Background
Despite its high specificity, PSMA PET/CT has a moderate to low sensitivity of 40–50% for pelvic lymph node detection, implicating that a negative PSMA PET/CT cannot rule out lymph node ...metastases. This study investigates a strategy of implementing PSMA PET/CT for initial prostate cancer staging and treatment planning compared to conventional diagnostics. In this PSMA PET/CT strategy, a bilateral extended pelvic lymph node dissection (ePLND) is only performed in case of a negative PSMA PET/CT; in case of a positive scan treatment planning is solely based on PSMA PET/CT results.
Method
A decision table and lifetime state transition model were created. Quality-adjusted life years and health care costs were modelled over lifetime.
Results
The PSMA PET/CT strategy of treatment planning based on initial staging with
68
GaGa-PSMA-11 PET/CT results in cost-savings of €674 and a small loss in quality of life (QoL), 0.011 QALY per patient. The positive effect of
68
GaGa-PSMA-11 PET/CT was caused by abandoning both an ePLND and unnecessary treatment in iM1 patients, saving costs and resulting in higher QoL. The negative effect was caused by lower QoL and high costs in the false palliative state, due to pN1
lim
patients (≤ 4 pelvic lymph node metastases) being falsely diagnosed as iN1
ext
(> 4 pelvic lymph node metastases). These patients received subsequently palliative treatment instead of potentially curative therapy.
Conclusion
Initial staging and treatment planning based on
68
GaGa-PSMA-11 PET/CT saves cost but results in small QALY loss due to the rate of false positive findings.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemically recurrent prostate cancer (BCR), mostly using gallium-68 (
168
Ga)-labelled radiotracers. ...Alternatively, fluorine-18 (
18
F)-labelled PSMA tracers are available, such as
18
F-DCFPyL, which offer enhanced image quality and therefore potentially increased detection of small metastases. In this study we evaluate the lesion detection efficacy of
18
F-DCFPyL PET/CT in patients with BCR and determine the detection efficacy as a function of their PSA value.
Methods
A total of 248 consecutive patients were evaluated and underwent scanning with
18
F-DCFPyL PET/CT for BCR between November 2016 and 2018 in two hospitals in the Netherlands. Patients were examined after radical prostatectomy (52%), external-beam radiation therapy (42%) or brachytherapy (6%). Imaging was performed 120 min after injection of a median dose of 311 MBq
18
F-DCFPyL.
Results
In 214 out of 248 PET/CT scans (86.3%), at least one lesion suggestive of cancer recurrence was detected (‘positive scan’). Scan positivity increased with higher PSA values: 17/29 scans (59%) with PSA values <0.5 ng/ml; 20/29 (69%) with PSA 0.5 to <1.0 ng/ml; 35/41 (85%) with PSA 1.0 to <2.0 ng/ml; 69/73 (95%) with PSA 2.0 to <5.0 ng/ml; and 73/76 (96%) with PSA ≥5.0 ng/ml. Interestingly, suspicious lesions outside the prostatic fossa were detected in 39–50% of patients with PSA <1.0 ng/ml after radical prostatectomy (i.e. candidates for salvage radiotherapy).
Conclusion
18
F-DCFPyL PET/CT offers early detection of lesions in patients with BCR, even at PSA levels <0.5 ng/ml. These results appear to be comparable to those reported for
68
Ga-PSMA and
18
F-PSMA-1007, with potentially increased detection efficacy compared to
68
Ga-PSMA for patients with PSA <2.0.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Purpose
Fluorine-18 (
18
F) prostate–specific membrane antigen (PSMA) 1007 (
18
F-PSMA-1007) is a radiotracer used in prostate cancer (PCa) staging. So far, no large histopathological validation ...study has been conducted. The objective was to determine diagnostic accuracy of
18
F-PSMA-1007 PET/CT compared to histopathological results of extended pelvic lymph node dissection (ePLND) in men with intermediate- or high-risk PCa.
Methods
Men with newly confirmed intermediate- or high-risk PCa were prospectively enrolled in the Molecular Imaging
18
F-PSMA-1007 PET/CT for lymph Node sTaging in primary PCa (MINT) trial. PET/CT images were read by two nuclear medicine physicians. Diagnostic accuracy was evaluated by histopathology of template resections. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) for LNI detection of
18
F-PSMA-1007 PET/CT were calculated.
Results
Ninety-nine men were evaluated; 30.3% showed histologically confirmed LNI. Median number of resected nodes was 22 (IQR 17–28). Patient-based sensitivity, specificity, PPV, and NPV were 53.3% (95% CI 34.3–71.7%), 89.9% (95% CI 80.2–95.8%), 69.6% (95% CI 51.2–83.3%), and 81.6% (95% CI 75.0–86.8%), respectively. Template-based sensitivity was 12.9% (95% CI 5.7–23.9%), specificity 97.7% (95% CI 96.6–98.5%), PPV 23.5% (95% CI 12.7–39.5%), and NPV 95.3% (95% CI 94.9–95.7%).
Conclusion
18
F-PSMA-1007 PET/CT showed high specificity but moderate to low sensitivity for LNI detection in intermediate- and high-risk PCa. It cannot replace ePLND for staging. Additional studies are needed to determine exact scan indications in lymph node staging for the primary diagnostic pathway in intermediate- or high-risk PCa.
Trial registry
December 12, 2018, Netherlands Trial Registry, NTR7670 (
https://www.trialregister.nl/trial/7428
).
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Accuracy of blind intra-articular injections for the shoulder is rather low. It is unclear whether accurate injections for capsulitis of the shoulder are more effective than inaccurate injections.
It ...has been hypothesized that a squishing sound following an intra-articular injection with a mixture of air and fluid means that the injection was accurately placed and that the efficacy of accurately placed injections is greater than that of inaccurate injections. The aim of the present study was to test the hypothesis that a squishing sound following an injection predicts a better clinical result.
Files were selected of patients with capsulitis of the shoulder, who were treated with an intra-articular injection containing a mixture of triamcinolone, lidocaine, and air. After the injection, the shoulder was moved to determine whether a squishing sound could be produced. Efficacy was measured after two weeks according to the Patient Global Impression of Change scale. Differences in efficacy between injections with and without a squishing sound were expressed as an odds ratio.
Sixty-one patients were selected. Squishing was heard after 47 injections (77%). Two weeks after the injection, a positive outcome was reported by 49 patients (80%). When squishing was heard, the effect was positive in 42 of the 47 patients (89%) and when no squishing was heard, the effect was positive in 7 of the 14 patients (50%). The odds ratio was 8.4 (95% CI 2.1-34.0; p= 0.003).
Efficacy of injections with a mixture of triamcinolone, lidocaine, and air for capsulitis of the shoulder is significantly greater when a squishing sound was heard after the injection. We hypothesize that squishing is related to accuracy and accuracy to efficacy. A future study with X-ray arthrography is needed to verify both hypotheses.
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DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Prostate-specific membrane antigen radioligand therapy (PSMA-RLT) is a novel treatment for castration-resistant prostate cancer (mCRPC). While the majority of patients responds to PSMA-RLT, with ...10-15% having an exceptional response, approximately 30% of patients is unresponsive to PSMA-RLT. The molecular underpinning may in part explain these varying responses. This study investigated alterations in DNA damage repair (DDR) genes in tumour biopsies and their association with response to PSMA-RLT.
A predefined retrospective cohort study was performed in mCRPC patients of whom the tumours had undergone next-generation sequencing of 40 DDR genes and received Lu-177-PSMA and/or Ac-225-PSMA-RLT. The primary outcome of this study was to compare the progression free survival (PFS) after PSMA-RLT for patients with and without pathogenic DDR aberrations in their tumour. Secondary outcomes were prostate-specific antigen (PSA) response and overall survival (OS).
A total of 40 patients were included of which seventeen had a tumour with a pathogenic DDR aberration (DDR+), of which eight had defects in BRCA1/2. DDR+ patients had an equal varying response to PSMA-RLT compared to those without pathological DDR anomalies (DDR-) in terms of PFS (5.9 vs. 6.4 months, respectively; HR 1.14; 95% CI 0.58-2.25; p = 0.71), ≥50% PSA response (59% vs. 65%, respectively; p = 0.75) or OS (11.1 vs. 10.7 months, respectively; HR 1.40; 95% CI: 0.68-2.91; p = 0.36).
In this study of a selected cohort, pathogenic DDR aberrations were not associated with exceptional responsiveness to PSMA-RLT. Translational studies in larger prospective cohorts are warranted to associate DDR gene defects with differential responses to PSMA-RLT.
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Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Prospective validation of
Ga prostate specific membrane antigen positron emission tomography/computerized tomography is lacking in initial staging of prostate cancer. In this study we evaluated the ...diagnostic accuracy of
Ga prostate specific membrane antigen positron emission tomography/computerized tomography for detecting lymph node metastasis in patients with intermediate-high risk prostate cancer.
Patients with newly diagnosed prostate cancer and negative bone scan findings at greater than 10% MSKCC (Memorial Sloan Kettering Cancer Center) risk for lymph node metastasis were prospectively included in study from October 2017 to October 2018. In candidates for extended pelvic lymph node dissection
Ga prostate specific membrane antigen positron emission tomography/computerized tomography was performed prior to planned surgery. Scan results were evaluated in a second tumor board meeting to assess a potential change of management. Sensitivity, specificity, and positive and negative predictive value for detecting lymph node metastasis were calculated per patient and per resection template using histopathology as the reference. A positron emission tomography based change of management was also reported.
A total of 103 patients were eligible for analysis and 97 extended pelvic lymph node dissections were performed. In 41 patients (42.3%) there was a total of 85 lymph node metastases. Positron emission tomography was positive in 17 patients, resulting in 41.5% patient based sensitivity (95% CI 26.7-57.8) for detecting lymph node metastasis. The patient based specificity rate was 90.9% (95% CI 79.3-96.6), and positive and negative predictive values were 77.3% (95% CI 54.2-91.3) and 67.6% (95% CI 55.6-77.7), respectively. A positron emission tomography based change of treatment was observed in 13 patients (12.6%).
In patients with newly diagnosed prostate cancer at greater than 10% MSKCC risk for lymph node involvement
Ga prostate specific membrane antigen positron emission tomography/computerized tomography detected lymph node metastasis with high specificity and moderate sensitivity. This led to a treatment change in 12.6% of patients.
Background
External cooling of the salivary glands is advised to prevent xerostomia in lutetium-177-PSMA treatment for advanced prostate cancer. Since evidence addressing this subject is sparse, this ...study aims to determine impact of icepacks application on uptake in salivary glands. Eighty-nine patients referred for gallium-68-PSMA PET/CT for (re)staging of prostate cancer were prospectively included. Twenty-four patients were scanned with unilateral (solely left-sided) icepacks; 20 with bilateral icepacks; 45 without icepacks. Icepacks were applied approximately 30 minutes prior to tracer injection. PET/CT acquisition started 1 hour postinjection. Radiotracer uptake was measured in the parotid- and submandibular glands.
Results
When comparing the intervention group with the control group, uptake in the left parotid gland significantly differed: SUV
max
: 11.07 ± 3.53 versus 12.95 ± 4.16;
p
= 0.02. SUV
peak
: 9.91 ± 3.14 versus 11.45 ± 3.61;
p
= 0.04. SUV
max
and SUV
peak
were reduced with 14.52% and 13.45%. All other SUV values did not significantly differ. Patients with bilateral icepacks showed no significant differences in PSMA uptake compared to the control group (all:
p
> 0.05). Intra-patient analysis revealed some significant differences in SUV
max
and SUV
peak
between the cooled and non-cooled parotid gland (SUV
max
: 11.12 ± 3.71 versus 12.69 ± 3.75;
p
= 0.00. SUV
peak
: 9.93 ± 3.32 versus 11.25 ± 3.25;
p
= 0.00).
Conclusions
Impact of icepacks on PSMA uptake seems to be limited to the parotid glands. As clinical relevance of these findings is debatable, structural application of icepacks in the setting of lutetium-177 PSMA therapy needs careful consideration.
Prostate specific membrane antigen (PSMA) directed radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. However, it is still poorly ...understood why approximately 40% of the patients does not respond to PSMA-RLT. The aims of this study were to evaluate the pretreatment PSMA expression on immunohistochemistry (IHC) and PSMA uptake on PET/CT imaging in mCRPC patients who underwent PSMA-RLT. We correlated these parameters and a cell proliferation marker (Ki67) to the therapeutic efficacy of PSMA-RLT.
In this retrospective study, mCRPC patients who underwent PSMA-RLT were analyzed. Patients biopsies were scored for immunohistochemical Ki67 expression, PSMA staining intensity and percentage of cells with PSMA expression. Moreover, the PSMA tracer uptake of the tumor lesion(s) and healthy organs on PET/CT imaging was assessed. The primary outcome was to evaluate the association between histological PSMA protein expression of tumor in pre-PSMA-RLT biopsies and the PSMA uptake on PSMA PET/CT imaging of the biopsied lesion. Secondary outcomes were to assess the relationship between PSMA expression and Ki67 on IHC and the progression free survival (PFS) and overall survival (OS) following PSMA-RLT.
In total, 22 mCRPC patients were included in this study. Nineteen (86%) patients showed a high and homogenous PSMA expression of >80% on IHC. Three (14%) patients had low PSMA expression on IHC. Although there was limited PSMA uptake on PET/CT imaging, these 3 patients had lower PSMA uptake on PET/CT imaging compared to the patients with high PSMA expression on IHC. Yet, no correlation was found between PSMA uptake on PET/CT imaging and PSMA expression on IHC (SUVmax: R2 = 0.046 and SUVavg: R2 = 0.036). The 3 patients had a shorter PFS compared to the patients with high PSMA expression on IHC (HR: 4.76, 95% CI: 1.14-19.99; P = .033). Patients with low Ki67 expression had a longer PFS and OS compared to patients with a high Ki67 expression (HR: 0.40, 95% CI: 0.15-1.06; P = .013)
The PSMA uptake on PSMA-PET/CT generally followed the PSMA expression on IHC. However, heterogeneity may be missed on PSMA-PET/CT. Immunohistochemical PSMA and Ki67 expression in fresh tumor biopsies, may contribute to predict treatment efficacy of PSMA-RLT in mCRPC patients. This needs to be further explored in prospective cohorts.
In this retrospective observational study we focused on the failure of prostate specific membrane antigen-radioligand therapy. Therefore we evaluated the correlation between PSMA uptake on positron emission tomography/computed tomography and PSMA protein expression on IHC on fresh biopsy leasion of mCRPC-patients. Secondly we PSMA uptake on PET/CT, protein expression of PSMA and Ki67 were associated with the therapeutic outcome of PSMA-RLT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Imaging with radiotracers targeting the prostate-specific membrane antigen (PSMA) receptor is identified as a promising novel technique in prostate cancer (PCa) detection. In this paper we aim to ...summarize the current knowledge derived from the literature as well as the authors’ experiences on PSMA PET/CT in initial staging of PCa. PSMA PET/CT lesion- and template-based sensitivity and specificity respectively ranged from 35.1–96.1% and 96–100%. Patient-based sensitivity and specificity respectively ranged from 33.3–100% and 95–100%. Accuracy was 92% (95% CI 88–95) versus 65% (95% CI 60–69) compared to conventional imaging (CT and skeletal scintigraphy). PSMA PET/CT is superior for detection of metastases in primary PCa compared to conventional imaging. Also, PSMA PET/CT has a high specificity and moderate sensitivity for lymph node detection in primary PCa. For adequate initial staging, extended pelvic lymph node dissection (ePLND) will still be required, however, PSMA PET/CT can induce important management changes.
The production of endogenous adenosine during secretagogue stimulation of CFTR leads to feedback inhibition limiting further chloride secretion in the rectal gland of the dogfish shark (Squalus ...acanthias). In the present study, we examined the role of AMP-kinase (AMPK) as an energy sensor also modulating chloride secretion through CFTR. We found that glands perfused with forskolin and isobutylmethylxanthine (F + I), potent stimulators of chloride secretion in this ancient model, caused significant phosphorylation of the catalytic subunit Thr
of AMPK. These findings indicate that AMPK is activated during energy-requiring stimulated chloride secretion. In molecular studies, we confirmed that the activating Thr
site is indeed present in the α-catalytic subunit of AMPK in this ancient gland, which reveals striking homology to AMPKα subunits sequenced in other vertebrates. When perfused rectal glands stimulated with F + I were subjected to severe hypoxic stress or perfused with pharmacologic inhibitors of metabolism (FCCP or oligomycin), phosphorylation of AMPK Thr
was further increased and chloride secretion was dramatically diminished. The pharmacologic activation of AMPK with AICAR-inhibited chloride secretion, as measured by short-circuit current, when applied to the apical side of shark rectal gland monolayers in primary culture. These results indicate that that activated AMPK, similar to adenosine, transmits an inhibitory signal from metabolism, that limits chloride secretion in the shark rectal gland.
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