Treatment response assessment in mCRPC: is PSMA-PET/CT going to take the lead?

The assessment of response to therapy in prostate cancer (PCa) patients is an ongoing, open issue. Prostate-specific antigen has limitations, especially in advanced metastatic PCa, which often displays intratumor variability in terms of response to therapy. Conventional imaging (i.e. computerized tomography and bone scan) is of limited use for its low sensitivity and specificity. Positron-emission tomography (PET) with prostate-specific membrane antigen (PSMA) demonstrated higher sensitivity and specificity, and novel PSMA-based criteria have been recently proposed for treatment response, with promising results in different scenarios, from chemotherapy to radioligand therapy. PSMA-based criteria have been found to outperform the current RECIST 1.1 and Prostate Cancer Working Group 3 frameworks in describing the behavior of PCa, precisely assessing tumor phenotypes through molecular-imaging-derived parameters. This review critically explores the current evidence about the role of PSMA PET/computed tomography in the assessment of treatment response.

PSMA PET/CT patterns of recurrence after mono-brachytherapy in men with low and intermediate prostate cancer and subsequent management.

PURPOSE: Brachytherapy as monotherapy is a recommended treatment option for men with low to intermediate risk prostate cancer. Local recurrence is difficult to identify. This study investigated PSMA PET/CT for recurrence after brachytherapy, as well as their subsequent management when recurrence occurred only within the prostate. METHODS: We performed a retrospective single-center analysis for patients who were treated with brachytherapy as monotherapy for prostate cancer from May 2002 to May 2021 and who underwent a PSMA PET/CT for BCR. We report the findings on PSMA PET/CT, quantitative parameters, as well as the later management of the patients. RESULTS: Forty patients were identified, who underwent PSMA PET/CT to investigate a rising PSA at a median (IQR) of 7 years (3.0-10.8) after initial therapy. Median (IQR) PSA at time of PSMA PET/CT was 6.54 ng/mL (3.9-15.5). On PSMA PET/CT, 20/40 (50%) men had prostate-only recurrence. Of the 20 patients with prostate-only recurrence, 8/20 (40%) had recurrence in a high-dose radiation zone, versus 7/20 (35%) in an under-covered zone. On PSMA PET/CT, recurrence within the prostate had median (IQR) SUVmax 10.4 (5.1-15.7) and volume 2.9 mL (2.0-11.2). Subsequent management of these patients with local recurrence included surveillance followed by ADT (9/20, 45%). For those with surveillance followed by ADT, the mean time before introduction of ADT was 4.1 years (range 1-8 years).

Evaluating response to radium-223 using 68Ga-PSMA PET/CT imaging in patients with metastatic castration-resistant prostate cancer.

AIM: Conventional imaging techniques and prostate-specific antigen (PSA) values are not useful to follow-up patients during Radium-223 treatment. The study aimed to evaluate the predictive value of prostate-specific membrane antigen PSMA PET/CT-based response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Radium-223 dichloride treatment. MATERIALS AND METHODS: Patients treated with radium-223, having performed two 68Ga-PSMA-11 PET/CT scans (baseline 1 month before treatment initiation and follow-up 2 weeks after the third cycle), were retrospectively evaluated. Visual and quantitative PET image analyses were performed, and patients were dichotomized into progressive (PD) and non-PD according to Response Evaluation Criteria in PSMA­imaging (RECIP1.0) and PSMA-PET Progression criteria (PPP). The primary endpoint was overall survival (OS). Cohen's Kappa (κ) was used to test the agreement between the two criteria. The Cox regression hazard model and Kaplan-Meier method were used for survival analyses. RESULTS: Twenty-eight mCRPC patients were evaluated. Sixteen (43%) and 18 (64%) patients had PD according to RECIP1.0 and PPP, respectively; κ = 0.85 (95% CI 0.65-1.00). After a median follow-up of 16 months (interquartile IQR 9-33), 20 (71%) patients died. Patients with PSMA PD showed a higher risk of death than non-PD according to RECIP1.0 (HR = 2.9; 95% CI 1.14-7.46; p = 0.029) and PPP (HR = 2.8; 95% CI 1.04-7.64; p = 0.042). For both criteria, the median OS was shorter for PD than non-PD (37 vs. 12 months, Log-rank; p < 0.05). The C-index for RECIP1.0 and PPP were almost equal (0.66 and 0.63; respectively). CONCLUSION: This study demonstrated that PSMA-PET/CT imaging is valuable for monitoring radium-223 treatment. Both PSMA PET/CT response criteria (RECIP1.0 and PPP) perform similarly predicting OS at follow-up after three cycles of radium-223. These findings urge further validation in prospective trials.

Unusual Prostate-Specific Membrane Antigen (PSMA) Splenic Uptake in a Patient With Prostate Cancer.

There are many benefits to early detection of prostate cancer, including improved survival rates, less invasive treatment options, and better quality of life. Apart from traditional tests and imaging (including the prostate-specific antigen (PSA) test, digital rectal exam, biopsy, computed tomography (CT), and magnetic resonance imaging (MRI)), an imaging technique called prostate-specific membrane antigen positron emission tomography (PSMA PET) is more specific and sensitive, targeting PSMA expressed by prostate cancer cells on their surface. This case report describes a 62-year-old male with metastatic prostate adenocarcinoma and unusual PSMA uptake in the spleen. Elevated PSA levels and MRI indicated aggressive prostate cancer, confirmed by a Gleason score of 7 from biopsies. A PSMA PET/CT scan showed intense activity in both the prostate and spleen, initially suggesting metastasis. However, further imaging identified the splenic lesion as a benign hemangioma. This case showcases the importance of thorough diagnostic evaluations for distinguishing metastatic disease from benign conditions to ensure accurate diagnosis and appropriate treatment.

Exophthalmos as the initial presentation of metastatic prostate cancer.

Primary metastatic prostate cancer to the orbit is exceedingly rare. Benign lesions, including meningioma, have demonstrated PSMA expression and can be visualized using PSMA-based PET tracers. We report the findings of 18F-PSMA-1007 PET/CT in a 76-year-old man with progressive confusion and long-standing blindness of the left eye. PET/CT scan revealed increased uptake of PSMA in the orbital and temporal region, and other sites throughout the body. Histopathological examination after biopsy of the left orbit showed adenocarcinoma of the prostate. This case substantiates the diverse clinical and radiological presentations of metastatic prostate cancer and underscores the diagnostic significance of targeted biopsy.

Prognostic value of PSMA PET in predicting long-term biochemical control following curative intent treatment for prostate cancer.

INTRODUCTION: The aim of this study is to investigate the prognostic value of 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) metrics in predicting long-term biochemical failure-free survival (BFFS) following curative intent treatment for prostate cancer. METHODS: We completed a prospective study that followed men who had PSMA PET for staging of newly diagnosed prostate cancer between 2015 and 2017 who went on to have curative intent treatment with radiotherapy (RT) or radical prostatectomy (RP). PSMA PET CT imaging was reported and the intraprostatic maximum standardised uptake value (SUVmax) was recorded. The primary outcome was BFFS. Statistical analysis included descriptive statistics, Cox proportional hazards (PH) models, Kaplan-Meier survival analysis and a regression tree structured method. RESULTS: A total of 183 men were included in the analysis with a median age of 66 years and the majority of patients (55.2%) had ISUP grade 1-3 disease. All patients had PSMA PET staging prior to curative intent treatment with RP (66.1%) or external beam radiotherapy (33.9%). PSMA-avid pelvic nodes were present in 26 patients but were not associated with worse biochemical control. A PSMA SUVmax of the prostate primary greater than the median (>5.6) was associated with a lower BFFS (HR: 4.4, 95% CI 1.42-3.72, P = 0.01). A multivariate Cox model incorporating initial biopsy grade, age and PSMA SUVmax showed that PSMA SUVmax was an independent predictor of BFFS. The RT-structured method identified an optimal threshold of 6.8 for PSMA SUVmax, above which patients with ISUP 1-3 disease had a significantly worse BFFS. CONCLUSION: PSMA SUVmax is a strong predictor of BFFS in patients with non-metastatic prostate cancer who underwent curative intent treatment. Patients with low-risk disease on biopsy (ISUP 1-3) but high PSMA SUVmax may have biochemical failure risk analogous to higher-risk disease (ISUP 4-5). These findings allow for further risk stratification and prognosis of patients with newly diagnosed prostate cancer planned for definitive treatment.

Comparative Performance of 68Ga-PSMA-11 PET/CT and Conventional Imaging in the Primary Staging of High-Risk Prostate Cancer Patients Who Are Candidates for Radical Prostatectomy.

This prospective study aimed to (1) compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with respect to conventional imaging (computed tomography (CT) and bone scintigraphy (BS)) in the primary staging of high-risk prostate cancer (PCa) patients and (2) validate PSMA-PET/CT accuracy in pelvic nodal staging in comparison with postoperative histopathology and assess PSMA-PET/CT's impact on patient management. Sixty castration-sensitive high-risk (ISUP 4-5 and/or PSA > 20 ng/mL and/or cT3) PCa patients eligible for radical prostatectomy were enrolled (median PSA 10.10 [IQR: 6.22-17.95] ng/mL). PSMA-PET/CT, compared with CT, identified nodal (N) and/or distant metastases (M1) in 56.7% (34/60) vs. 13.3% (8/60) (p < 0.001) of patients: N + 45% vs. 13.3% (p < 0.001), M1a 11.7% vs. 1.7% (p = 0.03), M1b 23.3% vs. 1.7% (p < 0.001). Compared with BS, PSMA-PET/CT localized unknown skeletal metastases in 15% (9/60) of cases, with no false negative findings. Overall, PSMA-PET/CT led to a TNM upstaging in 45.0% (27/60) of cases, with no evidence of downstaging, resulting in a change in management in up to 28.8% (17/59) of patients. Compared with histopathology data (n = 32 patients), the per-patient accuracy of PSMA-PET/TC for detecting pelvic nodal metastases was 90.6%. Overall, the above evidence supports the use of PSMA-PET/CT in the diagnostic workup of high-risk prostate cancer staging.

Volumetric Modulated Arc Therapy for High-Risk and Very High-Risk Locoregional Prostate Cancer in the Modern Era: Real-World Experience from an Asian Cohort.

This study retrospectively evaluates the clinical outcomes of definitive volumetric modulated arc therapy (VMAT) for high-risk or very high-risk locoregional prostate cancer patients from an Asian institution. Consecutive patients who received VMAT (76 Gy in 38 fractions) between January 2017 and June 2022 were included. Whole pelvic radiotherapy (WPRT) (46 Gy in 23 fractions) was employed for clinically node-negative disease (cN0) and a Roach estimated risk of ≥15%, as well as simultaneous integrated boost (SIB) of 55-57.5 Gy to node-positive (cN1) disease. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints included radiographic relapse-free survival (RRFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCSS). A total of 209 patients were identified. After a median follow-up of 47.5 months, the 4-year actuarial BRFS, RRFS, MFS and PCSS were 85.2%, 96.8%, 96.8% and 100%, respectively. The incidence of late grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 15.8% and 11.0%, respectively. No significant difference in cancer outcomes or toxicity was observed between WPRT and prostate-only radiotherapy for cN0 patients. SIB to the involved nodes did not result in increased toxicity. International Society of Urological Pathology (ISUP) group 5 and cN1 stage were associated with worse RRFS (p < 0.05). PSMA PET-CT compared to conventional imaging staging was associated with better BRFS in patients with ISUP grade group 5 (p = 0.039). Five-year local experience demonstrates excellent clinical outcomes. PSMA PET-CT staging for high-grade disease and tailored pelvic irradiation based on nodal risk should be considered to maximize clinical benefit.

[18F]AlF-PSMA-11 PET in diagnosing prostate cancer: a head-to-head comparison with [68Ga]Ga-PSMA-11 PET and an exploration of dual-phase scanning.

PURPOSE: To evaluate the physiological distribution and tumour detection ability of [18F]AlF-PSMA-11 positron emission tomography (PET) dual-phase scans in patients with prostate cancer (PCa). METHODS: As a retrospective study, clinical and PET data of PCa patients who underwent dual-phase [18F]AlF-PSMA-11 PET of routine scan (45-50 min) and delayed scan (120 min) from November 2020 to June 2021 were collected, and physiological and pathological regions of interest were quantified to determine the time-dependent maximum standardized uptake value (SUVmax) of [18F]AlF-PSMA-11. Part of the above subjects who underwent [68Ga]Ga-PSMA-11 PET in the following 6 months were included in a head-to-head comparison. The difference with a p-value < 0.05 was defined as statistical significance. Diagnosis accuracy of primary and metastatic lesions was measured referring to the surgical findings, pathology, and follow-up imaging. RESULTS: [68Ga]Ga-PSMA-11 and [18F]AlF-PSMA-11 were of the comparable uptake in glands in head, but the latter was of a significant lower distribution in liver and spleen. For the 25 patients initially diagnosed with prostate cancer and 3 patients with biochemical recurrence after radical surgery, the SUVmax of the primary lesions, lacrimal glands, parotid glands and submandibular glands was higher at 120 min compared to that at 45-50 min, but not a significant difference. SUVmax of the liver, spleen and bladder decreased significantly at 120 min, but the bladder SUVmax remained higher than that of primary lesions. SUVmax of the kidneys and centrum was the same in dual-phase scans. For the 31 primary lesions detected in [18F]AlF-PSMA-11 PET, both the SUVmax of the two phases kept the positive correlation with PSA, Gleason score and initial risk stratification. For the 39 distant metastatic lesions, 94.87% accuracy of routine scan and 100% accuracy of delayed scan were acquired, and 7.14% patients (2/28) benefited from the dual-phase [18F]AlF-PSMA-11 scans that revealed novel information on metastatic lesions compared to the routine scan. CONCLUSION: [18F]AlF-PSMA-11 PET expanded the time window and further decreased metabolic background of [68Ga]Ga-PSMA-11 PET. The dual-phase scan of [18F]AlF-PSMA-11 PET can benefit prostate cancer diagnosis via providing more PSMA-specific information.

PSMA PET improves characterization of dural-based intracranial lesions in patients with metastatic prostate cancer.

PURPOSE: Theranostic approaches combining prostate-specific membrane antigen (PSMA)-PET/CT or PET/MRI with PSMA-targeted radionuclide therapy have improved clinical outcomes in patients with prostate cancer (PCa) especially metastatic castrate resistant prostate cancer. Dural metastases in PCa are rare but can pose a diagnostic challenge, as meningiomas, a more common dural based lesions have been shown to express PSMA. The aim of this study is to compare PSMA PET parameters between brain lesions classified as dural metastases and meningiomas in prostate cancer patients. METHODS: A retrospective analysis of PSMA PET/CT scans in patients with PCa and intracranial lesions was conducted. Brain lesions were categorized as dural metastases or meningiomas based on MRI characteristics, longitudinal follow-up, and histopathological characteristics. Standardized uptake values (SUVmax) of each brain lesion were measured, along with SUV ratio referencing parotid gland (SUVR). SUVs between lesions classified as metastases and meningiomas, respectively, were compared using Mann-Whitney-test. Diagnostic accuracy was evaluated using ROC analysis. RESULTS: 26 male patients (median age: 76.5 years, range: 59-96 years) met inclusion criteria. A total of 44 lesions (7 meningiomas and 37 metastases) were analyzed. Median SUVmax and SUVR were significantly lower in meningiomas compared to metastases (SUVmax: 2.7 vs. 11.5, p = 0.001; SUVR: 0.26 vs. 1.05, p < 0.001). ROC analysis demonstrated AUC 0.903; the optimal cut-off value for SUVR was 0.81 with 81.1 % sensitivity and 100 % specificity. CONCLUSION: PSMA PET has the potential to differentiate meningiomas from dural-based metastases in patients with PCa, which can optimize clinical management and thus improve patient outcomes.

The impact of integrating PRIMARY score or SUVmax with MRI-based risk models for the detection of clinically significant prostate cancer.

PURPOSE: An MRI-based risk calculator (RC) has been recommended for diagnosing clinically significant prostate cancer (csPCa). PSMA PET/CT can detect lesions that are not visible on MRI, and the addition of PSMA PET/CT to MRI may improve diagnostic performance. The aim of this study was to incorporate the PRIMARY score or SUVmax derived from [68Ga]Ga-PSMA-11 PET/CT into the RC and compare these models with MRI-based RC to assess whether this can further reduce unnecessary biopsies. METHODS: A total of 683 consecutive biopsy-naïve men who underwent both [68Ga]Ga-PSMA-11 PET/CT and MRI before biopsy were temporally divided into a development cohort (n = 552) and a temporal validation cohort (n = 131). Three logistic regression RCs were developed and compared: MRI-RC, MRI-SUVmax-RC and MRI-PRIMARY-RC. Discrimination, calibration, and clinical utility were evaluated. The primary outcome was the clinical utility of the risk calculators for detecting csPCa and reducing the number of negative biopsies. RESULTS: The prevalence of csPCa was 47.5% (262/552) in the development cohort and 41.9% (55/131) in the temporal validation cohort. In the development cohort, the AUC of MRI-PRIMARY-RC was significantly higher than that of MRI-RC (0.924 vs. 0.868, p < 0.001) and MRI-SUVmax-RC (0.924 vs. 0.904, p = 0.002). In the temporal validation cohort, MRI-PRIMARY-RC also showed the best discriminative ability with an AUC of 0.921 (95% CI: 0.873-0.969). Bootstrapped calibration curves revealed that the model fit was acceptable. MRI-PRIMARY-RC exhibited near-perfect calibration within the range of 0-40%. DCA showed that MRI-PRIMARY-RC had the greatest net benefit for detecting csPCa compared with MRI-RC and MRI-SUVmax-RC at a risk threshold of 5-40% for csPCa in both the development and validation cohorts. CONCLUSION: The addition of the PRIMARY score to MRI-based multivariable model improved the accuracy of risk stratification prior to biopsy. Our novel MRI-PRIMARY prediction model is a promising approach for reducing unnecessary biopsies and improving the early detection of csPCa.

Effect of PSMA PET/CT on the Use of Bone Scintigraphy for Prostate Cancer at a University Hospital System.

We observed at our university-based imaging centers that when prostate-specific membrane antigen (PSMA) PET/CT became available for staging and restaging prostate cancer, the volume of bone scanning on patients with prostate cancer (BS-P) markedly decreased. We aimed to study use patterns of PSMA PET/CT and BS-P at our imaging centers during the 4-y period around U.S. Food and Drug Administration approval of PSMA PET/CT in December 2020. We tested the hypothesis that the rate of decline of BS-P accelerated after U.S. Food and Drug Administration approval, as physicians planned for use of PSMA PET/CT in their patients. Methods: Our clinical report system was searched for BS-P and PSMA PET/CT scans from January 2019 through June 2023. Numbers of scans were tabulated by quarter and year. Quantitative and statistical analyses were performed. Results: Annualized average monthly BS-P peaked at 53.7 scans/mo in 2021 and then decreased over time. There were 552 BS-Ps performed in 2019, 503 in 2020, 614 in 2021, 481 in 2022, and 152 in the first half of 2023. BS-P monthly averages declined by 22% from 2021 to 2022 and by 36% from 2022 to 2023, whereas monthly PSMA PET/CT scan averages increased by 1,416% from 2021 to 2022 and by 69% from 2022 to 2023. There was a significantly greater decline in BS-Ps from 2022 to 2023 than from 2021 to 2022 (36% vs. 22%, P < 0.0001). There were 30 PSMA PET/CT scans performed in 2021, 455 in 2022, and 384 in the first half of 2023. The greatest quarterly increase in these scans (400%) occurred at the outset of PSMA PET/CT implementation in quarter 4 of 2021. In quarter 2 of 2023, the percentage of total studies was higher for PSMA PET/CT than for BS-P (74% vs. 26%, P < 0.0001). Conclusion: At our university-based imaging centers, use of BS-P has declined in correlation with the timing of U.S. Food and Drug Administration approval and implementation of PSMA PET/CT. This study illustrates one instance of workflow changes that occur in the nuclear medicine clinic when new agents are introduced and affect clinical management options.

Evaluation of Gallium-68 prostate-specific membrane antigen, positron emission tomography/computed tomography (GA-68 PSMA PET/CT) in recurrent prostate cancer: a retrospective review of initial clinical experience at Tygerberg Hospital.

Introduction: prostate cancer recurrence after definitive therapy for organ-confined disease often manifests as rising prostate-specific antigen (PSA) levels without clinically overt disease. 68Gallium prostate-specific membrane antigen, positron emission tomography/computed tomography (68GaPSMA PET/CT) imaging plays a major role in the management of recurrent prostate cancer. The purpose of this study was to assess the positivity rate of 68Ga PSMA PET/CT scans in cases of prostate cancer recurrence, and to compare the results with existing international literature. Methods: a retrospective analysis of 177 68Ga PSMA PET/CT scans of patients with biochemically proven disease recurrence was performed. The possible association of a positive PSMA PET/CT with the PSA level and Gleason score were analyzed. Results: a total of 177 68Ga PSMA PET/CT scans were performed in 163 patients (median age 66 years). Of these, 117 (66%) scans detected the site of disease recurrence. Among patients with PSA 0.2-0.99 ng/ml, 23/49 (47%, p<0.0001) were positive, and 20/35 (57%, p<0.0005) were positive in the group of patients with PSA 1.00-1.99. When PSA values were further categorized into PSA <2 ng/ml and PSA ≥2 ng/ml, detection rates were 49% and 86% respectively (p <0.0001). The scans were positive in 65% of patients with Gleason score of <7, 62% with Gleason score of =7 and 68% with Gleason score >7 (p=0.745). Conclusion: there was an increase in the detection rate with an increase in the PSA. Gleason score was not a predictor of a positive 68Ga PSMA PET/CT scan. 68Ga-PSMA PET/CT should be prioritized in patients with biochemical recurrence with PSA levels >0.2 ng/ml.

Comparison of PSMA immunohistochemistry scoring systems to parametric [18F]PSMA-1007 PET/MRI in primary prostate cancer.

PURPOSE: Quantification of PSMA expression via PSMA PET is well-established, however quantification of PSMA via immunohistochemistry (IHC) is not standardized. Our aim was to determine the most optimal PSMA IHC scoring system to quantify PSMA expression with PSMA PET as reference standard. METHODS: Primary intermediate- and high-risk prostate cancer patients received an [18F]PSMA-1007 PET/MRI followed by radical prostatectomy. SUVmax, SUVmean and Ki of the prostate tumor was determined. Prostate tumors were stained with anti-PSMA antibodies and scored by 2 readers via 10 IHC scoring systems: histochemical score (H-score), immunoreactivity scorepredominant intensity (IRSpredominant intensity), IRS classificationpredominant intensity, IRSmean intensity, IRS classificationmean intensity, Allred score, predominant expression pattern, Shannon diversity index (SDI), percentage negatively stained cells and total percentage positively stained cells. Spearman's rank correlation coefficients (ρ) were calculated between PET parameters and IHC scoring systems. Interreader agreement for the IHC scoring systems was measured by the intraclass correlation coefficient (ICC). RESULTS: Fifty tumors in 46 patients were analysed. H-score had the best correlation with SUVmax (ρ 0.615 p < 0.0001) and SUVmean (ρ 0.570, p < 0.0001) and the second best correlation with Ki (ρ 0.411, p = 0.0030). SDI had the best correlation with Ki (ρ -0.440, p = 0.0014) and the second best correlation with SUVmax (ρ -0.516, p = 0.0001) and SUVmean (ρ -0.490, p = 0.0003). A moderate interreader agreement was observed for H-score (ICC 0.663, 95% CI 0.495-0.797) and SDI (ICC 0.546, 95% CI 0.354-0.725). CONCLUSION: H-score had the best correlation with PSMA PET quantification and an acceptable interreader agreement. Therefore, we deem H-score the most optimal PSMA IHC scoring system.

Evaluating the Initial Experience and Clinical Impact of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) Scans in Prostate Cancer Management: A Retrospective Study in Iraq.

Background Prostate cancer is a significant health concern globally, especially in the Middle East, including Iraq. This study explores the adoption and impact of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) scans in Erbil, Iraq, from 2020 to 2023, marking a pivotal advancement in prostate cancer diagnostics in a region where the disease's prevalence is rising.  Materials and methods Through a retrospective analysis at Medya Diagnostic Center in Erbil, Iraq, involving 172 patients, we assessed the feasibility, applicability, and clinical utility of PSMA PET/CT in the local population.  Results The study highlights the modality's enhanced sensitivity and specificity in detecting prostate cancer and its metastases, with bone being the most frequent metastasis site. Despite positive outcomes, challenges such as integration into clinical practice, adherence to guidelines, and financial implications were identified. The majority of referrals came from medical oncologists, primarily for staging and response evaluation, indicating PSMA PET/CT's critical role in managing prostate cancer. The findings suggest a need for national guidelines, interdisciplinary collaboration, and educational initiatives to optimize the use of PSMA PET/CT in Iraq's healthcare setting.  Conclusions This study contributes valuable insights into the early experiences with PSMA PET/CT, paving the way for improved prostate cancer diagnostics and management in similar contexts.

The Relationship between D'Amico and ISUP Risk Classifications and 68Ga-PSMA PET/CT SUVmax Values in Newly Diagnosed Prostate Cancers.

INTRODUCTION: This study aimed to evaluate the relationship between pathological and clinical risk classifications in newly diagnosed prostate cancer patients, and 68Ga-PSMA PET/CT data and serum Prostate Specific Antigen (PSA) values. METHOD: A total of 203 patients who were diagnosed with prostate cancer between 2019 and 2023, who had not yet received treatment and who underwent 68Ga-PSMA PET/CT for staging purposes were included in this study. RESULTS: There was a substantial correlation between D'Amico risk classification, Gleason score, ISUP classification, and the presence or absence of metastasis (p < 0.0001). The median SUVmax value of the prostate gland and the D'Amico risk classification were statistically significantly correlated. (p < 0.0001). There was a statistically significant correlation between the ISUP classification and the PSA value and prostate gland SUVmax value (p < 0.0001). There was a significant correlation between the median SUVmax values of the prostate gland at the time of diagnosis and the patients with and without metastases (p < 0.0001). According to the data obtained from ROC analysis, patients with prostate gland SUVmax values of 8.75 and above were found to have a high probability of metastasis with a sensitivity of 78.9% and a specificity of 59.05%. CONCLUSION: Our study showed that 68Ga-PSMA PET/CT is a highly effective method for staging newly diagnosed high-risk prostate cancer. The probability of metastasis was found to be dramatically increased in Gleason 8 and above. According to D'Amico risk classification, metastasis was detected in at least half of high-risk patients. Since the sensitivity of metastasis was 78.9% in patients with prostate gland SUVmax value above 8.75, we think that these patients should be carefully reported in terms of metastasis.

A Machine Learning Approach for Predicting Biochemical Outcome After PSMA-PET-Guided Salvage Radiotherapy in Recurrent Prostate Cancer After Radical Prostatectomy: Retrospective Study.

BACKGROUND: Salvage radiation therapy (sRT) is often the sole curative option in patients with biochemical recurrence after radical prostatectomy. After sRT, we developed and validated a nomogram to predict freedom from biochemical failure. OBJECTIVE: This study aims to evaluate prostate-specific membrane antigen-positron emission tomography (PSMA-PET)-based sRT efficacy for postprostatectomy prostate-specific antigen (PSA) persistence or recurrence. Objectives include developing a random survival forest (RSF) model for predicting biochemical failure, comparing it with a Cox model, and assessing predictive accuracy over time. Multinational cohort data will validate the model's performance, aiming to improve clinical management of recurrent prostate cancer. METHODS: This multicenter retrospective study collected data from 13 medical facilities across 5 countries: Germany, Cyprus, Australia, Italy, and Switzerland. A total of 1029 patients who underwent sRT following PSMA-PET-based assessment for PSA persistence or recurrence were included. Patients were treated between July 2013 and June 2020, with clinical decisions guided by PSMA-PET results and contemporary standards. The primary end point was freedom from biochemical failure, defined as 2 consecutive PSA rises >0.2 ng/mL after treatment. Data were divided into training (708 patients), testing (271 patients), and external validation (50 patients) sets for machine learning algorithm development and validation. RSF models were used, with 1000 trees per model, optimizing predictive performance using the Harrell concordance index and Brier score. Statistical analysis used R Statistical Software (R Foundation for Statistical Computing), and ethical approval was obtained from participating institutions. RESULTS: Baseline characteristics of 1029 patients undergoing sRT PSMA-PET-based assessment were analyzed. The median age at sRT was 70 (IQR 64-74) years. PSMA-PET scans revealed local recurrences in 43.9% (430/979) and nodal recurrences in 27.2% (266/979) of patients. Treatment included dose-escalated sRT to pelvic lymphatics in 35.6% (349/979) of cases. The external outlier validation set showed distinct features, including higher rates of positive lymph nodes (47/50, 94% vs 266/979, 27.2% in the learning cohort) and lower delivered sRT doses (<66 Gy in 57/979, 5.8% vs 46/50, 92% of patients; P<.001). The RSF model, validated internally and externally, demonstrated robust predictive performance (Harrell C-index range: 0.54-0.91) across training and validation datasets, outperforming a previously published nomogram. CONCLUSIONS: The developed RSF model demonstrates enhanced predictive accuracy, potentially improving patient outcomes and assisting clinicians in making treatment decisions.

Imaging in Renal Cell Carcinoma Detection.

INTRODUCTION: Imaging in renal cell carcinoma (RCC) is a constantly evolving landscape. The incidence of RCC has been rising over the years with the improvement in image quality and sensitivity in imaging modalities resulting in "incidentalomas" being detected. We aim to explore the latest advances in imaging for RCC. METHODS: A literature search was conducted using Medline and Google Scholar, up to May 2024. For each subsection of the manuscript, a separate search was performed using a combination of the following key terms "renal cell carcinoma", "renal mass", "ultrasound", "computed tomography", "magnetic resonance imaging", "18F-Fluorodeoxyglucose PET/CT", "prostate-specific membrane antigen PET/CT", "technetium-99m sestamibi SPECT/CT", "carbonic anhydrase IX", "girentuximab", and "radiomics". Studies that were not in English were excluded. The reference lists of selected manuscripts were checked manually for eligible articles. RESULTS: The main imaging modalities for RCC currently are ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Contrast-enhanced US (CEUS) has emerged as an alternative to CT or MRI for the characterisation of renal masses. Furthermore, there has been significant research in molecular imaging in recent years, including FDG PET, PSMA PET/CT, 99mTc-Sestamibi, and anti-carbonic anhydrase IX monoclonal antibodies/peptides. Radiomics and the use of AI in radiology is a growing area of interest. CONCLUSIONS: There will be significant change in the field of imaging in RCC as molecular imaging becomes increasingly popular, which reflects a shift in management to a more conservative approach, especially for small renal masses (SRMs). There is the hope that the improvement in imaging will result in less unnecessary invasive surgeries or biopsies being performed for benign or indolent renal lesions.

Efficacy and Toxicity of [177Lu]Lu-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: Results from the U.S. Expanded-Access Program and Comparisons with Phase 3 VISION Data.

The phase 3 VISION trial demonstrated that [177Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]-positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor-signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [177Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [177Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using t testing of proportions and survival analyses. Results: In total, 117 patients with mCRPC who received [177Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA RRs (42% vs. 46%; P = 0.50) and OS (median: 15.1 vs. 15.3 mo; P > 0.05). Conclusion: Patients with PSMA-positive mCRPC who received [177Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.

Pretherapeutic PSMA PET-Derived Semiquantitative Parameters as Predictors of PSA Response in Patients with mCRPC Receiving [ 177 Lu]Lu-PSMA-617 Radioligand Therapy.

Objective [ 177 Lu]Lu-prostate-specific membrane antigen (PSMA)-617 radioligand therapy (RLT) shows promise for metastatic castration-resistant prostate cancer (mCRPC) patients with positive PSMA positron emission tomography (PET) imaging. Identifying high-risk patients is crucial. We evaluated pretherapeutic PSMA PET-derived parameters to predict prostate-specific antigen (PSA) response in patients undergoing [ 177 Lu]Lu-PSMA-617 RLT. Materials and Methods We conducted a retrospective analysis among 27 patients (mean age: 71.0 ± 9.5 years; range: 52-85 years) who underwent PSMA PET/computed tomography (CT) and subsequent [ 177 Lu]Lu-PSMA-617 RLT between March 2019 and January 2023. After excluding patients with liver metastases, the number of patients left for analysis was 21 (14 responders and 7 nonresponders). Tumors were semiautomatically delineated with calculation of total tumor volume (PSMA-TV), lesion uptake (PSMA-TLU = PSMA-TV * standardized uptake value [SUV]mean), and lesion quotient (PSMA-TLQ = PSMA-TV/SUVmean) for each patient. Semiquantitative parameters were analyzed only in patients with mCRPC and no liver metastasis. Results In total, 17/27 patients (62.96%) had a decline in PSA levels; 15/27 patients (55.56%) experienced a decline of > 50%. Pretherapeutic PSMA PET/CT results revealed significant differences in PSMA-TV ( p = 0.003), PSMA-TLU ( p = 0.013), and PSMA-TLQ ( p = 0.011) between responders and nonresponders. SUVmax was significantly correlated to the best percentage change in PSA response after 177 Lu-PSMA-617 treatment ( r = -0.79, p = 0.006). No association was observed between PSMA-TV ( p = 0.367), PSMA-TLU ( p = 0.128), and PSMA-TLQ ( p = 0.556), with the best percentage change in PSA response after 177 Lu-PSMA-617 therapy. Conclusion Pretherapeutic PSMA PET-derived PSMA-TV, PSMA-TLU, and PSMA-TLQ were significant negative predictors of PSA response in patients with mCRPC and no liver metastasis receiving [ 177 Lu]Lu-PSMA-617 RLT.