Targeted salvage lymphadenectomy in patients treated with radical prostatectomy with biochemical recurrence: complete biochemical response without adjuvant therapy in patients with low volume lymph node recurrence over a long-term follow-up

Background

Choline positron emission tomography/computed tomography (PET/CT) represents an option in restaging of prostate cancer patients with disease relapse after local treatment. The present study assess whether salvage resection of lymph node metastases detected on choline PET/CT imaging in prostate cancer patients with biochemical recurrence after radical prostatectomy can result in a long-term complete biochemical remission, without adjuvant therapy.

Methods

We analysed 13 patients with prostate specific antigen (PSA) recurrence (PSA median 1.64 ng/ml, range 0.5-9.55) after radical prostatectomy and suspicious lymph nodes (median 1; range 1–3) detected on [11C]choline and [18F]fluoroethylcholine PET/CT scans. An open salvage lymphadenectomy of positive lymph nodes in a PET/CT scan and nearby lymph nodes was carried out. We examined PSA outcome without adjuvant therapy; defined complete biochemical remission as PSA <0.01 ng/ml. Histological and PET/CT findings were compared.

Results

Ten of 11 patients with histologically confirmed lymph node metastases showed a PSA response. Three of ten patients with single lymph node metastases had a complete biochemical remission (median follow-up 72 months, range 31.0-83). In five cases with single lymph node metastasis PSA decreased <0.02 ng/ml. Histologically confirmed 13 of 16 metastasis suspicious lymph nodes. No lymph node metastases were detected in two patients. All of the additionally removed 30 lymph nodes were correctly negative.

Conclusions

This is the first confirmation of a complete biochemical remission after PET/CT guided secondary resection of a single lymph node metastasis in prostate cancer patients with biochemical recurrence after radical prostatectomy, over the long-term (>6.5 years), without adjuvant therapy. In order to improve these promising results, longer-term studies with more patients are required.     

Combined 18F‐fluorocholine and 18F‐fluoride positron emission tomography/computed tomography imaging for staging of high‐risk prostate cancer

Study Type – Diagnosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Positron emission tomography/computed tomography (PET/CT) with choline and fluoride for the detection of metastases in patients with prostate cancer have each been evaluated, with mixed results. Choline PET/CT has been evaluated against pelvic lymphadenectomy, generally with a low sensitivity but a high specificity; however, the study populations have been heterogenous. Fluoride PET/CT has been evaluated against other imaging methods, such as bone scan, single photon emission CT and MRI, and has been shown to have high specificity as well as sensitivity for bone metastases, but there are no studies with biopsy verification. This is the first study that evaluates the clinical use of both choline and fluoride PET/CT on the same patients in a well‐defined population of patients with high‐risk prostate cancer.

OBJECTIVE

• ? To investigate how often positron emission tomography/computed tomography (PET/CT) scans, with both ¹⁸F‐fluorocholine and ¹⁸F‐fluoride as markers, add clinically relevant information for patients with prostate cancer who have high‐risk tumours and a normal or inconclusive planar bone scan.

PATIENTS AND METHODS

• ? Patients with prostate cancer with prostate specific antigen (PSA) levels between 20 and 99 ng/mL and/or Gleason score 8–10 tumours, planned for treatment with curative intent based on routine staging with a negative or inconclusive bone scan, were further investigated with a ¹⁸F‐fluorocholine and a ¹⁸F‐fluoride PET/CT.
• ? None of the patients received hormonal therapy before the staging procedures were completed.

RESULTS

• ? For 50 of the 90 included patients (56%) one or both PET/CT scans indicated metastases.
• ? ¹⁸F‐fluorocholine PET/CT indicated lymph node metastases and/or bone metastases in 35 patients (39%).
• ? ¹⁸F‐fluoride PET/CT was suggestive for bone metastases in 37 patients (41%).
• ? In 18 patients (20%) the PET/CT scans indicated widespread metastases, leading to a change in therapy intent from curative to non‐curative.
• ? Of the patients with positive scans, 74% had Gleason score 8–10 tumours. Of the patients with Gleason score 8–10 tumours, 64% had positive scans.

CONCLUSIONS

• ? PET/CT scans with ¹⁸F‐fluorocholine and ¹⁸F‐fluoride commonly detect metastases in patients with high‐risk prostate cancer and a negative or inconclusive bone scan.
• ? For 20% of the patients the results of the PET/CT scans changed the treatment plan.

     

[18F]‐fluorocholine positron‐emission/computed tomography for lymph node staging of patients with prostate cancer: preliminary results of a prospective study

Study Type – Diagnostic (case series)
Level of Evidence 4

OBJECTIVES

To evaluate prospectively [¹⁸F]‐fluorocholine positron‐emission/computed tomography (FCH PET/CT) for lymph node staging of prostate cancer before intended curative therapy, and to determine whether imaging 15 or 60 min after radiotracer injection is preferable.

PATIENTS AND METHODS

In all, 25 consecutive patients with newly diagnosed prostate cancer (Gleason score >6, and/or a prostate‐specific antigen level of >10 ng/mL, and/or T3 cancer) were scanned before lymphadenectomy. Each patient was assessed twice with imaging, at 15 and 60 min after the injection with FCH. Images were compared with the results of histopathological examination of the surgically removed lymph nodes. Maximum standardized uptake values (SUV_max) at 15 and 60 min were also compared.

RESULTS

Histopathologically, metastases were present in removed lymph nodes from three patients. FCH PET/CT showed a high radiotracer uptake in four patients, the former three and a fourth. The sensitivity, specificity, positive and negative predictive value of FCH PET/CT for patient based lymph node staging of prostate cancer were 100%, 95%, 75% and 100%, respectively; the corresponding 95% confidence intervals were 29.2–100%, 77.2–99.9%, 19.4–99.4% and 83.9–100%, respectively. Values of SUV_max at early and late imaging were not significantly different.

CONCLUSIONS

This small series supports the use of FCH PET/CT as a tool for lymph node staging of patients with prostate cancer. Values of SUV_max at early and late imaging did not differ. However, larger prospective studies are needed to validate these findings.     

Imaging of prostate cancer with PET/CT and radioactively labeled choline derivates

PET- and PET/CT using [¹¹C]- and [¹⁸F]-labeled choline derivates are increasingly being used for imaging of prostate cancer. The value of PET- and PET/CT with [¹¹C]- and [¹⁸F]-labeled choline derivates in biochemical recurrence of prostate cancer has been examined in many studies and demonstrates an increasing importance. PET/CT, in comparison to PET, improves especially the lesion localization as well as characterization. Primary prostate cancer can be detected with moderate sensitivity using PET and PET/CT using [¹¹C]- and [¹⁸F]-labeled choline derivates—the differentiation between benign prostatic hyperplasia, prostatitis, or high-grade intraepithelial neoplasia (HGPIN) is not always possible. At the present time, [¹¹C]-choline PET/CT is not recommended in the primary setting but may be utilized in clinically suspected prostate cancer with repeatedly negative prostate biopsies, in preparation of a focused re-biopsy. Promising results have been obtained for the use of PET and PET/CT with [¹¹C]- and [¹⁸F]-labeled choline derivates in patients with biochemical recurrence. The detection rate of choline PET and PET/CT for local, regional, and distant recurrence in patients with a biochemical recurrence shows a linear correlation with PSA value at the time of imaging and reaches about 75% in patients with PSA > 3 ng/ml. Even at PSA values below 1 ng/ml, the recurrence can be diagnosed with choline PET/CT in approximately one-third of the patients. PET and PET/CT with [¹¹C]- and [¹⁸F]-choline derivates can be helpful in the clinical setting for choosing a therapeutic strategy in the sense of an individualized treatment: an early diagnosis of recurrence is crucial to the choice of optimal treatment. Especially important for the choice of treatment is the exact localization of the site of recurrence: local recurrence, recurrence as lymph node metastasis, or systemic recurrence, as it has direct influence on individual therapy. This article reviews the use of PET and PET/CT with [¹¹C]- and [¹⁸F]-labeled choline derivates in prostate cancer imaging with special emphasis on patients with biochemical recurrence. We briefly provide an overview of PET tracers for prostate cancer imaging, the rationale of using choline derivatives for prostate cancer imaging and discuss the contribution of choline PET/CT in patients suffering from prostate cancer with an emphasis on recurrent disease. Furthermore, we provide an outlook on future prospects of choline PET/CT imaging for therapy guidance and monitoring in the framework of therapy individualization.     

The Role of Choline Positron Emission Tomography/Computed Tomography in the Management of Patients with Prostate-Specific Antigen Progression After Radical Treatment of Prostate Cancer

Context

Choline positron emission tomography (PET)/computed tomography (CT) is a currently used diagnostic tool in restaging prostate cancer (PCa) patients with increasing prostate-specific antigen (PSA) after either radical prostatectomy (RP) or external-beam radiation therapy (EBRT). However, no final recommendations have been made on the use of this modality for patient management.

Objective

To critically analyse the current evidence for the use of choline PET/CT scanning in the management of patients with a progressive increase in PSA after radical treatment for PCa, evaluating its diagnostic accuracy in the detection of recurrences, the clinical predictors of positive PET/CT examinations, and the modalities’ role as a guide for tailored therapeutic strategies.

Evidence acquisition

Data on recently published (2003–2010) original articles, review articles, and editorials concerning the role of choline PET/CT in this scenario were analysed.

Evidence synthesis

The diagnostic accuracy of choline PET in detecting sites of PCa relapse has been investigated by several authors, and the overall reported sensitivity ranges between 38% and 98%. It has been demonstrated that choline PET technology's positive detection rate improves with increasing PSA values. The routine use of choline PET/CT cannot be recommended for PSA values <1 ng/ml. However, in addition to PSA serum value, PSA doubling time (PSA DT), and other clinical and pathologic features—including locally advanced tumour (pT3b–T4) or lymph node involvement at initial staging—should be considered to refer patients to choline PET/CT study. Choline PET/CT may be also proposed as a image guide either for experimental surgical or radiation therapy treatments.

Conclusions

According to the current available data, choline PET/CT plays a role in the management of biochemical relapse. Its accuracy is correlated to PSA value, PSA DT, and other pathologic features. Choline PET/CT may be proposed as a guide for individualised treatment of recurrence.     

18F-Fluoroethylcholine PET/CT Identifies Lymph Node Metastasis in Patients with Prostate-Specific Antigen Failure After Radical Prostatectomy but Underestimates Its Extent

Background

The detection of lymph node metastases (LNMs) is one of the biggest challenges in imaging in urology.

Objective

To evaluate the accuracy of combined 18F–fluoroethylcholine (FEC) positron emission tomography (PET)/computed tomography (CT) in the detection of LNMs in prostate cancer (PCa) patients with rising prostate-specific antigen (PSA) level after radical prostatectomy.

Design, settings, and participants

From June 2005 until November 2011, 56 PCa patients with biochemical recurrence after radical prostatectomy underwent bilateral pelvic and/or retroperitoneal lymphadenectomy based on a positive 18F-FEC PET/CT scan.

Outcome measurements and statistical analysis

The findings of PET/CT were compared with the histologic results.

Results and limitations

Median PSA value at the time of 18F-FEC PET/CT analysis was 6.0 ng/ml (interquartile range: 1.7–9.4 ng/ml). In 48 of 56 (85.7%) patients with positive 18F-FEC PET/CT findings, histologic examination confirmed the presence of PCa LNMs. Of 1149 lymph nodes that were removed and histologically evaluated, 282 (24.5%) harbored metastasis. The mean number of lymph nodes removed per surgical procedure was 21 (standard deviation: ±18.3). A lesion-based analysis yielded 18F-FEC PET/CT sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 39.7%, 95.8%, 75.7%, and 83.0%, respectively.A site-based analysis yielded sensitivity, specificity, PPV, and NPV of 68.4%, 73.3%, 81.3%, and 57.9%, respectively. Patients with negative PET/CT did not undergo surgery, thus sensitivity, specificity, and negative predictive value on a patient basis could not be calculated.

Conclusions

A positive 18F-FEC PET/CT result correctly predicted the presence of LNM in the majority of PCa patients with biochemical failure after radical prostatectomy but did not allow for localization of all metastatic lymph nodes and therefore was not adequately accurate for the precise estimation of extent of nodal recurrence in these patients.     

18F-fluorocholine PET/CT compared with extended pelvic lymph node dissection in high-risk prostate cancer

Purpose

To compare ¹⁸F-fluorocholine positron-emission tomography/computed tomography (PET/CT) with extended pelvic lymph node dissection (ePLND) for the detection of lymph node metastases in a large cohort of patients with high-risk prostate cancer.

Materials and methods

Patients with prostate-specific antigen levels between 20 and 99 ng/mL and/or Gleason score 8–10 cancers, planned for treatment with curative intent following a negative or inconclusive standard bone scan, were investigated with ¹⁸F-fluorocholine PET/CT followed by an ePLND. None of the patients received hormonal therapy prior to these staging procedures. Results for PET/CT were compared on a per-patient basis with histopathology from ePLND. Sensitivity, specificity, positive and negative predictive values were calculated.

Results

PET/CT detected a total of 76 suspected lymph node metastases and four suspected bone metastases in 33 (29 %) of the 112 included patients. Of these, 35 suspected lymph node metastases, only within the anatomical template area of an ePLND, were found in 21 of the patients. Histopathology of the ePLND specimens detected 117 lymph node metastases in 48 (43 %) of the 112 patients. Per-patient sensitivity, specificity, positive and negative predictive values for ¹⁸F-fluorocholine PET/CT for lymph node metastases within the ePLND template were 0.33, 0.92, 0.76 and 0.65, respectively. Only 11 patients had lymph nodes larger than 10 mm that would have been reported by CT alone.

Conclusions

¹⁸F-fluorocholine PET/CT detects lymph node metastases in a significant proportion of patients with high-risk prostate cancer with a high specificity, but low sensitivity.     

68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography for patients with favorable intermediate-risk prostate cancer

IntroductionCurrent guidelines do not support the use of pretreatment imaging in patients with favorable intermediate-risk prostate cancer. ⁶⁸Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is more accurate than conventional imaging for preoperative staging. We aimed to evaluate whether pretreatment ⁶⁸Ga-PSMA PET/CT is beneficial for identifying pathological lymph node involvement (LNI) and adverse pathology among patients with favorable intermediate-risk prostate cancer.MethodsWe reviewed 88 patients with favorable intermediate-risk prostate cancer who underwent ⁶⁸Ga-PSMA PET/CT prior to radical prostatectomy and lymph node dissection from 2016–2020. The primary endpoint was the presence of pathological LNI. Association between pretreatment characteristics and outcomes were evaluated.ResultsPreoperative ⁶⁸Ga-PSMA PET/CT showed suspicious uptake in lymph nodes in 4/88 patients (5%), hence, 20 patients would need to be scanned to identify a patient with a positive lymph node on imaging. Two patients had pathological LNI, only one of whom showed ⁶⁸Ga-PSMA PET/CT uptake prior to surgery. The sensitivity, specificity, positive predictive value, and negative predictive values of ⁶⁸Ga-PSMA PET/CT for identifying LNI were 50%, 97%, 25%, and 99%, respectively. After surgery, four patients had evidence of prostate-specific antigen (PSA) persistence. The rate of PSA persistence was higher among patients with LNI on preoperative ⁶⁸Ga-PSMA PET/CT (2/4, 50% vs. 2/84, 2%, p=0.009).ConclusionsPreoperative imaging of favorable intermediate-risk prostate cancer patients using ⁶⁸Ga-PSMA PET/CT showed a low yield for identifying patients at higher risk. Consistent with current guidelines, our findings do not support the routine use of PET/CT in this group of patients. Future prospective studies are needed to validate our findings.     

Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography

Background

The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging.

Objective

To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP.

Design, setting, and participants

Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan.

Intervention

Patients underwent salvage lymph node dissection (LND).

Measurements

Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively.

Results and limitations

Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA <4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR <24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p = 0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p = 0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR = 2.92; p = 0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p = 0.02), higher number of positive lymph nodes (HR: 1.04; p = 0.006), and complete BR to salvage LND (HR: 0.31; p = 0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses.

Conclusions

Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan. Biochemical response after surgery can be achieved in a consistent proportion of patients. Although most patients invariably progressed to BCR after surgery at longer follow-up, 35% of patients showed the absence of CR at 5 yr.     

Diagnostic performance of 18F-DCFPyL positron emission tomography/computed tomography for biochemically recurrent prostate cancer and change-of-management analysis

IntroductionConventional imaging (CI) performs poorly to identify sites of disease in biochemically recurrent prostate cancer. ⁶⁸Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) is most studied but has a very short half-life. This study reports the diagnostic performance of the novel prostate-specific membrane antigen (PSMA) radiotracer ¹⁸F-DCFPyL using real-life data and tumor board simulation to estimate the impact of ¹⁸F-DCFPyL PET on patient management.MethodsNinety-three ¹⁸F-DCFPyL PET/CT scans performed for patients previously treated for prostate cancer with a rising prostate-specific antigen (PSA) were retrospectively compared to contemporary CI and clinical imaging and PSA followups. A chart review was performed to document prior imaging, pathology results, serial serum PSA measurements, and other pertinent clinical data. Clinical utility of ¹⁸F-DCFPyL PET was measured using a simulated tumor board formed by three physicians with extensive prostate cancer experience deciding on management with and without knowledge of PET/CT results.ResultsAt median PSA 2.27 (interquartile rage [IQR] 5.27], 82% of ¹⁸F-DCFPyL PET/CT demonstrated at least one site of disease: non-regional lymph nodes (37% of scans), regional lymph node metastases (28%), local recurrence (27%), and bone metastases (20%), with higher PET positivity at higher PSA. Compared to ¹⁸F-DCFPyL PET/CT, CI showed overall poor performance, with accuracy below 20% for all extent of disease. PET/CT changed management in 44% of cases. The most frequent scenario was a radical change from initiating androgen deprivation therapy (ADT) to stereotactic body radiotherapy (SBRT) of oligo-lesional disease. In univariate and multivariate analysis, no patient characteristic could predict change of management by PET/CT results.Conclusions¹⁸F-DCFPyL significantly outperforms CI in recurring prostate cancer and is likely to impact management.     

Percentage of positive biopsies predicts lymph node involvement in men with low‐risk prostate cancer undergoing radical prostatectomy and extended pelvic lymphadenectomy

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? The current retrospective study evaluates predictive clinical parameters associated with lymph node metastasis in a homogeneous cohort of 499 men with low‐risk prostate cancer who underwent radical prostatectomy. Low‐risk profile and <50% of biopsies involved with cancer are strong predictors of metastasis‐free lymph nodes so that patients do not have to undergo extended pelvic lymphadenectomy.

OBJECTIVE

To evaluate preoperative predictive risk factors associated with lymph node metastases (LNM) in a cohort of low‐risk prostate cancer (PCA) patients.

PATIENTS AND METHODS

The charts of 499 patients were retrospectively reviewed to identify prognostic risk factors for the presence of LNM. Pathohistological data and Gleason score of the radical prostatectomy (RP) specimen, number of removed nodes, number of positive lymph nodes, and anatomical distribution of LNM were tabulated and evaluated. A correlation between clinical stage, preoperative serum prostate‐specific antigen (PSA), biopsy Gleason score, number of biopsies taken, percentage of positive biopsies and the presence of LNM were calculated. All 499 men underwent retropubic RP and extended pelvic lymphadenectomy (EPLND).

RESULTS

LNM were identified in 29 (5.8%) patients. A prediction model based on clinical stage, PSA, and biopsy Gleason score had a predictive accuracy of 79.2%. The addition of number of positive biopsies and % positive cores improved its predictive accuracy to 81.5% and 87.8%, respectively. The predicted frequency of LNM by the original nomogram was 7.4% and differed by less than 3% with the actual observation of LNM. The predictive accuracy of the nomogram was 81.5% as compared with 87.8% of the prediction model of this study.

CONCLUSIONS

The percentage of positive cores involved with PCA is the most reliable predictor of LNM and indicates the need for EPLND. The Briganti nomogram has been validated and a general applicability for predicting the presence of LNM was proven.     

[<Superscript>11</Superscript>C]choline PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy

Objective  

To evaluate [¹¹C]choline positron emission tomography/computed tomography ([¹¹C]choline PET/CT) for the detection of a biochemical recurrence of prostate cancer after radical prostatectomy.     

Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new non-muscle-invasive bladder cancer: validation across time and place and recommendation for benchmarking

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Staging of patients with prostate cancer is the cornerstone of treatment. However, after curative intended therapy a high portion of patients relapse with local and/or distant recurrence. Therefore, one may question whether surgical lymph node dissection (LND) is sufficiently reliable for staging of these patients. Several imaging methods for primary LN staging of patients with prostate cancer have been tested. Acceptable detection rates have not been achieved by CT or MRI or for that matter with PET/CT using the most common tracer fluoromethylcholine (FCH). Other more recent metabolic tracers like acetate and choline seem to be more sensitive for assessment of LNs in both primary staging and re‐staging. However, previous studies were small. Therefore, we assessed the value of [¹⁸F]FCH PET/CT for primary LN staging in a prospective study of a larger sample and with a ‘blinded’ review. After a study period of 3 years and >200 included patients, we concluded that [¹⁸F]FCH PET/CT did not reach an optimal detection rate compared with LND, and, therefore, it cannot replace this procedure. However, we did detect several bone metastases with [¹⁸F]FCH PET/CT that the normal bone scans had missed, and this might be worth pursuing.

OBJECTIVES

• ? To assess the value of [¹⁸F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging of prostate cancer.
• ? To evaluate if FCH PET/CT can replace LN dissection (LND) for LN staging of prostate cancer, as about one‐third of patients with prostate cancer who receive intended curative therapy will have recurrence, one reason being undetected LN involvement.

PATIENTS AND METHODS

• ? From January 2008 to December 2010, 210 intermediate‐ or high‐risk patients had a FCH PET/CT scan before regional LND.
• ? After dissection, the result of histological examination of the LNs (gold standard) was compared with the result of FCH PET/CT obtained by ‘blinded review’.
• ? Sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of FCH PET/CT were measured for detection of LNe metastases.

RESULTS

• ? Of the 210 patients, 76 (36.2%) were in the intermediate‐risk group and 134 (63.8%) were in the high‐risk group. A medium (range) of 5 (1–28) LNs were removed per patient.
• ? Histological examination of removed LNs showed metastases in 41 patients. Sensitivity, specificity, PPV, and NPV of FCH PET/CT for patient‐based LN staging were 73.2%, 87.6%, 58.8% and 93.1%, respectively.
• ? Corresponding values for LN‐based analyses were 56.2%, 94.0%, 40.2%, and 96.8%, respectively.
• ? The mean diameter of the true positive LN metastases was significantly larger than that of the false negative LNs (10.3 vs 4.6 mm; P < 0.001).
• ? In addition, FCH PET/CT detected a high focal bone uptake, consistent with bone metastases, in 18 patients, 12 of which had histologically benign LNs.

CONCLUSIONS

• ? Due to a relatively low sensitivity and a correspondingly rather low PPV, FCH PET/CT is not ideal for primary LN staging in patients with prostate cancer.
• ? However, FCH PET/CT does convey important additional information otherwise not recognised, especially for bone metastases.

     

68Ga-PSMA PET/CT在前列腺癌术前诊断及手术策略制订中的应用

目的评估⁶⁸Ga标记的前列腺特异性膜抗原(⁶⁸Ga-PSMA)PET/CT对前列腺癌的诊断效能,并探讨⁶⁸Ga-PSMA PET/CT对术前制订保留血管神经束(NVB)和淋巴结清扫策略的指导作用。方法回顾性分析2018年6月至2019年10月中国医学科学院肿瘤医院行⁶⁸Ga-PSMA PET/CT检查的46例初诊疑似前列腺癌患者的临床资料。中位年龄66.50(60.00,69.25)岁,中位前列腺特异性抗原(PSA)值15.97(8.58,33.10)ng/ml。46例中,41例⁶⁸Ga-PSMA PET/CT检查诊断为肿瘤,6例诊断有淋巴结转移;5例诊断为前列腺增生或前列腺炎。46例中40例同期行mpMRI检查,33例诊断为肿瘤,6例诊断有淋巴结转移;46例中17例同期行^11C-胆碱PET/CT检查,12例诊断为肿瘤,4例诊断有淋巴结转移。41例PSMA-PET/CT诊断为前列腺癌的患者中,高危22例,中危19例;其中37例行mpMRI检查,15例行^11C-胆碱PET/CT检查。41例均行根治性前列腺切除术。根据⁶⁸Ga-PSMA PET/CT显示的肿瘤位置,术前制订NVB处理策略:若肿瘤邻近前列腺单侧包膜,则保留健侧的NVB;若肿瘤局限于前列腺内,则保留双侧NVB。共16例保留了NVB(单侧6例,双侧10例)。对中高危组患者常规行淋巴结清扫。采用配对χ²检验或Fisher精确检验比较⁶⁸Ga-PSMA PET/CT、mpMRI、^11C-胆碱PET/CT对病灶检出的敏感性和特异性。采用Spearman相关分析检测⁶⁸Ga-PSMA PET/CT的SUV_max值与Gleason评分和治疗前PSA值的相关性。结果 41例行根治术患者术后病理确诊为前列腺癌,手术切缘均未见癌组织;中位Gleason评分8(7,9)分;病理分期20例≤pT_2c期,21例≥pT₃期;7例淋巴结阳性(11枚阳性淋巴结)。术后30 d内7例(17.1%)发生并发症,Clavien-Dindo分级均≤2级。41例术后随访中位时间16(12,20)个月,术后1、6、12个月分别有19例(46.3%)、39例(95.1%)、41例(100.0%)恢复控尿。5例未行手术的患者中,4例行抗生素治疗后PSA下降;1例PSA未下降者行穿刺活检,病理未见癌。⁶⁸Ga-PSMA PET/CT诊断前列腺癌的敏感性为100.0%(41/41),显著优于^11C-胆碱PET/CT[80.0%(12/15),P=0.016]和mpMRI[83.7%(31/37),P=0.009];特异性为100.0%(5/5),与^11C-胆碱PET/CT[100.0%(2/2),P=1.000]和mpMRI [33.3%(1/3),P=0.107]的差异均无统计学意义。41例中,⁶⁸Ga-PSMA PET/CT诊断淋巴结转移的敏感性[71.4%(5/7)]与^11C-胆碱PET/CT的差异无统计学意义[75.0%(3/4),P=1.000],与mpMRI的差异有统计学意义[16.7%(1/6),P=0.016]。Gleason评分≥8分与<8分患者⁶⁸Ga-PSMA PET/CT的原发灶SUV_max值分别为19.60(9.58,24.38)与8.55(5.18,12.88);治疗前PSA值≥20 ng/ml与<20 ng/ml患者的SUV_max值分别为19.40(13.00,23.5)与8.40(5.35,13.95),差异均有统计学意义(P<0.05)。结论 ⁶⁸Ga-PSMA PET/CT对前列腺癌原发病灶诊断的敏感性高、特异性高,术前可根据PSMA PET/CT显示的肿瘤位置,制订是否保留NVB的处理策略;但其对淋巴结转移灶诊断的敏感性还不足以指导术前制订淋巴结清扫策略。     

Evaluation of fluorodeoxyglucose positron‐emission tomography with computed tomography for staging of urothelial carcinoma

Study Type – Diagnostic (case series)
Level of Evidence 4

OBJECTIVE

To investigate the role of ¹⁸F‐fluorodeoxyglusose positron‐emission tomography (FDG‐PET), combined with computed tomography (CT) and forced diuresis, in the staging and follow‐up of urothelial carcinoma (UC).

PATIENTS AND METHODS

We recruited 44 patients with muscle‐invasive urothelial bladder cancer (UBC) before radical cystectomy (RC), 19 under follow‐up after RC and seven after systemic chemotherapy. For those who had RC, histopathology was used as the reference standard to compare the sensitivity and specificity of FDG‐PET/CT and standard CT in detecting UBC and pelvic lymph node metastasis. Furthermore, 36 patients with ≥6 months of follow‐up imaging were considered to describe the progression of UC and extrapelvic positive FDG‐PET/CT images.

RESULTS

For the detection of primary UBC, FDG‐PET/CT was slightly more sensitive than CT (85% vs 77%) but less specific (25% vs 50%). For the detection of pelvic node metastasis FDG‐PET/CT was more sensitive than CT (57% vs 33%) with a specificity of 100% for both imaging techniques. In 20 patients, extrapelvic FDG‐PET/CT images showed suspected disease at the first evaluation. UC progressed in nine of the 10 patients who had synchronous multiple PET‐positive retroperitoneal or mediastinal lymph nodes, and in only two of the nine with unique hyperactive lesions in the lung. FDG‐PET/CT also detected a pT1G3 UC of the renal pelvis and all bone metastases detected by bone scintigraphy.

CONCLUSIONS

FDG‐PET/CT could replace standard CT and bone scintigraphy in the presurgical staging and monitoring of patients with UC after surgery or chemotherapy.     

68Ga-PSMA-11 PET/TC en la recidiva bioquímica oculta del carcinoma de próstata,con 18F-Colina PET/TC negativa. Valoración preliminar de su uso clínico

ObjectiveTo assess the clinical usefulness of ⁶⁸Ga-PSMA PET/CT studies in patients with occult biochemical recurrence of prostate carcinoma, with negative or inconclusive radiologic and 18F-Choline PET/CT imaging studies.Material and methodsRetrospective observational and diagnostic accuracy. The first 14 patients with a history of prostate carcinoma, treated with curative intent and presenting suspicion of biochemical recurrence with low PSA values (< 3 ng/ml) were selected. Imaging studies, prostate ultrasound, pelvic CT and/or MRI were negative, and all of them had a negative or inconclusive 18F-Choline PET/CT.All patients were referred to ⁶⁸Ga-PSMA-11 PET/CT. Protocol: Dose 2.2 MBq/kg. 20 mg furosemide at start. PET/CT images from skull base to proximal third of thighs at 60 min, and late images at 3 hours if needed.ResultsThe ⁶⁸Ga-PSMA-11 PET/CT was able to localize the occult biochemical recurrence in 9 of the 14 patients (64.2%), and it affected the therapeutic attitude in all of them.Four patients (28.5%) obtained a negative or inconclusive ⁶⁸Ga-PSMA-11 PET/CT and continued under vigilant approach with PSA controls and imaging studies according to the clinical guidelines. These patients had the lowest PSA values (less than 1 ng/ml).One of the ⁶⁸Ga-PSMA-11 PET/CT studies was inconclusive, reporting the presence of a doubtful right iliac adenopathy.Conclusión⁶⁸Ga-PSMA-11 PET/CT allows an early diagnosis, with low PSA values, of occult biochemical recurrence of prostate carcinoma, even in patients with negative 18F-Choline PET/CT.     

Diagnostic efficacy of [11C]choline positron emission tomography/computed tomography compared with conventional computed tomography in lymph node staging of patients with bladder cancer prior to radical cystectomy

Background

Current imaging techniques are of limited value for lymph node (LN) staging in bladder cancer (BCa) patients scheduled for radical cystectomy (RC).

Objective

Evaluate the diagnostic efficacy of [11C]choline positron emission tomography in combination with computed tomography (PET/CT) for LN staging of patients with BCa scheduled for RC and compare that efficacy with the diagnostic efficacy of CT and the gold standard of histopathologic evaluation.

Design, setting, and participants

From June 2004 to May 2007, 44 patients with localized BCa were staged with [11C]choline PET with low-dose CT for attenuation correction and simultaneous intravenous and rectal contrast-enhanced diagnostic CT before RC and pelvic lymph node dissection (PLND). LNs were dissected from the internal and external iliac arteries up to the origin of the inferior mesentery artery according to a template with 14 predefined anatomic fields.

Intervention

Diagnostic [11C]choline PET/CT before RC and regional LN dissection.

Measurements

Histopathologic findings of resected LN were correlated with the results of [11C]choline PET/CT and CT alone in a patient- and field-based manner. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [11C]choline PET/CT and CT were assessed.

Results and limitations

LN metastases were found in 12 of 44 patients (27%). On patient-based analysis, sensitivity, specificity, PPV, NPV, and accuracy for [11C]choline PET/CT were calculated as 58%, 66%, 39%, 81%, and 64%, respectively; and for CT the calculated percentages were 75%, 56%, 39%, 86%, and 61%, respectively. Twenty-five of 471 dissected LN fields (5%) showed metastases. On field-based analysis, sensitivity, specificity, PPV, NPV, and accuracy for [11C]choline PET/CT were 28%, 95%, 21%, 96%, and 91%, respectively; for CT, the calculated percentages were 39%, 92%, 20%, 96%, and 90%, respectively. Limitations of this study are small patient number and the fact that not all patients underwent extensive PLND.

Conclusions

In patients with BCa who were scheduled for RC, preoperative LN staging with [11C]choline PET/CT was not able to improve diagnostic efficacy compared with conventional CT alone.     

<Superscript>99m</Superscript>Tc-HDP bone scintigraphy and <Superscript>18</Superscript>F-sodiumfluoride PET/CT in primary staging of patients with prostate cancer

Introduction/Aim

Correct staging of patients with prostate cancer is important for treatment planning and prognosis. Although bone scintigraphy with ^99mTc-phosphonates (BS) is generally advised for staging by guidelines in high risk prostate cancer, this imaging technique is hampered by a high rate of inconclusive results and moderate accuracy. Potentially better imaging techniques for detection of bone metastases such as ¹⁸F-sodiumfluoride PET/CT (NaF PET/CT) are therefore being evaluated. In this observational cohort study we evaluate the performance and clinical impact of both BS and NaF PET/CT in primary staging of patients with prostate cancer.

Methods

The first of two cohorts consisted of patients who received a BS while the second included patients who received a NaF PET/CT for primary staging of prostate cancer. For both cohorts the number of positive, negative and equivocal findings, calculated diagnostic performance of the imaging modality in terms of sensitivity and specificity, as well as the impact on clinical management were studied. The ranges of the diagnostic performance were calculated both assuming that equivocal findings were positive and assuming that they were negative for bone metastases. For the NaF PET/CT cohort the number of patients with signs of lymph node metastases on low dose CT were also recorded, including the impact of these findings on clinical management.

Results

One-hundred-and-four patients underwent NaF PET/CT, whereas 122 patients underwent BS. Sensitivities of 97–100 and 84–95% and specificities of 98–100 and 72–100% were found on a patient basis for detection of bone metastases with NaF PET/CT and BS, respectively. Equivocal findings warranted further diagnostic procedures in 2% of the patients in the NaF cohort and in 16% in the BS cohort. In addition NaF PET/CT demonstrated lymph node metastases in 50% of the included patients, of which 25% showed evidence of lymph node metastases only.

Conclusion

Our data indicate better diagnostic performance of NaF PET/CT compared to BS for detection of bone metastases in primary staging of prostate cancer patients. Less equivocal findings are encountered with NaF PET/CT. Moreover, NaF PET/CT has additional value over BS since lymph node metastases are encountered frequently.

     

Impact of total PSA, PSA doubling time and PSA velocity on detection rates of 11C-Choline positron emission tomography in recurrent prostate cancer

Purpose

To evaluate the effect of total PSA (tPSA) and PSA kinetics on the detection rates of ¹¹C-Choline PET in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) or external beam radiotherapy (EBRT).

Methods

We included 185 patients with BCR after RP (PSA >0.2 ng/ml) or after EBRT (ASTRO definition). After injection of 400 MBq ¹¹C-Choline i.v., a scan was made using the ECAT HR + PET camera with CT fusion images or Siemens mCT PET/CT. Biopsy-proven histology, confirmative imaging (CT or bone scan) and/or clinical follow-up (PSA) were used as composite reference. Statistical analysis was performed using PASW Statistics 18.

Results

¹¹C-Choline PET was positive in 124/185 cases (65 %) (in 22/61 (36 %) after RP, 102/124 (82 %) after EBRT). In 79 patients a local recurrence was identified, and 45 patients showed locoregional metastases on PET/CT. In 20 cases a proven false-negative PET scan was observed. Positive PET scans were confirmed by histology in 87/124 (70 %) cases, by confirmatory imaging in 34/124 (28 %) and by clinical follow-up after salvage treatment in 3 (2 %) cases. The ROC analysis to detect a recurrence showed significant difference in area under the curve (AUC) of tPSA 0.721(p < 0.001) and PSA velocity 0.730 (p < 0.001). PSA doubling time showed no significant difference with an AUC of 0.542 (p = 0.354). Detection rates are <50 % in tPSA <2 ng/ml and/or PSA velocity <1 ng/ml/year.

Conclusions

Total serum PSA and PSA velocity have significant effect on the detection rates of ¹¹C-Choline PET/CT in men with a BCR after RP or EBRT.     

The accuracy of integrated PET-CT compared with dedicated PET alone for the staging of patients with nonsmall cell lung cancer

Background

The treatment of patients with nonsmall cell lung cancer (NSCLC) is determined by the stage. We evaluated the accuracy of staging using integrated positron emission tomography (PET) and computed tomography (CT) and compared it with dedicated PET visually correlated with CT scan.

Methods

A prospective blinded trial was performed on a consecutive series of patients with NSCLC. Patients underwent integrated PET-CT scanning with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG-18). A radiologist assigned the T, N and M status. No sooner than 2 weeks the same radiologist read the dedicated PET alone, without the integrated CT images and a T, N and M status was assigned again. The most recent CT scan was available and visually correlated with both studies. All patients underwent biopsies of suspicious N2 or N3 lymph node or distant metastases and if negative, pulmonary resection with lymphadenectomy was performed.

Results

There were 129 patients. Integrated PET-CT is a better predictor than PET for all stages of cancer and achieved statistical significance for stage I (52% versus 33%, p = 0.03) and for stage II (70% versus 36%, p = 0.04). It also is a better overall predictor for T status (70% versus 47%, p = 0.001) and the N status (78% versus 56%, p = 0.008). Nodal analysis shows that integrated PET-CT was more accurate for the total N2 nodes (96% versus 93%, p = 0.01) and for the total N1 nodes (90% versus 80%, p = 0.001). It was also more sensitive, specific, and had a higher positive predictive value for both N2 and N1 nodes (p < 0.05 for all). Integrated PET-CT is significantly more sensitive at the 4R, 5, 7, 10L and 11 stations and more accurate at the 7 and 11 lymph nodes stations than dedicated PET.

Conclusions

Integrated PET-CT using FDG-18 better predicts stage I and II disease as well as the T and N status of patients with NSCLC when compared with dedicated PET alone. It is more accurate at some nodal stations but still only achieves an accuracy of 96% and 90% for the N2 and N1 nodes, respectively.