Dominant Intraprostatic Lesion Research Articles

Stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer – Acute toxicity and patient-reported outcomes in the prospective, multicenter SMILE phase II trial

BackgroundDue to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial. Materials and methodsA total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and gastrointestinal (GI-) toxicity, as defined by CTCAE v. 5.0 and RTOG as well as patient-reported outcomes according to EORTC QLQ-C30 and -PR25 scores were analyzed at completion of radiotherapy, 6 and 12 weeks after radiotherapy and compared to baseline symptoms. ResultsThere were no toxicity-related treatment discontinuations. At the 12-week follow-up visit, no grade 3 + toxicities were reported according to CTCAE. Up until the 12-week visit, in total 16 patients (23 %) experienced a grade 2 GU or GI toxicity. Toxicity rates peaked at the end of radiation therapy and subsided within the 12-week follow-up period. At the 12-week follow-up visit, no residual grade 2 GU toxicities were reported and 1 patient (1 %) had residual grade 2 enteritic symptoms. With exception to a significant improvement in the emotional functioning score following MRgSBRT, no clinically meaningful changes in the global health status nor in relevant subscores were reported. ConclusionDaily online-adaptive MRgSBRT for localized prostate cancer resulted in an excellent overall toxicity profile without any major negative impact on quality of life.

Extreme-hypofractionated RT with concomitant boost to the DIL in PCa: a 5-year update on oncological and patient-reported outcomes for the phase II trial "GIVE ME FIVE".

The present work reports updated oncological results and patients-reported outcomes at 5years of phase II trial "Short-term high precision RT for early prostate cancer with SIB to the dominant intraprostatic lesion (DIL) for patients with early-stage PCa". Data from patients enrolled within AIRC IG-13218 (NCT01913717) trial were analyzed. Clinical and GU/GI toxicity assessment and PSA measurements were performed every 3months for at least 2years after RT end. QoL of enrolled patients was assessed by IPSS, EORTC QLQ-C30, EORTC QLQ-PR25, and IIEF-5. Patients' score changes were calculated at the end of RT and at 1, 12, and 60months after RT. A total of 65 patients were included. At a median follow-up of 5years, OS resulted 86%. Biochemical and clinical progression-free survival at 5years were 95%. The median PSA at baseline was 6.07ng/ml, while at last follow-up resulted 0.25ng/ml. IPSS showed a statistically significant variation in urinary function from baseline (p = 0.002), with the most relevant deterioration 1month after RT, with a recovery toward baseline at 12months (p ≤ 0.0001). A numerical improvement in QoL according to the EORTC QLQ-C30 has been reported although not statistically significant. No change in sexual activity was recorded after RT. The study confirms that extreme hypofractionation with a DIL boost is safe and effective, with no severe effects on the QoL. The increasing dose to the DIL does not worsen the RT toxicity, thus opening the possibility of an even more escalated treatment.

Treatment intensification strategies for men undergoing definitive radiotherapy for high-risk prostate cancer.

Treatment intensification of external beam radiotherapy (EBRT) plays a crucial role in the treatment of high-risk prostate cancer. We performed a critical narrative review of the relevant literature and present new developments in evidence-based treatment intensification strategies. For men with high-risk prostate cancer, there is strong evidence to support prolonging androgen deprivation therapy (ADT) to 18-36months and escalating the dose to the prostate using a brachytherapy boost. A potentially less toxic alternative to a brachytherapy boost is delivering a focal boost to dominant intraprostatic lesions using EBRT. In patients who meet STAMPEDE high-risk criteria, there is evidence to support adding a second-generation anti-androgen agent, such as abiraterone acetate, to long-term ADT. Elective pelvic lymph node irradiation may be beneficial in select patients, though more prospective data is needed to elucidate the group of patients who may benefit the most. Tumor genomic classifier (GC) testing and advanced molecular imaging will likely play a role in improving patient selection for treatment intensification as well as contribute to the evolution of treatment intensification strategies for future patients. Treatment intensification using a combination of EBRT, advanced hormonal therapies, and brachytherapy may improve patient outcomes and survival in men with high-risk prostate cancer. Shared decision-making between patients and multidisciplinary teams of radiation oncologists, urologists, and medical oncologists is essential for personalizing care in this setting and deciding which strategies make sense for individual patients.

Simultaneous Focal Boost With Stereotactic Radiation Therapy for Localized Intermediate- to High-Risk Prostate Cancer: Primary Outcomes of the SPARC Phase 2 Trial

Purpose: Dose escalated radiotherapy is associated with better biochemical control at the expense of toxicity. Stereotactic body radiotherapy (SBRT) with dose escalation to the dominant intraprostatic lesion (DIL) provides a logical approach to improve outcomes in high-risk disease whilst limiting toxicity. This study evaluated the toxicity and quality of life (QOL) with CyberKnife-based SBRT and simultaneous integrated boost in localised prostate cancer. Methods and Materials: Eligible participants included newly diagnosed, biopsy-proven unfavourable intermediate to high risk localised prostate cancer (at least one of the following: Gleason ≥ 4+3, MRI defined T3a N0, PSA ≥ 20) with up to two MRI-identified DILs. Participants received 36.25Gy in 5 fractions on alternative days with a simultaneous boost to DIL up to 47.5Gy as allowed by organs at risk constraints delivered by CyberKnife. All participants received androgen deprivation therapy. The primary outcome measure was acute grade 2 + genitourinary toxicity. Acute and late genitourinary and gastrointestinal toxicity using RTOG scoring, biochemical parameters, IPSS, IIEF5, EQ5D QOL outcomes were assessed. Results: Between 2013 and 2023, 20 participants were enrolled with a median follow-up of 30 months. The median D95 dose to DIL was 47.43Gy. Cumulative acute grade 2 + genitourinary and gastrointestinal toxicity was 25% and 30%, respectively. One patient developed acute grade 3 genitourinary toxicity (5%). There is no late grade 3 genitourinary or gastrointestinal toxicity to date. IPSS score and urinary QOL scores recovered to baseline by 6months. Patient-reported outcomes showed no significant change in EQ-5D QOL scores at 12 weeks and 1 year. There are no cases of biochemical relapse reported to date. Conclusions: CyberKnife SBRT delivered dose of 36.25Gy to the prostate with a simultaneous integrated boost up to 47.5Gy is well tolerated. Acute and late GU and GI toxicity rates are comparable to other contemporary SBRT trials and series with focal boost.

Microboost dose escalation for localized prostate cancer within a statewide radiation oncology quality consortium.

298 Background: The phase III FLAME trial demonstrated that in localized prostate cancer, an external beam radiotherapy (EBRT) simultaneous integrated microboost to an MRI-defined dominant intraprostatic lesion improves biochemical control without affecting toxicity and quality of life. Given the complexity required to deliver high microboost doses, we hypothesized that practice patterns are variable in clinical practice. We aimed to characterize microboost utilization and evaluate dosimetric parameters within the statewide Michigan Radiation Oncology Quality Consortium (MROQC). Methods: Men with intermediate or high-risk prostate adenocarcinoma treated with curative intent radiotherapy for intact disease were included. Data was prospectively collected, including T/N-category, Gleason score, prostate-specific antigen, and percent positive biopsy cores. Full DICOM files were available for dosimetric data. Multivariable analyses (MVA) were used to evaluate associations between receipt of microboost, known prognostic factors, and fiducial marker and rectal spacer placement (advanced image guided radiation therapy (IGRT)). Results: From 10/26/20 to 06/26/23, 741 patients across 26 centers were enrolled, 71% (n=528) with intermediate-risk and 29% (n=213) with high-risk disease. Androgen deprivation therapy was planned in 61%. EBRT + whole-gland brachytherapy boost was utilized in 29% (n=217/741) of patients. Of those treated with EBRT (71%, n=524/741), 10% received a microboost (n = 53/524). Brachytherapy boost and microboost were used in 9 and 7 centers, respectively. Most patients received either conventional fractionation or moderate hypofractionation- 11% and 66% in EBRT without microboost and 21% and 60% with microboost, respectively. Microboost treatment was associated with use of a planning MRI (91% vs. 62%, p <0.0001) as well as fiducial marker and rectal spacer placement (76% vs. 45%, p <0.0001). Median prostate planning target volume (PTV) was smaller in microboost patients (127 cc vs. 91 cc, p = 0.002); median boost volume was 21 cc. Median boost dose (D0.1cc) was 117% (IQR 115% – 119%) of the PTV prescription. Microboost patients had significantly higher mean bladder D1cc[%] (105.7% vs. 103.4%, p = 0.002) and numerically lower rectal D1cc[%] (90.7% vs. 94.1%, p = 0.065). On MVA, receipt of microboost was significantly associated with grade group 4 or 5 disease, planning MRI use, and fiducial and rectal spacer use. Conclusions: Within a large, diverse prospective cohort of men with prostate cancer treated in both academic and community settings, a microboost was utilized in 10% of EBRT cases. Microboost use was associated with higher grade group, MRI planning, and advanced IGRT. EBRT microboost is an emerging dose escalation strategy and further studies confirming safety and improved clinically meaningful outcomes may increase uptake in routine practice.

MR delta-radiomics in prostate cancer: changes in the dominant intraprostatic lesion during different radiotherapy regimens

MR delta-radiomics in prostate cancer: changes in the dominant intraprostatic lesion during different radiotherapy regimens

Proton versus photon therapy for high-risk prostate cancer with dose escalation of dominant intraprostatic lesions: a preliminary planning study.

This study aimed to investigate the feasibility of safe-dose escalation to dominant intraprostatic lesions (DILs) and assess the clinical impact using dose-volume (DV) and biological metrics in photon and proton therapy. Biological parameters defined as late grade ≥ 2 gastrointestinal (GI) and genitourinary (GU) derived from planned (D P) and accumulated dose (D A) were utilized. In total, 10 patients with high-risk prostate cancer with multiparametric MRI-defined DILs were investigated. Each patient had two plans with a focal boost to the DILs using intensity-modulated proton therapy (IMPT) and volumetric-modulated arc therapy (VMAT). Plans were optimized to obtain DIL coverage while respecting the mandatory organ-at-risk constraints. For the planning evaluation, DV metrics, tumor control probability (TCP) for the DILs and whole prostate excluding the DILs (prostate-DILs), and normal tissue complication probability (NTCP) for the rectum and bladder were calculated. Wilcoxon signed-rank test was used for analyzing TCP and NTCP data. IMPT achieved a higher Dmean for the DILs compared to VMAT (IMPT: 68.1 GyRBE vs. VMAT: 66.6 Gy, p < 0.05). Intermediate-high rectal and bladder doses were lower for IMPT (p < 0.05), while the high-dose region (V60 Gy) remained comparable. IMPT-TCP for prostate-DIL were higher compared to VMAT (IMPT: 86%; α/β = 3, 94.3%; α/β = 1.5 vs. VMAT: 84.7%; α/β = 3, 93.9%; α/β = 1.5, p < 0.05). Likewise, IMPT obtained a moderately higher DIL TCP (IMPT: 97%; α/β = 3, 99.3%; α/β = 1.5 vs. VMAT: 95.9%; α/β = 3, 98.9%; α/β = 1.5, p < 0.05). Rectal D A-NTCP displayed the highest GI toxicity risk at 5.6%, and IMPT has a lower GI toxicity risk compared to VMAT-predicted Quantec-NTCP (p < 0.05). Bladder D P-NTCP projected a higher GU toxicity than D A-NTCP, with VMAT having the highest risk (p < 0.05). Dose escalation using IMPT is able to achieve a high TCP for the DILs, with the lowest rectal and bladder DV doses at the intermediate-high-dose range. The reduction in physical dose was translated into a lower NTCP (p < 0.05) for the bladder, although rectal toxicity remained equivalent.

Association between Artificial Intelligence-Derived Tumor Volume and Oncologic Outcomes for Localized Prostate Cancer Treated with Radiation Therapy.

Although clinical features of multi-parametric magnetic resonance imaging (mpMRI) have been associated with biochemical recurrence in localized prostate cancer, such features are subject to inter-observer variability. We evaluated whether the volume of the dominant intraprostatic lesion (DIL), as provided by a deep learning segmentation algorithm, could provide prognostic information for patients treated with definitive radiation therapy (RT). We conducted a retrospective study of 438 patients with localized prostate cancer who underwent an endorectal coil, high B-value, 3-Tesla mpMRI and were treated with definitive RT at our institution between 2010 and 2017. We utilized the publicly available nnUNet to train a segmentation model which was used to identify the DIL. We examined the association between the artificial intelligence (AI)-generated DIL volume and oncologic outcomes, including biochemical recurrence and metastasis risk, using cause-specific Cox regression and time-dependent receiver operating characteristic analysis. The AI model identified DILs with an area under the receiver operating characteristic (AUROC) of 0.827 at the patient level. For the 233 patients with available PI-RADS scores, with a median follow-up of 5.6 years, there were 28 biochemical failures. AI-defined DIL volume was significantly associated with biochemical failure (adjusted hazard ratio 1.60, 95% confidence interval 1.14-2.24, p = 0.007) after adjustment for PI-RADS score. Among all 438 patients with a median follow-up of 6.9 years, there were 49 biochemical failures and 22 metastases. The AUROC for predicting 7-year biochemical failure for AI volume (0.790) was similar to that for National Comprehensive Cancer Network (NCCN) category (p = 0.17). The AUROC for predicting 7-year metastasis for AI volume trended towards being higher compared to NCCN category (0.854 vs 0.769, p = 0.06). An AI algorithm using deep learning could identify the DIL with good performance. AI-defined DIL volume may be able to provide prognostic information independent of the NCCN risk group or other radiologic factors for patients with localized prostate cancer treated with RT.

Indications for Adjuvant Radiation after Radical Prostatectomy as Predicted by Artificial Intelligence-Derived Dominant Intraprostatic Lesion Volume.

In prostate cancer, PI-RADs scores of dominant intraprostatic lesions (DILs) in multi-parametric magnetic resonance imaging (mpMRI) are prognostic; however, their inter-observer agreement is only moderate. Artificial intelligence (AI) may be a powerful tool for prognostication by analyzing a large number of scans consistently in a short amount of time. This study investigated whether the DIL volume (DILvol) provided by an AI deep-learning segmentation algorithm could predict adverse findings at radical prostatectomy (RP), some of which could warrant adjuvant radiation therapy (RT). We conducted a retrospective study of 185 consecutive patients with localized prostate cancer who underwent an endorectal coil, high B-value (> = 1000 s/mm2), 3-Tesla mpMRI followed by RP between 2015 and 2017. Using a previously trained deep learning nnUNet algorithm for providing DIL segmentations from patients treated with definitive RT, we segmented the DIL for the RP cohort. We evaluated the association of AI DILvol with the risks of adverse pathologic factors, including positive margins, pathologic T3 (pT3) disease, and pathologic Gleason (pGS8-10) disease, using separate univariate logistic regression models. We then included AI DILvol, pT3 (vs pT2), pGS8-10 (vs pGS6-7), margin status, and pre-RP PSA for predicting post-RP PSA values utilizing multivariate linear regression analysis. Finally, we included these same factors into a multivariate logistic regression analysis for predicting the risk of meeting adjuvant RT indications (PSA persistence post-RP > = 0.1 ng/mL or positive lymph nodes). The median time between RP and post-PSA value was 1.6 months. The Pearson's correlation coefficient between AI and reference DILvol (sum of manually contoured PI-RADS 3-5 lesions) was 0.86 (p < 0.001). The Pearson's correlation coefficient between AI DILvol and pathologic tumor size was 0.63 (p < 0.001). Utilizing separate univariate logistic regression models, we found that AI DILvol was significantly associated with the risks of positive margins (OR 1.31 [1.10, 1.58]; p = 0.003), pT3 (OR 1.59 [95% CI: 1.30, 1.99]; p < 0.001), and pGS8-10 (OR 1.28 [1.07, 1.56]; p = 0.01). On multivariate linear regression, AI DILvol (0.27/mL [0.25, 0.29]; p < 0.001) was significantly correlated with post-RP PSA values, after controlling for adverse factors and pre-RP PSA. On multivariate logistic regression, AI DILvol (adjusted OR 1.32 [1.05, 1.69]; p = 0.03) was the only factor significantly associated with the risk of meeting adjuvant RT indications after controlling for these same factors. For localized prostate cancer treated with RP, AI DILvol was the only factor significantly associated with the risk of meeting adjuvant RT indications, even after controlling for pathologic factors at RP. Further studies are needed to determine if AI DILvol is prognostic for long-term oncologic outcomes after RP.

Is the Motion Causing a Commotion? Two-Fraction Prostate SBRT on the MR-Linac.

In HERMES (NCT04595019) men with localized prostate cancer are treated on the Unity MR-Linac platform (MRL, Elekta AB, Stockholm) and randomized between stereotactic body radiotherapy (SBRT) with 36.25 Gy in 5 fractions and 24 Gy in 2 fractions. Patients randomized to two fractions receive 24 Gy to the high risk PTV, 20 Gy to the low risk PTV and a boost of 27 Gy to the dominant intraprostatic lesion. This study explores dose received by the target and organs at risk (OARs) when considering intrafraction motion in two fraction SBRT. Targets and OARs were delineated and a reference plan generated on Monaco v5.40.01 (Elekta). An Adapt-to-Shape (ATS) workflow was used. Contours were propagated to the session MRI (MRIsession) and edited accordingly. Prior to delivery, a verification MRI (MRIverif) was acquired with baseline shifts corrected for using the Adapt-to-Position (ATP-of-ATS) workflow. A post treatment MRI (MRIpost) was acquired after delivery. Men in the 2-fraction arm received each fraction in 2 sub-fractions sequentially on the same day, to mitigate intrafraction motion. The plans of 5 men receiving 2 fraction SBRT were analyzed. The targets, urethra, bladder and rectum were recontoured on the MRIverif and MRIpost. Delivered plans were recalculated on the corresponding MRIverif and MRIpost. The percentage of optimal and mandatory target dose constraints met were calculated. Accumulated OAR doses were calculated by averaging their respective dose statistics across all sub-fractions, conservatively assuming that the same area of the OAR receives the maximum dose each fraction. Analysis was carried out separately for MRIverif and MRIpost as the true 'delivered dose' most likely lies between these two estimates. There was good coverage across all fractions. The mandatory constraints of CTVpsv V24.0 Gy > 95% and CTVsv V20.0 Gy > 95% were met in 100% of fractions and V2700cGy > 95% in 90% on the MRIpost. Table 3 shows OAR dose. This work demonstrates that target coverage is good, even for the GTV where no margin is applied. With our conservative dose calculation approach, we found dose constraints are exceeded for some patients. However, treatment has been well tolerated, suggesting that that our current dose constraints may be cautious. Once Elekta's True Tracking and automated gating software is implemented at our center we will be able to further improve OAR clinical goal compliance.

Dosimetric Predictors of Toxicities and Quality of Life Following Two-Fraction Stereotactic Body Radiotherapy for Prostate Cancer.

There is emerging interest in two-fraction stereotactic body radiotherapy (2#SBRT) for localized prostate cancer. However, there is limited data to guide organs at risk (OAR) dose constraints in 2#SBRT. We aim to identify dosimetric predictors of toxicities and quality of life (QoL) using real life patient data from two prospective 2#SBRT trials. We included 60 patients who had 2#SBRT in the 2STAR (NCT02031328) and 2SMART (NCT03588819) phase 2 trials. The prescribed dose was 26Gy to the prostate +/- focal boost of 32Gy to the dominant intraprostatic lesions. Toxicities and QoL data were prospectively collected using CTCAEv4 and EPIC26 questionnaires. For QoL, we reported the minimal clinical important changes (MCIC), defined as changes in QoL score of >0.5 standard deviation from baseline QoL score. We evaluated the bladder, urethra, rectum, and penile bulb dosimetry (urethra dosimetry only available in 30 patients in 2SMART trial). Some of the dosimetric parameters were log-transformed to normalize the distribution. Cox regression was used to identify dosimetric predictors for acute and late grade ≥2 GU toxicities. Logistic regression was used to identify dosimetric predictors for late MCIC in urinary, bowel and sexual QoL domains. Backward stepwise selection was used to identify significant dosimetric parameters. For GU toxicities and urinary QoL, three additional clinical factors (age, prostate volume and IPSS) were included in the final model as confounding factors. Receiver operating characteristics curve was used to identify cut-off for significant dosimetric parameters. The median follow-up for the cohort was 56 months (range: 39-78 months). The cumulative acute and late grade ³2 GU toxicities were 62% (37/60) and 57% (34/60) respectively. No bladder or urethra dosimetric parameter was associated with acute grade ≥2 GU toxicities. Bladder D0.5cc was significant predictor of late grade ≥2 GU toxicities in univariate model (P = 0.05), but not in multivariate model. Baseline IPSS score was the single strongest predictor for late grade ≥2 GU toxicities (HR = 1.9; 95% CI = 1.1-3.4; P = 0.03). For late QoL outcomes, there were 36% (21/58), 28% (16/58), and 29% (17/58) of patients with MCIC in urinary, bowel and sexual QoL domains respectively. Bladder V10Gy was associated with late urinary MCIC in multivariate model after adjusting for clinical confounders (HR = 2.6, 95% CI = 1.1-6.6; P = 0.04). 48% (14/29) and 24% (7/29) of patients with bladder V10Gy>13.9% and V10Gy≤13.9% respectively had late urinary MCIC. No rectum and penile bulb dosimetry parameters was identified to be associated with late bowel or sexual QoL. Using real life patient data from prospective clinical trials with medium term follow-up, we identified statistically significant bladder dosimetry parameter predictive of late urinary QoL. This finding could be useful to guide OAR dose constraints in prostate 2#SBRT trials.

Multifocal MRI-Directed Simultaneous Integrated Boost (SIB) in the Treatment of Prostate Cancer with Stereotactic Body Radiation Therapy (SBRT).

Conventionally fractionated MRI-directed radiation boosts in the treatment of prostate cancer have been shown to improve oncologic outcomes in the FLAME trial. Moreover, recent data has demonstrated local recurrences following SBRT predominately occur at the site of the dominant intraprostatic lesion. Modern protocols including HYPO-Flame have demonstrated early safety profiles of a 5-fraction intraprostatic SBRT boost. This study aims to determine if multifocal SIB treatment is associated with additional acute toxicity relative to unifocal boosts. In this single-center retrospective analysis, we identified all patients who underwent SBRT with a SIB using a robotic radiosurgical platform. Fiducial markers and hydrogel rectal spacers were placed prior to simulation. All patients underwent treatment planning MRI with documented PI-RADS 3-5 lesions targeted for SIB delineation. Patients were treated to a prescription dose of 3500 to 3625 cGy in 5 fractions, or 1800 to 2100 cGy in 3 fractions in concert with pelvic nodal irradiation. The SIB prescription dose ranged from 4000 to 4200 cGy and 2100 to 2300 cGy for the 5- and 3-fraction regimens, respectively. Acute toxicity was defined as that occurring within 60 days of treatment completion using the CTCAE v. 5.0. A total of 35 patients with a median age of 70 underwent SBRT SIB from 5/2022 to 1/2023 with the following risk distribution: low (3%), intermediate (66%), high (28%), and regional (3%). Most patients received rectal spacers (77%) and neoadjuvant ADT (71%) prior to treatment. The majority of patients underwent 5-fraction SBRT (74%) with the remainder receiving SBRT as a boost. Approximately half (51%) of the cohort was treated with a multifocal SIB to multiple PI-RADS lesions. Mean SIB dose was 4105 and 2377 cGy in 5- and 3-fractions, respectively. With a median follow up of 33 days, we identified no grade 3+ acute toxicities. Crude rate of grade 2 GU and GI toxicity was 51% and 6%, respectively, on par with prior unifocal publications. There was no difference in median SIB volume between uni- and multifocal boosts (1.47 vs. 1.72 cc, p = 0.57), nor was SIB volume associated with an increased risk of grade 2 GU toxicity (p = 0.28). Dominant lesion location was not associated with increased grade 2 GU toxicity (p = 0.29). No grade 2 GI toxicities occurred in the multifocal group. Finally, univariate analysis did not identify multifocal boost as a risk of grade 2 GU toxicity (35%) relative to unifocal (67%) boost (p = 0.09). In the first analysis of its kind in the literature, we demonstrate that multifocal MRI-directed intraprostatic SBRT SIB yields no acute high-grade toxicity and is not associated with a higher risk of low-grade GU and GI toxicity relative to unifocal boost. Longer follow is necessary to determine risk of late toxicity and oncologic efficacy.

Does a Dominant Intraprostatic Lesion Boost Require Daily Adaptation when Treated with Stereotactic Online Adaptive MR-Guided Therapy?

Multiple trials have demonstrated a dose-response relationship for radiation therapy in the treatment of localized prostate cancer. Recent data has also demonstrated a benefit with whole gland stereotactic radiation therapy (SBRT) in conjunction with a simultaneous integrated boost to the dominant intraprostatic lesion (DIL). SBRT with a DIL boost can often increase dose to nearby organs at risk such as the rectum and online adaptive MR guided radiation therapy (MGgRT) may offer a dosimetric and toxicity benefit. A prospective database of MRgRT patients was queried for intact prostate cancer patients who received SBRT with a SIB to the DIL. The guideline for adaptation for coverage was to ensure the PTV-prostate coverage at 95% of prescribed dose was greater than 92% or by discretion of the treating physician. Adaptions for organs at risk were made to meet prescription constraints. The number of fractions requiring adaptation to meet organs at risk constraints and/or adequate coverage were reviewed. A total of 26 patients were treated with SBRT with a DIL boost using stereotactic online adaptive MRgRT from 2020 to 2022. 10 of 26 patients were treated for re-irradiation of intact prostate. Out of the 130 fractions delivered, 107 fractions required adaptation (82.3%). 59 fractions were adapted for urethra (45.2%), 48 fractions were adapted for bladder (36.9%), 36 fractions were adapted for rectum (27.7%), 23 fractions were adapted for bladder neck (17.7%), and 19 fractions were adapted for coverage (14.6%). For 53 fractions (40.8 %), adaptation was required for more than one organ at risk. A total of 82.3% of fractions required adaptation for patients treated with SBRT with a DIL boost using stereotactic online adaptive MRgRT. Adaptation occurred most frequently for urethral (45.2%), bladder (36.9%), and rectal constraints (27.7%). Further studies are needed to elucidate if daily adaptive online MRgRT translates to reduced patient toxicity and improved quality of life.

PSOR02 Presentation Time: 12:05 PM: Evaluating the Prognostic Significance of Artificial Intelligence-Delineated Dominant Intraprostatic Lesion and Prostate Volume Measurements for I-125 LDR Prostate Brachytherapy

PSOR02 Presentation Time: 12:05 PM: Evaluating the Prognostic Significance of Artificial Intelligence-Delineated Dominant Intraprostatic Lesion and Prostate Volume Measurements for I-125 LDR Prostate Brachytherapy

Dosimetric correlates of toxicities and quality of life following two-fraction stereotactic ablative radiotherapy (SABR) for prostate cancer

PurposeThere is no evidence-based data to guide dose constraints in two-fraction prostate stereotactic ablative radiotherapy (SABR). Using individual patient-data from two prospective trials, we aimed to correlate dosimetric parameters with toxicities and quality of life (QoL) outcomes. Materials and methodsWe included 60 patients who had two-fraction prostate SABR in the 2STAR (NCT02031328) and 2SMART (NCT03588819) trials. The prescribed dose was 26 Gy to the prostate+/–32 Gy boost to the dominant intraprostatic lesions. Toxicities and QoL data were prospectively collected using CTCAEv4 and EPIC-26 questionnaire. The outcomes evaluated were acute and late grade ≥ 2 toxicities, and late minimal clinical important changes (MCIC) in QoL domains. Dosimetric parameters for bladder, urethra, rectum, and penile bulb were evaluated. ResultsThe median follow-up was 56 months (range: 39–78 months). The cumulative incidence of grade ≥ 2 genitourinary (GU), gastrointestinal (GI), and sexual toxicities were 62%, 3%, and 17% respectively in the acute setting (<3 months), and 57%, 15%, and 52% respectively in late setting (>6 months). There were 36%, 28%, and 29% patients who had late MCIC in urinary, bowel and sexual QoL outcomes respectively. Bladder 0.5 cc was significant predictor for late grade ≥ 2 GU toxicities, with optimal cut-off of 25.5 Gy. Penile bulb D5cc was associated of late grade ≥ 2 sexual toxicities (no optimal cut-off was identified). No dosimetric parameters were identified to be associated with other outcomes. ConclusionUsing real-life patient data from prospective trials with medium-term follow-up, we identified additional dose constraints that may mitigate the risk of late treatment-related toxicities for two-fraction prostate SABR.

68Ga]Ga-PSMA and [68Ga]Ga-RM2 PET/MRI vs. Histopathological Images in Prostate Cancer: A New Workflow for Spatial Co-Registration.

This study proposed a new workflow for co-registering prostate PET images from a dual-tracer PET/MRI study with histopathological images of resected prostate specimens. The method aims to establish an accurate correspondence between PET/MRI findings and histology, facilitating a deeper understanding of PET tracer distribution and enabling advanced analyses like radiomics. To achieve this, images derived by three patients who underwent both [68Ga]Ga-PSMA and [68Ga]Ga-RM2 PET/MRI before radical prostatectomy were selected. After surgery, in the resected fresh specimens, fiducial markers visible on both histology and MR images were inserted. An ex vivo MRI of the prostate served as an intermediate step for co-registration between histological specimens and in vivo MRI examinations. The co-registration workflow involved five steps, ensuring alignment between histopathological images and PET/MRI data. The target registration error (TRE) was calculated to assess the precision of the co-registration. Furthermore, the DICE score was computed between the dominant intraprostatic tumor lesions delineated by the pathologist and the nuclear medicine physician. The TRE for the co-registration of histopathology and in vivo images was 1.59 mm, while the DICE score related to the site of increased intraprostatic uptake on [68Ga]Ga-PSMA and [68Ga]Ga-RM2 PET images was 0.54 and 0.75, respectively. This work shows an accurate co-registration method for histopathological and in vivo PET/MRI prostate examinations that allows the quantitative assessment of dual-tracer PET/MRI diagnostic accuracy at a millimetric scale. This approach may unveil radiotracer uptake mechanisms and identify new PET/MRI biomarkers, thus establishing the basis for precision medicine and future analyses, such as radiomics.

Assessing the Feasibility of Using Artificial Intelligence–Segmented Dominant Intraprostatic Lesion for Focal Intraprostatic Boost With External Beam Radiation Therapy

The delineation of dominant intraprostatic gross tumor volumes (GTVs) on multiparametric magnetic resonance imaging (mpMRI) can be subject to interobserver variability. We evaluated whether deep learning artificial intelligence (AI)-segmented GTVs can provide a similar degree of intraprostatic boosting with external beam radiation therapy (EBRT) as radiation oncologist (RO)-delineated GTVs. We identified 124 patients who underwent mpMRI followed by EBRT between 2010 and 2013. A reference GTV was delineated by an RO and approved by a board-certified radiologist. We trained an AI algorithm for GTV delineation on 89 patients, and tested the algorithm on 35 patients, each with at least 1 PI-RADS (Prostate Imaging Reporting and Data System) 4 or 5 lesion (46 total lesions). We then asked 5 additional ROs to independently delineate GTVs on the test set. We compared lesion detectability and geometric accuracy of the GTVs from AI and 5 ROs against the reference GTV. Then, we generated EBRT plans (77 Gy prostate) that boosted each observer-specific GTV to 95 Gy. We compared reference GTV dose (D98%) across observers using a mixed-effects model. On a lesion level, AI GTV exhibited a sensitivity of 82.6% and positive predictive value of 86.4%. Respective ranges among the 5 RO GTVs were 84.8% to 95.7% and 95.1% to 100.0%. Among 30 GTVs mutually identified by all observers, no significant differences in Dice coefficient were detected between AI and any of the 5 ROs. Across all patients, only 2 of 5 ROs had a reference GTV D98% that significantly differed from that of AI by 2.56 Gy (P=.02) and 3.20 Gy (P=.003). The presence of false-negative (-5.97 Gy; P < .001) but not false-positive (P=.24) lesions was associated with reference GTV D98%. AI-segmented GTVs demonstrate potential for intraprostatic boosting, although the degree of boosting may be adversely affected by false-negative lesions. Prospective review of AI-segmented GTVs remains essential.

Higher Preoperative Maximum Standardised Uptake Values (SUVmax) Are Associated with Higher Biochemical Recurrence Rates after Robot-Assisted Radical Prostatectomy for [68Ga]Ga-PSMA-11 and [18F]DCFPyL Positron Emission Tomography/Computed Tomography.

This study aimed to investigate the association between the 68Ga- or 18F-radiolabeled prostate-specific membrane antigen (PSMA) tracer expression, represented by the maximum standardised uptake value (SUVmax) of the dominant intraprostatic lesion, and biochemical recurrence (BCR) in primary prostate cancer (PCa) patients prior to robot-assisted radical prostatectomy (RARP). This was a retrospective, multi-centre cohort study of 446 patients who underwent [68Ga]Ga-PSMA-11 (n = 238) or [18F]DCFPyL (n = 206) Positron Emission Tomography/Computed Tomography (PET/CT) imaging prior to RARP. SUVmax was measured in the dominant intraprostatic PCa lesions. [18F]DCFPyL patients were scanned 60 ([18F]DCFPyL-60; n = 106) or 120 ([18F]DCFPyL-120; n = 120) minutes post-injection of a radiotracer and were analysed separately. To normalise the data, SUVmax was log transformed for further analyses. During a median follow-up of 24 months, 141 (30.4%) patients experienced BCR. Log2SUVmax was a significant predictor for BCR (p < 0.001). In the multivariable analysis accounting for these preoperative variables: initial prostate-specific antigen (PSA), radiologic tumour stage (mT), the biopsy International Society of Urological Pathology grade group (bISUP) and the prostate imaging and reporting data system (PI-RADS), Log2SUVmax was found to be an independent predictor for BCR in [68Ga]Ga-PSMA-11 (HR 1.32, p = 0.04) and [18F]DCFPyL-120 PET/CT scans (HR 1.55, p = 0.04), but not in [18F]DCFPyL-60 ones (HR 0.92, p = 0.72). The PSMA expression of the dominant intraprostatic lesion proved to be an independent predictor for BCR in patients with primary PCa who underwent [68Ga]Ga-PSMA-11 or [18F]DCFPyL-120 PET/CT scans, but not in those who underwent [18F]DCFPyL-60 PET/CT scans.

To Boost or Not to Boost: Pooled Analyses From 2-Fraction SABR Trials for Localized Prostate Cancer

Focal boost to dominant intraprostatic lesion (DIL) is an approach for dose escalation in prostate radiation therapy. In this study, we aimed to report the outcomes of 2-fraction SABR ± DIL boost. We included 60 patients with low- to intermediate-risk prostate cancer enrolled in 2 phase 2 trials (30 patients in each trial). In the 2STAR trial (NCT02031328), 26 Gy (equivalent dose in 2-Gy fractions=105.4 Gy) was delivered to the prostate. In the 2SMART trial (NCT03588819), 26 Gy was delivered to the prostate, with up to 32 Gy boost to magnetic resonance imaging-defined DIL (equivalent dose in 2-Gy fractions=156.4 Gy). The reported outcomes included prostate-specific antigen (PSA) response (ie, <0.4 ng/mL) at 4 years (4yrPSARR), biochemical failure (BF), acute and late toxicities, and quality of life (QOL). In 2SMART, median DIL D99% of 32.3 Gy was delivered. Median follow-up was 72.7 months (range, 69.1-75.) in 2STAR and 43.6 months (range, 38.7-49.5) in 2SMART. The 4yrPSARR was 57% (17/30) in 2STAR and 63% (15/24) in 2SMART (P=0.7). The 4-year cumulative BF was 0% in 2STAR and 8.3% in 2SMART (P=0.1). The 6-year BF in 2STAR was 3.5%. For genitourinary toxicities, there were differences in grade ≥1 urinary urgency in the acute (0% vs 47%; P < .001) and late settings (10% vs 67%; P < .001) favoring 2STAR. For urinary QOL, no difference was observed in the acute setting, but lower proportion in 2STAR had minimal clinically important changes in urinary QOL score in the late setting (21% vs 50%; P=.03). There were no significant differences in gastrointestinal and sexual toxicities and QOL in both acute and late settings between the 2 trials. This study presents the first prospective data comparing 2-fraction prostate SABR ± DIL boost. The addition of DIL boost resulted in similar medium-term efficacy (in 4yrPSARR and BF), with impact on late urinary QOL outcomes.

Prostate cancer detection and segmentation on MRI using non-local mask R-CNN with histopathological ground truth.

Automatic detection and segmentation of intraprostatic lesions (ILs) on preoperative multiparametric-magnetic resonance images (mp-MRI) can improve clinical workflow efficiency and enhance the diagnostic accuracy of prostate cancer and is an essential step in dominant intraprostatic lesion boost. The goal is to improve the detection and segmentation accuracy of 3D ILs in MRI by a proposed a deep learning (DL)-based algorithm with histopathological ground truth. This retrospective study included 262 patients with in vivo prostate biparametric MRI (bp-MRI) scans and were divided into three cohorts based on their data analysis and annotation. Histopathological ground truth was established by using histopathology images as delineation reference standard on cohort 1, which consisted of 64 patients and was randomly split into 20 training, 12 validation, and 32 testing patients. Cohort 2 consisted of 158 patients with bp-MRI based lesion delineation, and was randomly split into 104 training, 15 validation, and 39 testing patients. Cohort 3 consisted of 40 unannotated patients, used in semi-supervised learning. We proposed a non-local Mask R-CNN and boosted its performance by applying different training techniques. The performance of non-local Mask R-CNN was compared with baseline Mask R-CNN, 3D U-Net and an experienced radiologist's delineation and was evaluated by detection rate, dice similarity coefficient (DSC), sensitivity, and Hausdorff Distance (HD). The independent testing set consists of 32 patients with histopathological ground truth. With the training technique maximizing detection rate, the non-local Mask R-CNN achieved 80.5% and 94.7% detection rate; 0.548 and 0.604 DSC; 5.72 and 6.36 95 HD (mm); 0.613 and 0.580 sensitivity for ILs of all Gleason Grade groups (GGGs) and clinically significant ILs (GGG>2), which outperformed baseline Mask R-CNN and 3D U-Net. For clinically significant ILs, the model segmentation accuracy was significantly higher than that of the experienced radiologist involved in the study, who achieved 0.512 DSC (p=0.04), 8.21 (p=0.041) 95 HD (mm), and 0.398 (p=0.001) sensitivity. The proposed DL model achieved state-of-art performance and has the potential to help improve radiotherapy treatment planning and noninvasive prostate cancer diagnosis.