Ultrahypofractionated Radiotherapy versus Conventional to Moderate Hypofractionated Radiotherapy for Clinically Localized Prostate Cancer

The purpose of this study was to compare the toxicity (first endpoint) and efficacy (second endpoint) of ultrahypofractionated radiotherapy (UHF) and dose-escalated conventional to moderate hypofractionated radiotherapy (DeRT) for clinically localized prostate cancer. We compared 253 patients treated with UHF and 499 patients treated with DeRT using multi-institutional retrospective data. To analyze toxicity, we divided UHF into High-dose UHF (H-UHF; equivalent doses of 2 Gy per fraction: EQD2 > 100 Gy1.5) and low-dose UHF (L-UHF; EQD2 ≤ 100 Gy1.5). In toxicity, H-UHF elevated for 3 years accumulated late gastrointestinal and genitourinary toxicity grade ≥ 2 (11.1% and 9.3%) more than L-UHF (3% and 1.2%) and DeRT (3.1% and 4.8%, p = 0.00126 and p = 0.00549). With median follow-up periods of 32.0 and 61.7 months, the actuarial 3-year biochemical failure-free survival rates were 100% (100% and 100% in the L-UHF and H-UHF) and 96.3% in the low-risk group, 96.5% (97.1% and 95.6%) and 94.9% in the intermediate-risk group, and 93.7% (100% and 94.6%) and 91.7% in the high-risk group in the UHF and DeRT groups, respectively. UHF showed equivocal efficacy, although not conclusive but suggestive due to a short follow-up period of UHF. L-UHF using EQD2 ≤ 100 Gy1.5 is a feasible UHF schedule with a good balance between toxicity and efficacy.

Evaluation of Safety for Scanning Carbon-Ion Radiotherapy in Hemodialysis Patients with Prostate Cancer

Background/Aim The efficacy and safety of carbon-ion radiotherapy (CIRT) for prostate cancer have already been demonstrated. The number of hemodialysis (HD) patients is increasing. Although the toxicity of CIRT in HD patients may be more severe, it has been insufficiently investigated. Therefore, we retrospectively analyzed the safety of CIRT for HD patients with prostate cancer in the present study. Materials and Methods Five HD patients with prostate cancer who underwent CIRT at the Kanagawa Cancer Center during November 2015–2020 were included in this study. CIRT was delivered by the raster scanning method (sCIRT). Adverse events were assessed using the CTCAE v5.0. The dose-volume histogram (DVH) parameters of the target volume and normal organs were evaluated between initial planning computed tomography (CT) and in-room CT images. Results In the acute phase, Grade 1 genitourinary toxicity was recorded in 1 patient. In the late phase, Grade 1 genitourinary toxicity was recorded in 2 patients. No gastrointestinal toxicities were noted during the follow-up period. In-room CT analysis revealed no significant differences among all DVH parameters of the target volume and normal organs when compared with the treatment plan dose. Conclusions The safety of sCIRT for prostate cancer in HD patients was investigated in the present study. In-room CT analysis suggested the robustness of the treatment plan. According to the present results, sCIRT for prostate cancer can be safely performed in HD patients.

Gastrointestinal and genitourinary toxicity profiles of metformin versus placebo in men with prostate cancer receiving prostate radiotherapy: interim toxicity results of a double-blinded, multicenter, phase II randomized controlled trial

Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18–36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.

Evaluation of T2-Weighted MRI for Visualization and Sparing of Urethra with MR-Guided Radiation Therapy (MRgRT) On-Board MRI

Purpose: To evaluate urethral contours from two optimized urethral MRI sequences with an MR-guided radiotherapy system (MRgRT). Methods: Eleven prostate cancer patients were scanned on a MRgRT system using optimized urethral 3D HASTE and 3D TSE. A resident radiation oncologist contoured the prostatic urethra on the patients’ planning CT, diagnostic 3T T2w MRI, and both urethral MRIs. An attending radiation oncologist reviewed/edited the resident’s contours and additionally contoured the prostatic urethra on the clinical planning MRgRT MRI (bSSFP). For each image, the resident radiation oncologist, attending radiation oncologist, and a senior medical physicist qualitatively scored the prostatic urethra visibility. Using MRgRT 3D HASTE-based contouring workflow as baseline, prostatic urethra contours drawn on CT, diagnostic MRI, clinical bSSFP and 3D TSE were evaluated relative to the contour on 3D HASTE using 95th percentile Hausdorff distance (HD95), mean-distance-to-agreement (MDA), and DICE coefficient. Additionally, prostatic urethra contrast-to-noise-ratios (CNR) were calculated for all images. Results: For two out of three observers, the urethra visibility score for 3D HASTE was significantly higher than CT, and clinical bSSFP, but was not significantly different from diagnostic MRI. The mean HD95/MDA/DICE values were 11.35 ± 3.55 mm/5.77 ± 2.69 mm/0.07 ± 0.08 for CT, 7.62 ± 2.75 mm/3.83 ± 1.47 mm/0.12 ± 0.10 for CT + diagnostic MRI, 5.49 ± 2.32 mm/2.18 ± 1.19 mm/0.35 ± 0.19 for 3D TSE, and 6.34 ± 2.89 mm/2.65 ± 1.31 mm/0.21 ± 0.12 for clinical bSSFP. The CNR for 3D HASTE was significantly higher than CT, diagnostic MRI, and clinical bSSFP, but was not significantly different from 3D TSE. Conclusion: The urethra’s visibility scores showed optimized urethral MRgRT 3D HASTE was superior to the other tested methodologies. The prostatic urethra contours demonstrated significant variability from different imaging and workflows. Urethra contouring uncertainty introduced by cross-modality registration and sub-optimal imaging contrast may lead to significant treatment degradation when urethral sparing is implemented to minimize genitourinary toxicity.

68Ga-PSMA-PET screening and transponder-guided salvage radiotherapy to the prostate bed alone for biochemical recurrence following prostatectomy: interim outcomes of a phase II trial

Purpose To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET). Methods This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1–2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL). Results Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12–0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3–58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable. Conclusion Pre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL. Trial registration number ACTRN12615001183572, 03/11/2015, retrospectively registered.

High-dose-rate brachytherapy with external beam radiotherapy versus low-dose-rate brachytherapy with or without external beam radiotherapy for clinically localized prostate cancer

To compare the outcomes of localized prostate cancer treatment with high-dose-rate brachytherapy (HDR-BT) and low-dose-rate brachytherapy (LDR-BT), we examined 924 patients treated with HDR-BT + external beam radiotherapy (EBRT) and 500 patients treated with LDR-BT ± EBRT using multi-institutional retrospective data. The HDR-BT treated advanced disease with more hormonal therapy than LDR-BT. To reduce background selection bias, we performed inverse probability of treatment weighting (IPTW) analysis using propensity scores and excluded patients with T3b-4 disease/ initial prostate-specific antigen (PSA) levels > 50 ng/ml. The actuarial 5-year biochemical control rates (5y-bNED) were 96.3% and 95.7% in the HDR-BT and LDR-BT groups, respectively. The corresponding values were 100% and 96.5% in the low-risk group; 97.4% and 97.1% in the intermediate-risk group (97.2% and 97% in the higher titer group and 97.5% and 94.6% in the lower titer group, respectively); and 95.7% and 94.9% in the selected high-risk group, respectively. IPTW correction indicated no significant difference among the groups. The 5y-bNED in the HDR-BT + EBRT, LDR-BT + EBRT, and LDR-BT alone groups were 96.3%, 95.5%, and 97%, respectively (P = 0.3011). The corresponding values were 97.4%, 94.7%, and 96.6% (P = 0.1004) in the intermediate-risk group (97.5%, 100%, and 94.5% in the lower titer group [P = 0.122] and 97.2%, 96.2%, and 100% [P = 0.664] in the higher titer group, respectively) and 95.7%, 95.5%, and 100% (P = 0.859) in the high-risk group, respectively. The HDR-BT group showed a lower incidence of acute grade ≥ 2 genitourinary toxicities; the incidence of other early and late grade ≥ 2 toxicities were similar between the HDR-BT and LDR-BT groups. Acute genitourinary toxicity predicted the occurrence of late genitourinary toxicity. EBRT increased the risk of grade ≥ 2 gastrointestinal toxicity. HDR-BT + EBRT is a good alternative to LDR-BT ± EBRT for low-, intermediate-, and selected high-risk patients.