from prostate radiotherapy in patients with newly diagnosed metastatic prostate cancer: a secondary analysis of a randomized clinical trial. JAMA Oncol. 2021;7:555–63. https://doi.org/10.1001/jamaoncol.2020.7857.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors appreciate Prof. Xinyang Wang and Ke Xu from the Department of Urology, the First Affiliated Hospital of Xi’an Jiaotong University for helping with this paper.

Funding

This study was supported by the Clinical Application Research Grant of the First Affiliated Hospital of Xi’an Jiaotong University (to LL), the National Natural Science Foundation of China (NSFC 81202014 to KW), New-Star Young Scientists Programme in Shaanxi Province (2017KJXX-35 to KW), the Fundamental Research Funds for the Central Universities (to KW) and the Natural Science Foundation in Shaanxi Province (2023-JC-QN-0890 to JJF).

Author information

Author notes

  1. Zhangdong Jiang and Junjie Fan have contributed equally to this work (co-first authors)

Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, #277 Yanta West Road, Xi’an, 710061, Shaanxi, People’s Republic of China

    Zhangdong Jiang, Junjie Fan, Chaosheng Gan, Xiaoxin Dong, Guoqiang Gao, Dalin He, Lei Li & Kaijie Wu

  2. Department of Urology, Baoji Central Hospital, Baoji, Shaanxi, People’s Republic of China

    Junjie Fan

  3. Department of PET/CT Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, #277 Yanta West Road, Xi’an, 710061, Shaanxi, People’s Republic of China

    Zhuonan Wang & XiaoYi Duan

Authors
  1. Zhangdong Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Junjie Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chaosheng Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoxin Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guoqiang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhuonan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dalin He
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. XiaoYi Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kaijie Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Conceptualization: XYD and KJW; Methodology: ZDJ, JJF, XYD and KJW; Data collection and analysis: ZDJ, JJF, CSG, XXD, GQG, ZNW. Original draft preparation: ZDJ and JJF; Paper review and editing: DLH, LL, XYD and KJW. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to XiaoYi Duan or Kaijie Wu.

Ethics declarations

Ethics approval and consent to participate

All procedures performed in the study and involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This retrospective analysis was approved by the Institutional Review Board of the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China, and all participants signed an informed consent form.

Consent to publication

Written informed consent was obtained from the patient for publication of this study and accompanying images.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 2.

Fig. S1. The progression-free survival (PFS) difference between patients with and without non-regional lymph node (NRLN) metastases on 18F-PSMA-1007 PET/CT in patients with negative NRLN metastases on CI.

Additional file 2.

Table S1. Cox regression analysis for associations of clinicopathological parameters with PFS among 94 patients without NRLN metastases on CI.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, Z., Fan, J., Gan, C. et al. Impact of non-regional lymph node metastases accurately revealed on 18F-PSMA-1007 PET/CT in the clinical management of metastatic hormone-sensitive prostate cancer. EJNMMI Res 13, 64 (2023). https://doi.org/10.1186/s13550-023-01009-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13550-023-01009-x

Keywords