PSMA-PET- and MRI-Based Focal Dose Escalated Radiation Therapy of Primary Prostate Cancer: Planned Safety Analysis of a Nonrandomized 2-Armed Phase 2 Trial (ARO2020-01)

Zamboglou, Constantinos; Spohn, Simon K B; Ruf, Prof. Juri; Benndorf, Matthias; Gainey, Mark; Kamps, Marius; Jilg, Prof. Cordula; Gratzke, Prof. Christian; Adebahr, S.; Schmidtmayer-Zamboglou, Barbara; Mix, Prof. Michael; Bamberg, Prof. Fabian; Zschaeck, Sebastian; Ghadjar, Pirus; Baltas, Prof. Dimos; Grosu, Prof. Anca L.

doi:10.1016/j.ijrobp.2022.04.020

Cited by 23 publications

(17 citation statements)

References 36 publications

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“…While not discussed in this review, PSMA PET imaging is indicated per the NCCN guidelines in the initial staging of patients with unfavorable intermediate- and high-risk disease. PSMA PET could be used for dose escalation to avid lesions, as per the FLAME study (which used MRI rather than PSMA PET) [ 77 , 78 ], given the high correlation between PET avidity and tumor aggressiveness on histopathology [ 79 , 80 ]. Although results from the PRIMARY clinical trial showed improved sensitivity and negative predictive value for the detection of clinically significant cancer with PSMA PET compared to MRI [ 81 ], it is unclear what added advantage exists for using PSMA PET images alone or in combination with MRI images over MRI alone for focal boosting or even for focal prostate treatments.…”

Section: Discussionmentioning

confidence: 99%

Management of Patients with Recurrent and Metachronous Oligometastatic Prostate Cancer in the Era of PSMA PET

Sabbagh

Mohamad

Lichter

et al. 2022

Cancers

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Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans have higher sensitivity and specificity for detecting lymph nodes or metastatic disease relative to conventional imaging in prostate cancer staging. Since its FDA approval and incorporation into treatment guidelines, the use of PSMA PET has increased in patients undergoing initial staging, those with recurrence after initial definitive treatment, and patients with metastatic disease. Although the early detection of metastatic lesions is changing disease management, it is unclear whether this impact on management translates into clinical benefit. This review will summarize evidence pertaining to the change in patient management due to PSMA PET use and will discuss the implications of PSMA PET on treatment decisions in prostate cancer, particularly in the settings of biochemical recurrence and metachronous oligometastatic disease.

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Section: Discussionmentioning

confidence: 99%

Management of Patients with Recurrent and Metachronous Oligometastatic Prostate Cancer in the Era of PSMA PET

Sabbagh

Mohamad

Lichter

et al. 2022

Cancers

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“…Other strategies to improve contouring accuracy for MRI-visible prostate tumors include involvement of expert radiologists in target delineation and dedicated training for radiation oncologists [12,13]. Alternative imaging modalities like PSMA PET may also prove useful [14][15][16][17][18]. Automated target delineation using artificial intelligence has potential, though these currently still require considerable expert oversight [19,20].…”

Section: Discussionmentioning

confidence: 99%

Clinical Impact of Contouring Variability for Prostate Cancer Tumor Boost

Zhong,

Lui,

Kuznetsova

et al. 2024

Preprint

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Purpose:The focal radiotherapy (RT) boost technique was shown in the FLAME trial to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. The ReIGNITE RT Boost study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists' contour inaccuracies would yield meaningfully worse clinical outcomes.Materials & Methods:44 radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the FLAME trial protocol. Probability of biochemical failure (BF) was determined using a model from the FLAME trial. The primary metric evaluated was delta BF (ΔBF = Participant BF - Expert BF). An absolute increase in BF ≥5% was considered clinically meaningful.Results:8 patient cases and 394 target volumes for focal RT boost planning were included in this analysis. In general, participant plans were associated with worse predicted clinical outcomes compared to the expert plan, with an average absolute increase in BF of 4.3%. 37% of participant plans were noted to have an absolute increase in BF of 5% or more.Conclusion:Radiation oncologists' attempts to contour tumor targets for focal RT boost are frequently inaccurate enough to yield meaningfully inferior clinical outcomes for patients.

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“…In primary prostate cancer, a meta-analysis by Vogelius and Bentzen demonstrated a dose-response association with improved “biochemical no evidence of disease” with radiotherapy doses up to 80 Gy. Recent trials performing focal dose escalation of the dominant intraprostatic lesion achieved benefits in biochemical disease-free survival with doses up to 113.8 Gy . Focal sRT dose escalation to PET-defined local recurrences with higher total doses may thus provide more benefit than dose escalation in the complete prostatic fossa.…”

Section: Discussionmentioning

confidence: 99%

“…PET-CT or PET-magnetic resonance imaging prior to sRT were performed with the following radiotracers: 68 Ga-labeled PSMA-11 (n = 723), 68 Ga-labeled PSMA-I&T (n = 61), 18 F-labeled PSMA-1007 (n = 117), 18 F-labeled PSMA-DCFPyL, 18 F-labeled siPSMA-14, or 18 F-labeled PSMA-rhPSMA-7/-7.3 (n = 128). All scans were performed according to local practice and images were locally interpreted by 2 experienced readers.…”

Section: Psma-pet Scans or Ct Scans Prior To Srtmentioning

confidence: 99%

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Development and Validation of a Multi-institutional Nomogram of Outcomes for PSMA-PET–Based Salvage Radiotherapy for Recurrent Prostate Cancer

et al. 2023

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ImportanceProstate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer.ObjectiveTo develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET–based sRT.Design, Setting, and ParticipantsThis retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022.ExposuresPatients with a detectable post–radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible.Main Outcomes and MeasuresThe FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT.ResultsIn the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (&gt;70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort.Conclusions and RelevanceThis cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET–guided sRT.

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PSMA-PET- and MRI-Based Focal Dose Escalated Radiation Therapy of Primary Prostate Cancer: Planned Safety Analysis of a Nonrandomized 2-Armed Phase 2 Trial (ARO2020-01)

Cited by 23 publications

References 36 publications

Management of Patients with Recurrent and Metachronous Oligometastatic Prostate Cancer in the Era of PSMA PET

Management of Patients with Recurrent and Metachronous Oligometastatic Prostate Cancer in the Era of PSMA PET

Clinical Impact of Contouring Variability for Prostate Cancer Tumor Boost

Development and Validation of a Multi-institutional Nomogram of Outcomes for PSMA-PET–Based Salvage Radiotherapy for Recurrent Prostate Cancer

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