Diagnostic performance of PSMA PET/CT, multiparametric MRI, and combined imaging for local prostate cancer recurrence after radical prostatectomy.

Invited Commentary: Changing Landscape of Imaging in Recurrent Prostate Cancer.

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

INTRODUCTION: Prostate cancer (PCa) is one of the most common cancer diseases. Approximately 30% of patients undergoing radical prostatectomy develop biochemical recurrence within the first 2 years after completion of treatment. One of the leading and available methods for diagnosing local recurrence of prostate cancer is multiparametric magnetic resonance imaging (mpMRI).OBJECTIVE: To determine the effectiveness of mpMRI in detecting local recurrence of PCa in patients after radical prostatectomy (RP) with different levels of total prostate-specific antigen (tPSA).MATERIALS AND METHODS: mpMRI of the pelvis was performed in 118 patients with biochemical relapse of PCa. The criteria for inclusion of patients in the retrospective study were the absence of previous radiation and hormonal therapy. Patients with positive surgical margins were excluded from the study. 46 patients were at low risk of PCa progression, 38 patients were at intermediate risk, and 34 patients were at high risk. Median obPSA 1.72 ng/ml (range 0.22 to 22.19 ng/ml). Median biochemical relapse 11 months. Patients were divided into groups depending on the level of obPSA (I group 0.2–0.5 ng/ml; II group 0.5–1.0 ng/ml; III group 1.0–3.0 ng/ml; IV group more than 3.0 ng/ml). Interpretation of the results was carried out according to the unified reporting system for assessing local recurrence of prostate cancer in patients after RP and RT — prostate imaging recurrence reporting (PI-RR). The probability of local recurrence of prostate cancer depending on the level of obPSA was analyzed using a statistical logistic regression model.DISCUSSION: Early diagnosis of PCa recurrence includes the need to identify local or distant recurrence, determine its volume and precise localization. mpMRI is highly effective in patients with BCR after RP with a total PSA level of more than 1 ng/ml. With a lower PSA level, the percentage of local recurrence detection is lower, which may be due to the small size of the recurrent lesion. In patients with biochemical recurrence of PCa, when mpMRI data indicate a low or uncertain probability of recurrence (PI-RR 1, 2 and 3), PET/CT with 68Ga-PSMA is recommended to exclude distant and regional metastases, as well as as an additional diagnostic method for detecting local recurrence of PCa.CONCLUSION: mpMRI is a highly effective diagnostic method for biochemical recurrence of prostate cancer, which allows for a personalized approach to further treatment. A significant relationship was found between the level of total PSA and the probability of detecting local recurrence according to mpMRI data. Local recurrence of prostate cancer is most often detected at a PSA level above 1 ng/ml, with a sensitivity of 91.8% and a specificity of 88.9%. With a lower value of total PSA, sensitivity and specificity decrease. With a recurrence focus value of ≥7.8 mm, local recurrence is confirmed in 90.4% of patients with subsequent histological examination.

Head-to-head comparison of prostate-specific membrane antigen positron emission tomography/computed tomography and multiparametric magnetic resonance imaging in the detection of biochemical recurrence of prostate cancer: a systematic review and meta-analysis

The Prostate Imaging for Recurrence Reporting (PI-RR) system has been recently proposed to promote standardisation in the MR assessment of prostate cancer (PCa) local recurrence after radical prostatectomy (RP) and radiation therapy (RT). This study aims to evaluate PI-RR's diagnostic accuracy, assess the inter-observer reliability among readers with variable experience, and correlate imaging results with anatomopathological and laboratory parameters. Patients who underwent a pelvic MRI for suspicion of PCa local recurrence after RP or RT were retrospectively enrolled (October 2017-February 2020). PI-RR scores were independently assessed for each patient by five readers with variable experience in prostate MRI (two senior and three junior radiologists). Biochemical data and histopathological features were collected. The reference standard was determined through biochemical, imaging, or histopathological follow-up data. Reader's diagnostic performance was assessed using contingency tables. Cohen's kappa coefficient (κ) and intraclass correlation coefficient (ICC) were calculated to measure inter-observer reliability. The final cohort included 120 patients (median age, 72years [IQR, 62-82]). Recurrence was confirmed in 106 (88.3%) patients. Considering a PI-RR score ≥ 3 as positive for recurrence, minimum and maximum diagnostic values among the readers were as follows: sensitivity 79-86%; specificity 64-86%; positive predictive value 95-98%; negative predictive value 33-46%; accuracy 79-87%. Regardless of reader's level of experience, the inter-observer reliability resulted good or excellent (κ ranges across all readers: 0.52-0.77), and ICC was 0.8. Prostate-specific antigen (PSA) velocity, baseline-PSA, and trigger-PSA resulted predictive of local recurrence at imaging. The PI-RR system is an effective tool for MRI evaluation of PCa local recurrence and facilitates uniformity among radiologists. This study confirmed the PI-RR system's good diagnostic accuracy for the MRI evaluation of PCa local recurrences. It showed high reproducibility among readers with variable experience levels, validating it as a promising standardisation tool for assessing patients with biochemical recurrence. • In this retrospective study, the PI-RR system revealed promising diagnostic performances among five readers with different experience (sensitivity 79-86%; specificity 64-86%; accuracy 79-87%). • The inter-observer reliability among the five readers resulted good or excellent (κ ranges: 0.52-0.77) with an intraclass correlation coefficient of 0.8. • The PI-RR assessment score may facilitate standardisation and generalizability in the evaluation of prostate cancer local recurrence among radiologists.

To validate the role of 3-T diffusion-weighted imaging (DWI) in the detection of local prostate cancer recurrence after radical prostatectomy (RP). T2-weighted imaging, DWI and dynamic contrast-enhanced MRI (DCE-MRI) were performed with a 3-T magnet in 262 patients after RP. Twenty out of 262 patients evaluated were excluded. MRI results were validated by prostate-specific antigen (PSA) reduction after external beam radiotherapy in group A (126 patients, local recurrence size range 4-8 mm) and by transrectal ultrasound biopsy in group B (116 patients, local recurrence size range 9-15 mm). In group A combined T2-weighted and DCE-MRI (T2+DCE) shows 98 % sensitivity, 94 % specificity and 93 % accuracy in identifying local recurrence; combined T2-weighted and DWI with a b value of 3,000 s/mm(2) (T2+DW3) displays 97 % sensitivity, 95 % specificity and 92 % accuracy, while with a b value of 1,000 s/mm(2) (T2+DW1) affords 93 % sensitivity, 89 % specificity and 88 % accuracy. In group B T2+DCE shows 100 % sensitivity, 97 % specificity and 91 % accuracy in detecting local cancer recurrence; T2+DW3 displays 98 % sensitivity, 96 % specificity and 89 % accuracy; T2+DW1 has 94 % sensitivity, 92 % specificity and 86 % accuracy. DCE-MRI is the most reliable technique in detecting local prostate cancer recurrence after RP, though DWI can be proposed as a reliable alternative. • Diffusion-weighted magnetic resonance imaging (DWI-MRI) is being increasingly used in oncology. • PSA analysis does not distinguish prostate cancer recurrence from distant metastasis. • DWI-MR can diagnose local prostate cancer recurrence after radical prostatectomy. • DWI-MR is almost comparable to DCE-MRI in detecting local recurrence.

Background and objectiveOwing to the greater use of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after robot-assisted radical prostatectomy (RARP), patient selection for local salvage radiation therapy (sRT) has changed. Our objective was to determine the short-term efficacy of sRT in patients with BCR after RARP, and to develop a novel nomogram predicting BCR-free survival after sRT in a nationwide contemporary cohort of patients who underwent PSMA PET/CT before sRT for BCR of PCa, without evidence of metastatic disease. MethodsAll 302 eligible patients undergoing PCa sRT in four reference centers between September 2015 and August 2020 were included. We conducted multivariable logistic regression analysis using a backward elimination procedure to develop a nomogram for predicting biochemical progression of PCa, defined as prostate-specific antigen (PSA) ≥0.2 ng/ml above the post-sRT nadir within 1 yr after sRT. Key findings and limitationsBiochemical progression of disease within 1 yr after sRT was observed for 56/302 (19%) of the study patients. The final predictive model included PSA at sRT initiation, pathological grade group, surgical margin status, PSA doubling time, presence of local recurrence on PSMA PET/CT, and the presence of biochemical persistence (first PSA result ≥0.1 ng/ml) after RARP. The area under the receiver operating characteristic curve for this model was 0.72 (95% confidence interval 0.64–0.79). Using our nomogram, patients with a predicted risk of >20% had a 30.8% chance of developing biochemical progression within 1 yr after sRT. ConclusionsOur novel nomogram may facilitate better patient counseling regarding early oncological outcome after sRT. Patients with high risk of biochemical progression may be candidates for more extensive treatment. Patient summaryWe developed a new tool for predicting cancer control outcomes of radiotherapy for patients with recurrence of prostate cancer after surgical removal of their prostate. This tool may help in better counseling of these patients with recurrent cancer regarding their early expected outcome after radiotherapy.

Management of patients with rising prostate-specific antigen after radical prostatectomy

The Role of Prostate-specific Membrane Antigen Positron Emission Tomography for Assessment of Local Recurrence and Distant Metastases in Patients with Biochemical Recurrence of Prostate Cancer After Definitive Treatment: A Systematic Review and Meta-analysis.

The optimal management of biochemical recurrence (BCR) after radical prostatectomy (RP) remains controversial, particularly in the absence of clinical or radiographic evidence of disease. Salvage radiotherapy (SRT) remains standard of care, but it is unclear whether SRT benefits patients when modern imaging with a multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT) are negative for local recurrence. Retrospective data comparing SRT to observation for such patients is fraught with selection bias, underscoring the need for a prospective randomised controlled trial. The Biochemical Recurrence Irradiation or Observation (BRIO) is a randomised study under the DIVINE trial framework (NCT06378866) enrolling men with BCR (prostate-specific antigen [PSA] level ≥0.2, up to 1.5 ng/mL) after RP with no radiographic evidence of recurrence on mpMRI and PSMA-PET/CT. Major inclusion criteria include age ≥18 years, biochemically recurrent prostate cancer after RP with a PSA level between 0.2 and 1.5 ng/mL, and no local or metastatic recurrence on imaging. A total of 312 patients will be enrolled. Participants are randomised 1:1 to standard-of-care SRT followed by surveillance (Group A), or initial observation with subsequent image-guided therapy at radiographic progression (Group B). Based on historical analysis, a total of 30 metastasis events provides 80% power to detect a significant improvement (hazard ratio 0.5 corresponding to a 5-year metastasis-free proportion of 80.7% in the control group and 89.8% in the experimental group with one-sided type I error rate of 0.15). All participants undergo baseline blood collection to measure prostate cancer-extracellular vesicles and cell-free DNA for biomarker development. Participants are followed in a 16-week cycle with serial PSA measurements, repeat imaging if PSA doubles, safety assessment, and patient-reported outcomes. The primary endpoint is distant recurrence-free survival at 5-years using a 12-month landmark to mitigate bias arising from differing assessment schedules for patients receiving optional 6 months of androgen deprivation therapy. Key secondary outcomes include time to hormone therapy, quality of life measures, adverse effects, and novel blood and urine biomarkers. The BRIO study will clarify the clinical benefit of immediate SRT vs observation with image-guided intervention in mpMRI and PET-negative BCR after RP.

MP10-05 UTILITY OF MRI AND TARGETED BIOPSY TO DIAGNOSE LOCAL CANCER RECURRENCE AFTER PROSTATECTOMY

BackgroundThe multiparametric magnetic resonance imaging (mpMRI)-based Prostate Imaging for Recurrence Reporting (PI-RR) system has been proposed to evaluate local recurrence in patients with prostate cancer (PCa) who have been treated with radiation therapy (RT) or radical prostatectomy (RP).PurposeTo evaluate the diagnostic performance and interreader agreement of the PI-RR system in the diagnosis of locally recurrent PCa remains.Material and MethodsA total of 110 patients who have biochemically recurrent PCa after RT (n = 35) or RP (n = 75) were included in this retrospective study. All patients underwent mpMRI, PSMA-PET/CT, and biopsy. Four radiologists with varying levels of expertise independently assessed the local recurrence of PCa using PI-RR. The reference standard was the biopsy pathology. The receiver operating characteristic (ROC) curve was used to evaluate the performance of PI-RR and PSMA-PET/CT, and areas under the ROC curve (AUC) were calculated. Interreader agreement across four readers was evaluated using the intraclass correlation coefficient (ICC).ResultsAmong 110 patients with biochemically recurrent PCa, 28 had local recurrence and 82 had no local recurrence. Using a cutoff of 4, the AUCs of PI-RR in the diagnosis of local recurrence were in the range of 0.61-0.84 in patients treated with RT and 0.71-0.89 in patients treated with RP. The ICC was 0.86 (95% confidence interval = 0.81-0.91).ConclusionPI-RR using a cutoff of 4 has a favorable diagnostic performance and interreader agreement, which might be alternatively used for detecting local recurrence in patients with biochemically recurrent PCa treated with RT or RP.

e17146 Background: Prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA/PET CT) has become the gold standard for staging primary prostate cancer and restaging biochemical recurrent cancer, surpassing magnetic resonance imaging (MRI). However, the role of PSMA/PET CT after radical prostatectomy in localizing the local recurrence of prostate cancer remains unclear. Two studies suggest that MRI yields a higher sensitivity for detecting local recurrence. We aim to further investigate the detectability of the local recurrence of prostate cancer after prostatectomy with PSMA/PET CT versus MRI. Methods: Cases of post-prostatectomy patients with and without local recurrent prostate cancer who received both MRI and PSMA/PET CT imaging were collected. Four radiologists reviewed each case in two phases. In the first phase MRI images were reviewed, while PSMA/PET CT images were reviewed in the second. Each phase was randomized and conducted one month apart to minimize recall. The accuracy, sensitivity, specificity, positive and negative predictive value (PPV, NPV) were calculated. Fleiss’ Kappa scores were used to determine inter-rater reliability. Generalized estimating equations were performed. Results: 37 cases of post-prostatectomy patients who received both PSMA/PET CT and MRI imaging were collected; 23 cases were considered positive for the local recurrence of prostate cancer by our institution’s Tumor Board. When using MRI, radiologists had an accuracy of 73.7%, with a sensitivity of 77.2%, a specificity of 73.1%, a PPV of 83.5%, and a NPV of 64.4%. With PSMA PET/CT, the diagnostic accuracy decreased to 66.2% (p = 0.17). PSMA/PET CT had a lower sensitivity of 65.2%, but an equal specificity of 73.1%. The PPV (81.1%) and NPV (54.3%) were lower with PSMA/PET CT. Of the four radiologists participating in our study, two had a higher accuracy with MRI, while another had a higher accuracy with PSMA/PET CT, and the fourth had an equal accuracy with both imaging methods. PSMA/PET CT showed greater inter-rater reliability than MRI (Fleiss’ Kappa score of 0.36 versus 0.22). Conclusions: MRI showed a non-statistically significant superior diagnostic performance compared to PSMA/PET CT in identifying the local recurrence of prostate cancer in patients treated with prostatectomy. However, only two of four radiologists achieved a higher accuracy when reviewing MRI studies. PSMA/PET CT also had an equal specificity and a greater inter-rater reliability, suggesting both imaging techniques may be valuable in identifying prostate cancer recurrence.

Introduction and ObjectivesTo investigate outcomes of patients with biochemical or local recurrence, without distant metastasis, who received radiation therapy targeting the prostate bed at our hospital following radical prostatectomy for prostate cancer.MethodsPatients suspected of recurrence after radical prostatectomy, indicated by an increase in PSA levels or other factors, were evaluated through imaging tests for local recurrence and distant metastasis. Those who showed no local recurrence received salvage radiotherapy to the prostate bed at a dose of 64.8 Gy. Patients with local recurrence received radiotherapy of 70.8 Gy to the site of local recurrence and 64.8 Gy to the prostate bed.ResultsAmong 19 cases of local recurrence following radical prostatectomy, three out of nine patients who did not receive ADT experienced recurrence after local radiation therapy. In contrast, none of the ten patients who received ADT during radiation therapy experienced recurrence following treatment. No significant difference was observed in clinical recurrence-free survival between patients receiving radiation therapy alone and those receiving ADT during radiation therapy. (p = 0.302) Fifty-six of the 57 patients without local recurrence were evaluated regarding their PSA doubling time (PSADT). Those with a PSADT of 6 months or more at the time of recurrence following radical prostatectomy tended to show longer clinical recurrence-free survival after local radiation therapy compared with showing PSADT of less than 6 months. (p=0.06) Patients with local recurrence who were treated with escalated radiation doses did not show any difference in the incidence of radiotherapy-related gastrointestinal toxicity compared with patients without local recurrence.ConclusionAlthough this study was conducted at a single institution with a small sample size and a limited number of patients, ADT may be beneficial in preventing recurrence following radiation therapy for local recurrence after radical prostatectomy. When considering salvage radiation therapy for patients with biochemical recurrence following radical prostatectomy, PSADT may be useful.

To assess the diagnostic performance of Prostate Imaging for Recurrence Reporting (PI-RR) system using 68 Ga prostate-specific membrane antigen (PSMA)-11 (HBED-CC) PET/MRI in prostate cancer (PCa) patients with biochemical recurrence (BCR). PET/MRI data of 31 PCa patients [17 with radical prostatectomy (RP) and 14 with radiotherapy (RT)] with BCR were retrospectively analyzed. All patients underwent PSMA PET/MRI and multiparametric prostate MRI (mpMRI). Images were evaluated using PI-RR system for mpMRI and the European Association of Nuclear Medicine standardized reporting guidelines (E-PSMA) for PET, with PI-RR and E-PSMA scores dichotomized as ≤2 negative and ≥3 positive for recurrence. Diagnostic performances were assessed using expert-based ground truth establishment. Sensitivity, specificity, and accuracy were 64.7%, 85.7%, and 74.2%, respectively, for PET and 70.6%, 100%, and 83.9%, respectively, for PI-RR. While PI-RR did not reveal any false positive lesions, five patients with false negative PI-RR results were also negative with PET. In patients with RP, sensitivity, specificity, and accuracy were 44.4%, 100%, and 70.6%, respectively, for PET and 55.6%, 100%, and 76.5%, respectively, for PI-RR. For patients with RT, these values were 87.5%, 66.7%, and 78.6%, respectively, for PET and 87.5%, 100%, and 92.9%, respectively, for PI-RR. There was no significant performance difference between PET or PI-RR in all patients ( P = 0.564), patients with RP ( P = 0.317), or RT ( P = 0.157). 68 Ga PSMA PET evaluation with E-PSMA and mpMRI interpretation with PI-RR have similar diagnostic performance for detection of local recurrence after RP or RT in PCa.