Enhancing Androgen Deprivation Therapy (ADT) integration in prostate cancer: Insights for Stereotactic Body Radiotherapy (SBRT) and brachytherapy modalities.

The utilization of Androgen Deprivation Therapy (ADT) in conjunction with Stereotactic Body Radiotherapy (SBRT) and Brachytherapy (BT) boost in prostate cancer treatment is a subject of ongoing debate and evolving clinical practice. While contemporary trends lean towards underutilizing ADT with these modalities, existing evidence suggests that its omission may lead to potentially inferior oncologic outcomes. Recommendations for ADT use should be patient-centric, considering individual risk profiles and comorbidities, with a focus on achieving optimal oncologic outcomes while minimizing potential side effects. Ongoing clinical trials, such as PACE-C, SPA, SHIP 0804, and SHIP 36B, are anticipated to provide valuable insights into the optimal use and duration of ADT in both SBRT and BT settings. Until new evidence emerges, it is recommended to initiate ADT for unfavorable intermediate-risk and high-risk prostate cancer patients undergoing radiotherapy, with a minimum duration of 6 months for unfavorable intermediate-risk patients and at least 12 months for those with high-risk characteristics. The decision to incorporate ADT into these radiation therapy modalities should be individualized, acknowledging the unique needs of each patient and emphasizing a tailored approach to achieve the best possible oncologic outcomes.

Prospective study of HDR brachytherapy (BT), external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT): 10-years experience of an MRI-guided approach.

OBJECTIVES: To evaluate the predictive factors for biochemical failure and distant metastases in a prospective cohort of patients with localized prostate cancer treated with the combination of HDR BT and EBRT. METHODS AND MATERIALS: Patients with intermediate (IR) or high-risk (HR) prostate adenocarcinoma received a single fraction of HDR of 15 Gy combined with RT of 37.5 Gy in 15 fractions. ADT duration was used depending on risk-group. Descriptive analyses were performed. Univariate and multivariate Hazard Ratios were obtained. Finally, the Kaplan-Meier model was used to describe the survival of the events of interest. RESULTS: 309 patients were treated prospectively (199 were IR and 110 HR). Median age was 72 years; 58.3 % were MRI stage ≤ T2c, 34.1 % T3a and 7.6 % T3b; ISUP-grade 1-3 in 78.9 % and ISUP 4-5 in 21.1 %. 71.8 % of patients had ≤ 50 % positive-cores in biopsy and 28.2 % had > 50 %. Median pre-treatment PSA was 9.9 ng/mL. After a median follow-up of 88 months, 41 patients presented biochemical failure and 18 developed distant metastases. Multivariate cox-regression analyses found that MR-T3b Stage (HR 3.88, p = 0.001) and ADT use (HR 3.99, p = 0.03) were the only predictive factors for biochemical failure and the number of positive cores (>50 %) the only independent predictive factor of distant metastases (HR 4.36, p = 0.002). CONCLUSIONS: Patients with mpMRI evidence of invasion of the SV and involvement of more than 50% of the cores in the prostate biopsy are patients with a higher risk of presenting a biochemical recurrence or developing metastasis due to their prostate cancer, respectively.

MRI detected extaprostatic extension (EPE) in prostate cancer: Do all T3a patients have the same outcomes?

MRI-detected T3a prostate cancer is a heterogeneous disease. This post-hoc analysis of a prospective trial found that patients with T3a disease presenting obliteration of the recto-prostatic angle, contact-asymmetry of neuro-vascular bundle and periprostatic fat invasion, may be at higher risk of biochemical failure and metastases.

Impact of rectum and bladder anatomy in intrafractional prostate motion during hypofractionated radiation therapy.

BACKGROUND: The objective was to determine the magnitude of the prostate intrafractional motion relative to bony pelvis anatomy, and to evaluate the relationship between this displacement and some clinical and anatomical variables. MATERIALS AND METHODS: The prospective study consisted of 544 images (375 pre-treatment CBCT and 169 post-treatment CBCT) from 15 prostate adenocarcinoma patients that were used for intrafractional prostate motion determination. In addition, two radiation oncologists re-contoured the bladder and rectum on each CBCT according to the patient's anatomy of the day. ANOVA and correlation analysis followed by linear regression analysis were performed to identify clinical or anatomical variables that predict large prostate intrafractional motion. RESULTS: Prostate shift increased in patients with hormone therapy (p ≤ 0.02). The regression analysis showed that patients with large bladder intrafractional filling (p < 0.01) and a large bladder volume difference from planning CT were more likely to experience bigger longitudinal prostate motion (> 3 mm). Recommended bladder size values: anterior-posterior size ≤ 10 cm and anterior-posterior/cranio-caudal ratio ≤ 1.7, both parameters measured in the midsagittal prostate plane, were defined. CONCLUSIONS: The treatment margin should not be reduced for those patients who were treated with hormone therapy and/or whose rectum or bladder was far from complying the preparation protocol conditions.

Reduced late urinary toxicity with high-dose intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer.

BACKGROUND/PURPOSE: To evaluate the impact of intensity-modulated radiotherapy (IMRT) with intra-prostate fiducial markers image-guided radiotherapy (IGRT) on the incidence of late urinary toxicity compared to 3D conformal radiotherapy (3DCRT) for patients with prostate cancer (PC). METHODS AND MATERIALS: We selected 733 consecutive patients with localized PC treated with dose-escalation radiotherapy between 2001 and 2014. Eligibility criteria were radiation dose >72.0 Gy, no pelvic RT and minimum follow-up 24 months. 438 patients were treated with 3DCRT and 295 with IMRT. Acute and late urinary complications were assessed using the EORTC/RTOG and CTCAEs v3.0 definition. The Cox regression model was used to compare grade ≥2 urinary toxicity between both techniques. The median follow-up was 75 months (range 24-204). RESULTS: The median isocenter radiation dose was 78.7 Gy for 3DCRT and 80.7 Gy for IMRT/IGRT (p < 0.001). The 5-year incidence of late grade ≥2 urinary toxicity was 6.4% for IMRT and 10.8% for 3DCRT [hazard ratio (HR) 0.575, p = 0.056]. The corresponding 5-year estimates of late grade ≥2 hematuria were 2% for IMRT and 5.3% for 3DCRT (HR 0.296, p = 0.024). On multivariate analysis, the antecedent of prior transurethral resection of the prostate was also a strong predictor of a higher risk of urinary complications (HR 2.464, p = 0.002) and of hematuria (HR 5.196, p < 0.001). CONCLUSION: Compared with 3DCRT, high-dose IMRT/IGRT is associated with a lower rate of late urinary complications in spite of higher radiation dose.