PO63: Optimizing Prostate Cancer Treatment in Men with Advanced Local Disease (OPTiMAL) Study: Initial Multi-Modal Imaging Results

Purpose Optimizing Prostate Cancer Treatment in Men with Advanced Local disease (OPTiMAL) is a single-arm phase II study targeted towards unfavourable risk patients. As a successor to the largest randomized clinical trial (ASCENDE) comparing low-dose-rate prostate brachytherapy (LDR-PB) boost to external beam radiation therapy (EBRT) boost for prostate cancer (PCa) treatment, this study is designed to continue the use of the LDR-PB boost that resulted in high levels of biochemical progression-free survival (b-PFS) in ASCENDE while also aiming to reduce adverse side effects by lowering the overall dose and also limiting high dose regions to identified sites of disease. Materials and Methods The central treatment policy in OPTiMAL is to give 100% of the minimum prescribed brachytherapy dose (mpd) to the whole prostate gland while limiting regions with ≥150% of the mpd−as much as possible−to areas containing PCa as determined from transperineal template-guided mapping biopsy (TTMB). In addition, the mpd has been lowered to 100 Gy relative to the 115 Gy ASCENDE dose, and EBRT is delivered after the implant to enable the implanted seeds to be used for prostate localization on verification images. Treatment also includes androgen deprivation therapy (ADT) between TTMB and implant. An important additional aim of the OPTiMAL study is to use the TTMB results as a “ground truth” for investigating the potential of multi-modal advanced imaging of the prostate to better delineate tumours and target them appropriately during treatment. Imaging modalities included in the study are as follows: (1) multi-parametric magnetic resonance imaging (mpMRI) following a protocol compatible with PI-RADs V2, (2) magnetic resonance elastography (MRE) (in the same mpMRI session), (3) multi-parametric transrectal ultrasound (mpTRUS), including shear wave absolute vibro-elastography imaging (SWAVE), strain elastography, and time-series B-mode, all acquired immediately prior to and with the patient in position for the TTMB. Although OPTiMAL does not specifically use the findings from these multi-modal imaging studies for brachytherapy treatment planning, the potential of these multi-modal images for PCa localization is being studied by comparing the findings with the TTMB results. Biopsy core locations in the prostate are tracked during the procedure using ultrasound imaging and the VariPath module in VariSeed software (Varian Medical Systems, Palo Alto, CA, United States). Once available, pathology findings are allocated to the tracked cores within the VariPath software and then localized in the multi-modal images using intensity and surface-based image registration to the TTMB ultrasound images and labels. Results The OPTiMAL study is ongoing and 11 patients have been enrolled so far with 10 patients fulfilling all requirements for LDR-PB boost treatment. Advanced imaging data have been collected for 5 of the patients. Initial analysis of the elastography data (MRE, SWAVE) indicates a positive correlation with the TTMB ground truth. Fig 1 illustrates the correlation of the TTMB findings with the elastography images for P10. Conclusions Initial analysis suggests that such multi-modal imaging data has the potential to localize tumours reliably which can eventually replace the invasive TTMB procedure altogether. We are currently recruiting more patients and with more imaging and follow-up (relapse rate, side effects endured) data available, a deeper analysis will be conducted. Optimizing Prostate Cancer Treatment in Men with Advanced Local disease (OPTiMAL) is a single-arm phase II study targeted towards unfavourable risk patients. As a successor to the largest randomized clinical trial (ASCENDE) comparing low-dose-rate prostate brachytherapy (LDR-PB) boost to external beam radiation therapy (EBRT) boost for prostate cancer (PCa) treatment, this study is designed to continue the use of the LDR-PB boost that resulted in high levels of biochemical progression-free survival (b-PFS) in ASCENDE while also aiming to reduce adverse side effects by lowering the overall dose and also limiting high dose regions to identified sites of disease. The central treatment policy in OPTiMAL is to give 100% of the minimum prescribed brachytherapy dose (mpd) to the whole prostate gland while limiting regions with ≥150% of the mpd−as much as possible−to areas containing PCa as determined from transperineal template-guided mapping biopsy (TTMB). In addition, the mpd has been lowered to 100 Gy relative to the 115 Gy ASCENDE dose, and EBRT is delivered after the implant to enable the implanted seeds to be used for prostate localization on verification images. Treatment also includes androgen deprivation therapy (ADT) between TTMB and implant. An important additional aim of the OPTiMAL study is to use the TTMB results as a “ground truth” for investigating the potential of multi-modal advanced imaging of the prostate to better delineate tumours and target them appropriately during treatment. Imaging modalities included in the study are as follows: (1) multi-parametric magnetic resonance imaging (mpMRI) following a protocol compatible with PI-RADs V2, (2) magnetic resonance elastography (MRE) (in the same mpMRI session), (3) multi-parametric transrectal ultrasound (mpTRUS), including shear wave absolute vibro-elastography imaging (SWAVE), strain elastography, and time-series B-mode, all acquired immediately prior to and with the patient in position for the TTMB. Although OPTiMAL does not specifically use the findings from these multi-modal imaging studies for brachytherapy treatment planning, the potential of these multi-modal images for PCa localization is being studied by comparing the findings with the TTMB results. Biopsy core locations in the prostate are tracked during the procedure using ultrasound imaging and the VariPath module in VariSeed software (Varian Medical Systems, Palo Alto, CA, United States). Once available, pathology findings are allocated to the tracked cores within the VariPath software and then localized in the multi-modal images using intensity and surface-based image registration to the TTMB ultrasound images and labels. The OPTiMAL study is ongoing and 11 patients have been enrolled so far with 10 patients fulfilling all requirements for LDR-PB boost treatment. Advanced imaging data have been collected for 5 of the patients. Initial analysis of the elastography data (MRE, SWAVE) indicates a positive correlation with the TTMB ground truth. Fig 1 illustrates the correlation of the TTMB findings with the elastography images for P10. Initial analysis suggests that such multi-modal imaging data has the potential to localize tumours reliably which can eventually replace the invasive TTMB procedure altogether. We are currently recruiting more patients and with more imaging and follow-up (relapse rate, side effects endured) data available, a deeper analysis will be conducted.