Can 68 Ga-PSMA positron emission tomography and multiparametric MRI guide treatment for biochemical recurrence after radical prostatectomy?

OBJECTIVE: To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) and Gallium-68 (68 Ga)-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in guiding salvage therapy for patients with biochemical recurrence (BCR) post-radical prostatectomy. PATIENTS AND METHODS: Patients were evaluated with paired mpMRI and 68 Ga-PSMA PET/CT scans for BCR (prostate-specific antigen [PSA] >0.2 ng/mL). Patient, tumour, PSA and imaging characteristics were analysed with descriptive statistics. RESULTS: A total of 117 patients underwent paired scans to investigate BCR, of whom 53.0% (62/117) had detectable lesions on initial scans and 47.0% (55/117) did not. Of those without detectable lesions, 8/55 patients proceeded to immediate salvage radiotherapy (sRT) and 47/55 were observed. Of patients with negative imaging who were initially observed, 46.8% (22/47) did not reach threshold for repeat imaging, while 53.2% were rescanned due to rising PSA levels. Of these rescanned patients, 31.9% (15/47) were spared sRT due to proven distant disease, or due to absence of disease on repeat imaging. Of the original 117 patients, 53 (45.3%) were spared early sRT due to absence of disease on imaging or presence of distant disease, while those undergoing delayed sRT still maintained good PSA responses. Of note, patients with high-risk features who underwent sRT despite negative imaging demonstrated satisfactory PSA responses to sRT. Study limitations include the observational design and absence of cause-specific or overall survival data. CONCLUSION: Our findings support the use of mpMRI and 68 Ga-PSMA PET/CT in guiding timing and necessity of salvage therapy tailored to detected lesions, with potential to reduce unnecessary sRT-related morbidity. Larger or randomized trials are warranted to validate this.

Distant Nodes Seen on PSMA PET-CT Staging Predicts Post-Treatment Progression in Men with Newly Diagnosed Prostate Cancer-A Prospective Cohort Study.

PSMA PET-CT scans are now recommended in international urological guidelines for primary staging and re-staging of prostate cancer. However, there is little published literature on the clinical outcomes for patients after treatment decisions made using PSMA PET-CT results. This is a multisite, prospective cohort study investigating the clinical outcomes of men who received treatment plans based on PSMA PET-CT results for primary staging. Men with biopsy proven prostate cancer received a PSMA PET-CT scan for primary staging. Treatment plans were recommended by multidisciplinary teams (MDT). After treatment, these men were followed with 6 monthly PSA tests and imaging or biopsies if recommended by MDT. The primary outcome was treatment progression defined as the addition or change of any treatment modalities such as androgen deprivation therapy, radiation therapy or chemotherapy. In total, 80% of men did not have any treatment progression after enactment of treatment based on PSMA PET-CT primary staging results at 29 months of follow up. Men who had distant nodes seen on PSMA PET-CT had a 5 times increased risk of treatment progression. Larger studies with longer follow up are needed to validate our results and optimise the way clinicians use PSMA PET-CT results to guide management.

Defining Prostatic Vascular Pedicle Recurrence and the Anatomy of Local Recurrence of Prostate Cancer on Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography.

Background: The term local recurrence in prostate cancer is considered to mean persistent local disease in the prostatic bed, most commonly at the site of the vesicourethral anastomosis (VUA). Since the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging for assessment of early biochemical recurrence (BCR), we have found histologically confirmed prostate cancer in the prostatic vascular pedicle (PVP). If a significant proportion of local recurrences are distant to the VUA, it may be possible to alter adjuvant and salvage radiation fields in order to reduce the potential morbidity of radiation in selected patients. Objective: To describe PVP local recurrence and to map the anatomic pattern of prostate bed recurrence on PSMA PET/CT. Design setting and participants: This was a retrospective multicentre study of 185 patients imaged with PSMA PET/CT following radical prostatectomy (RP) between January 2016 and November 2018. All patient data and clinical outcomes were prospectively collected. Recurrences were documented according to anatomic location. For patients presenting with local recurrence, the precise location of the recurrence within the prostate bed was documented. Intervention: PSMA PET/CT for BCR following RP. Results and limitations: A total of 43 local recurrences in 41/185 patients (22%) were identified. Tumour recurrence at the PVP was found in 26 (63%), VUA in 15 (37%), and within a retained seminal vesicle and along the anterior rectal wall in the region of the neurovascular bundle in one (2.4%) each. Histological and surgical evidence of PVP recurrence was acquired in two patients. The study is limited by its retrospective nature with inherent selection bias. This is an observational study reporting on the anatomy of local recurrence and does not include follow-up for patient outcomes. Conclusions: Our study showed that prostate cancer can recur in the PVP and is distant to the VUA more commonly than previously thought. This may have implications for RP technique and for the treatment of selected patients in the local recurrence setting. Patient summary: We investigated more precise identification of the location of tumour recurrence after removal of the prostate for prostate cancer. We describe a new definition of local recurrence in an area called the prostatic vascular pedicle. This new concept may alter the treatment recommended for recurrent disease.

PSMA PET-CT Imaging Predicts Treatment Progression in Men with Biochemically Recurrent Prostate Cancer-A Prospective Study of Men with 3 Year Follow Up.

Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is a novel imaging modality used to stage recurrent prostate cancer. It has the potential to improve prognostication and ultimately guide the timing of treatment for men with recurrent prostate cancer. This study aims to assess the clinical impact of PSMA PET-CT by analyzing its predictive value of treatment progression after 3 years of follow-up. In this prospective cohort study of 100 men, patients received a PSMA PET-CT for restaging of their disease which was used by a multi-disciplinary team to make a treatment decision. The primary endpoint was treatment progression. This was defined as the addition or change of any treatment modalities such as androgen deprivation therapy (ADT), radiation therapy or chemotherapy. The median follow-up time was 36 months (IQR 24-40 months). No treatment progression was found in 72 (75%) men and therefore 24 (25%) patients were found to have treatment progression. In men with a negative PSMA PET-CT result, 5/33 (15.1%) had treatment progression and 28/33 (84.8%) had no treatment progression. In conclusion, clinical decisions made with PSMA PET-CT results led to 75% of men having no treatment progression at 3 years of follow-up. In men with negative PSMA PET-CT results, this increased to 85% of men.

Combined Utility of 68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Multiparametric Magnetic Resonance Imaging in Predicting Prostate Biopsy Pathology.

BACKGROUND: 68Gallium-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-11 PET) is a valuable staging tool, but its utility in characterising primary prostate cancer remains unclear. The maximum standardised uptake value (SUVmax) is a quantification measure of highest radiotracer uptake within PET-avid lesions. OBJECTIVE: To assess the utility of SUVmax in detecting clinically significant prostate cancer (csPCa) on biopsy alone and in combination with multiparametric magnetic resonance imaging (mpMRI). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of 200 men who underwent 68Ga-PSMA-11 PET/CT, mpMRI, and transperineal template prostate biopsy between 2016 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary outcomes were detection of grade group (GG) 3-5 and GG 2-5 prostate cancer, respectively. We used the Mann-Whitney U test to compare SUVmax by GG, and calculated sensitivity and specificity for csPCa detection via 68Ga-PSMA-11 PET/CT, mpMRI, and both. Multivariable logistic regression analyses were used to identify predictors of csPCa on biopsy. RESULTS AND LIMITATIONS: The median SUVmax was greater for GG 3-5 tumours (6.40, interquartile range [IQR] 4.47-11.0) than for benign and GG 1-2 tumours (3.14, IQR 2.55-3.91; p < 0.001). The median SUVmax was greater for GG 3 (5.70, IQR 3.68-8.67) than for GG 2 (3.47, IQR 2.70-4.74; p < 0.001). For GG 3-5 disease, sensitivity was 86.5%, 95.9%, and 98.6%, and the negative predictive value (NPV) was 88.4%, 88.5%, and 93.3% using SUVmax ≥4, a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3-5, and both, respectively. This combined model detected more GG 3-5 disease than mpMRI alone (98.6% vs 95.9%; p = 0.04). SUVmax was an independent predictor of csPCa for GG 3-5 disease only (odds ratio 1.27 per unit, 95% confidence interval 1.13-1.45). Our results are limited by the retrospective study design. CONCLUSIONS: Greater SUVmax on 68Ga-PSMA-11 PET/CT is associated with detection of GG 3-5 cancer on biopsy. The combination of PI-RADS score and SUVmax provides higher sensitivity and NPV than either alone. 68Ga-PSMA-11 PET/CT may be useful alongside mpMRI in improving risk stratification for localised disease. PATIENT SUMMARY: The amount of a radioactive tracer taken up in the prostate during a type of scan called PET (positron emission tomography) can predict whether aggressive prostate cancer is likely to be found on biopsy. This may complement the more usual type of scan, MRI (magnetic resonance imaging), used to detect prostate cancer.

68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography Maximum Standardized Uptake Value as a Predictor of Gleason Pattern 4 and Pathological Upgrading in Intermediate-Risk Prostate Cancer.

PURPOSE: Accurate risk stratification remains a barrier for the safety of active surveillance in patients with intermediate-risk prostate cancer. [68Ga]Ga-PSMA-11 prostate-specific membrane antigen positron emission tomography/computerized tomography (68Ga-PSMA PET/CT) and the maximum standardized uptake value (SUVmax) may improve risk stratification within this population. MATERIALS AND METHODS: We reviewed men with International Society for Urological Pathology Grade Group (GG) 2-3 disease on transperineal template biopsy undergoing 68Ga-PSMA PET/CT from November 2015 to January 2021. Primary outcome was the presence of high percentage Gleason pattern 4 (GP4) disease per segment at surgery at 3 thresholds: >/<50% GP4, >/<20% GP4, and >/<10% GP4. SUVmax was compared by GP4, and multivariable logistic regression examined the relationship between SUVmax and GP4. Secondary outcome was association between SUVmax and pathological upgrading (GG 1/2 to GG ≥3 from biopsy to surgery). RESULTS: Of 220 men who underwent biopsy, 135 men underwent surgery. SUVmax was higher in high GP4 groups: 5.51 (IQR 4.19-8.49) vs 3.31 (2.64-4.41) >/<50% GP4 (p <0.001); 4.77 (3.31-7.00) vs 3.13 (2.64-4.41) >/<20% GP4 (p <0.001); and 4.54 (6.10-3.13) vs 3.03 (2.45-3.70) >/<10% GP4 (p <0.001). SUVmax remained an independent predictor of >50% (OR=1.39 [95%CI 1.18-1.65], p <0.001) and >20% (OR=1.24 [1.04-1.47], p=0.015) GP4 disease per-segment, and of pathological upgrading (OR=1.22 [1.01-1.48], p=0.036). SUVmax threshold 4.5 predicted >20% GP4 with 58% specificity, 85% sensitivity, positive predictive value 75% and negative predictive value 72%. Threshold 5.4 predicted pathological upgrading with 91% specificity and negative predictive value 94%. CONCLUSIONS: SUVmax on 68Ga-PSMA PET/CT is associated with GP4. SUVmax may improve risk stratification for men with intermediate-risk prostate cancer.

Detection and localisation of primary prostate cancer using 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography compared with multiparametric magnetic resonance imaging and radical prostatectomy specimen pathology.

OBJECTIVE: To compare the accuracy of 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. PATIENTS AND METHODS: Retrospective review of men who underwent 68 Ga-PSMA PET/CT and mpMRI for primary prostate cancer before RP across four centres between 2015 and 2018. Patients undergoing imaging for recurrent disease or before non-surgical treatment were excluded. We defined pathological index tumour as the lesion with highest International Society of Urological Pathology Grade Group (GG) on RP specimen pathology. Our primary outcomes were rates of accurate detection and localisation of RP specimen pathology index tumour using 68 Ga-PSMA PET/CT or mpMRI. We defined tumour detection as imaging lesion corresponding with RP specimen tumour on any imaging plane, and localisation as imaging lesion matching RP specimen index tumour in all sagittal, axial, and coronal planes. Secondary outcomes included localisation of clinically significant and transition zone (TZ) index tumours. We defined clinically significant disease as GG 3-5. We used descriptive statistics and the Mann-Whitney U-test to define and compare demographic and pathological characteristics between detected, missed and localised tumours using either imaging modality. We used the McNemar test to compare detection and localisation rates using 68 Ga-PSMA PET/CT and mpMRI. RESULTS: In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68 Ga-PSMA PET/CT and mpMRI in the detection of any tumour (94% vs 95%, P > 0.9). There was also no significant difference between localisation of all index tumours (91% vs 89%, P = 0.47), clinically significant index tumours (96% vs 91%, P = 0.15) or TZ tumours (85% vs 80%, P > 0.9) using 68 Ga-PSMA PET/CT and mpMRI. Limitations include retrospective study design and non-central review of imaging and pathology. CONCLUSION: We found no significant difference in the detection or localisation of primary prostate cancer between 68 Ga-PSMA PET/CT and mpMRI. Further prospective studies are required to evaluate a combined PET/MRI model in minimising tumours missed by either modality.

Ga-labeled Prostate-specific Membrane Antigen Ligand-positron-emission Tomography: Still Just the Tip of the Iceberg.

OBJECTIVES: To assess the performance of Ga-labeled prostate-specific membrane antigen ligand-positron-emission tomography (Ga-PSMA PET) for positive lymph nodes on imaging after curatively intended radical prostatectomy. PATIENTS AND METHODS: Seventeen patients with biochemical recurrence after radical prostatectomy undergoing robot-assisted salvage lymphadenectomy for positive lymph nodes on imaging were included in this single surgeon study. The performance of Ga-PSMA PET was assessed on per patient, per lesion, per landing site and per laterality level using sensitivity, specificity, and negative and positive predictive value analysis. RESULTS: A total of 34 positive nodes were detected on Ga-PSMA PET with a median of 2 nodes per patient (IQR 1-3 nodes per patient). Sixty six nodes were pathologically disease positive from 14 patients, with a median of 2 positive nodes per patient (IQR 1-6). Three patients had no pathologically detectable disease. On a per patient basis, the positive predictive value was 82%. Sensitivity, specificity, and negative predictive value were not able to be calculated as all patients had disease recurrence with a detectable prostate-specific antigen.On a "per lesion" basis, the sensitivity, specificity, positive predictive value, and negative predictive value were 36.7%, 96.9%, 73.5%, and 86.7%, respectively. CONCLUSION: Our study indicates that sensitivity of Ga-PSMA PET in the salvage setting is not yet sufficient to detect all sites of metastasis. Therefore, imaging-guided metastasis targeted treatment is likely to fail given the likely concomitant imaging negative more widespread disease.

Bone scans are reliable for the identification of lumbar disk and facet pathology.

Study Design Surgeon survey. Objective To evaluate the reliability of bone single-photon emission computed tomography (SPECT) versus bone SPECT images co-registered with computed tomography (bone SPECT-CT) by analyzing interobserver agreement for identification of the anatomical location of technetium(99m)-labeled oxidronate uptake in the lumbar disk and/or facet joint. Methods Seven spine surgeons interpreted 20 bone scans: 10 conventional black-and-white tomograms (bone SPECT) and 10 color-graded bone SPECT-CT scans. Each surgeon was asked to identify the location of any diagnostically relevant uptake in the disk and/or facet joint between L1 and S1. Reliability was evaluated using the free-marginal kappa statistic, and the level of agreement was assessed using the Landis and Koch interpretation. Results Conventional bone SPECT scans and bone SPECT-CT scans were reliable for the identification of diagnostically relevant uptake, with bone SPECT-CT having higher reliability (kappa = 0.72) than bone SPECT alone (0.59). Bone SPECT and bone SPECT-CT were also reliable in identifying disk pathology, with kappa values of 0.72 and 0.81, respectively. However, bone SPECT-CT was more reliable (0.81) than bone SPECT (0.60) when identifying facet disease. Conclusions For the identification of disk pathology, it is reasonable to use either conventional bone SPECT or bone SPECT-CT; however, bone SPECT-CT is more reliable for facet joint pathology.

Indirect foraminal decompression is independent of metabolically active facet arthropathy in extreme lateral interbody fusion.

STUDY DESIGN: Retrospective analysis of prospectively collected, nonrandomized radiographical data. OBJECTIVE: To examine the relationship between the presence of preoperative metabolically active facet arthropathy (FA) and the amount of indirect foraminal decompression gained after extreme lateral interbody fusion (XLIF). SUMMARY OF BACKGROUND DATA: Although evidence of significant radiographical indirect decompression after XLIF has been shown, the relationship between the extent of indirect decompression and the presence of potentially attenuating, FA is yet to be studied. METHODS: A prospective database of consecutive patients undergoing XLIF was retrospectively analyzed. Posterior disc height, foraminal height, and cross-sectional foraminal area were measured on computed tomographic scans obtained preoperatively and 2 days postoperatively. The selected radiographical parameters were examined with respect to the presence of FA based on preoperative computed tomographic and bone scans. RESULTS: Fifty-two consecutive patients underwent 79 levels of XLIF without direct decompression. Average age was 66.4 years and 34 (65.4%) were females. Surgery resulted in significant increases in posterior disc height 3.0 to 5.7 mm (89.0% increase), P<0.0001; foraminal height 1.4 to 1.7 cm (38.0% increase), P<0.0001; and foraminal area 1.1 to 1.4 cm (45.1% increase), P<0.0001. These increases were independent of the presence of metabolically active arthropathy. CONCLUSION: Significant indirect neural decompression is possible in XLIF, regardless of the presence of metabolically active FA. LEVEL OF EVIDENCE: 3.

Co-registration of isotope bone scan with CT scan and MRI in the investigation of spinal pathology.

Image fusion software enables technetium(99m)-methylene diphosphonate (Tc(99m)-MDP) bone scan images to be co-registered with CT scan or MRI, allowing greater anatomical discrimination. We examined the role of bone scan images co-registered with CT scan or MRI in the investigation of patients presenting with axial spinal pain and/or limb pain. One hundred and thirty-nine consecutive patients were examined, and thereafter investigated with CT scan, MRI, and/or dynamic plain films. At this point diagnosis (pathology type and anatomical site) and treatment intention were declared. The co-registered Tc(99m)-MDP bone scan images were then studied, after which diagnosis (pathology type and anatomical site) and treatment intention were re-declared. This data were then analysed to determine whether the addition of co-registered bone scan images resulted in any change in diagnosis or treatment intention. The most significant change in diagnosis was pathology type (10%). Anatomical site changed markedly without overlap of the pre and post-isotope fields in 5%, and with overlap in 10%. Treatment intention had a major change in 3.6% and minor change in 8.6%. In the two groups where there was (i) no obvious pathology after full pre-isotope investigation, or (ii) a spinal fusion under suspicion, addition of the bone scan information led to a major change in the pathology and/or anatomical localisation in 18% and 19%, respectively. The addition of co-registered Tc(99m)-MDP bone scan images offers significant diagnostic assistance, particularly in the difficult diagnostic groups where a failed spinal fusion may be the suspected pain generator, or when no pain generator can otherwise be found.

Vascularity of the femoral head after Birmingham hip resurfacing. A technetium Tc 99m bone scan/single photon emission computed tomography study.

To investigate the vascularity of femoral heads after Birmingham hip resurfacing (BHR), we used a visual scale to assess technetium Tc 99m HDP planar and single photon emission computed tomography bone scans of 36 arthroplasties in 32 asymptomatic patients for an average of 26 months after BHR. The validity of this method was demonstrated by comparing levels of radiation detected from within and immediately adjacent to a BHR prosthesis placed on a technetium Tc 99m radioisotope tracer-filled hollow tube and further validated in vivo by comparing radiation levels from bilateral hip scans in human subjects with 2 normal hips and with unilateral BHR. All femoral heads scanned postoperatively appeared vascular. We speculate that preserved femoral head vascularity after BHR may be related to increased intraosseous blood supply from metaphyseal vessels in arthritic hips.

Nuclear cardiology.

Nuclear cardiology has shown double digit growth yearly over the last few years and remains the second most commonly performed noninvasive cardiac imaging investigation of choice. Approximately 9 million studies performed yearly in the U.S. alone. As cardiovascular disease remains the largest healthcare problem around the world despite increasing healthcare spending there is growing interest to enhance the use of cost effective diagnostic tools, such as nuclear cardiology. Recent development of technology has seen the addition of hybrid imaging tools such PET/CT and SPECT/CT into the armorial. More data is expected to become available on this subject within the next few years, and we also expect several molecular imaging tests to become available for clinical use. Despite easy availability of these diagnostic tools, cardiac mortality and morbidity in patients with long term diabetes and also in the postoperative setting remains unexpectedly high and emergency department physician are still being sued after patients being discharged with undiagnosed chest pain. The value of the use of nuclear cardiology studies is briefly reviewed in these clinical settings.