Five-year outcomes of fractionated stereotactic body radiotherapy for oligometastatic prostate cancer from the TRANSFORM phase II trial.

Metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5-year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT-based MDT. The primary endpoint was 5-year treatment escalation-free survival (TE-FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone-naïve at baseline. The rate of 5-year TE-FS was 21.7% (95% confidence interval [CI]: 15.7%-28.7%) overall and 25.4% (95% CI: 18.1%-33.9%) in the hormone-naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4-5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05-2.01, p = .026), a higher baseline prostate-specific antigen (PSA) (HR = 1.06, 95% CI: 1.03-1.09, p < .001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40-3.26, p < .001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow-up, 18.9% (95% CI: 13.2%-25.7%) of participants were free from treatment escalation (median follow-up of 67.9 months) and two participants had an undetectable PSA level. No treatment-related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT-based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT-based MDT to standard-of-care ADT-based approaches are required to evaluate the impact of delaying ADT on survival.

Dose-escalated radiotherapy to 82 Gy for prostate cancer following insertion of a peri-rectal hydrogel spacer: 3-year outcomes from a phase II trial.

BACKGROUND: Dose-escalation to above 80 Gy during external beam radiotherapy for localised prostate cancer leads to improved oncological outcomes but also substantially increased rectal toxicity. The aim of this study was to demonstrate the safety and efficacy of escalating the dose to 82 Gy following insertion of a peri-rectal hydrogel spacer (HS) prior to radiotherapy. METHODS: This was a single arm, open-label, prospective study of men with localised prostate cancer who were prescribed a course of intensity modulated radiotherapy escalated to 82 Gy in 2 Gy fractions following insertion of the SpaceOAR™ HS (Boston Scientific, Marlborough, MA). Patients were prescribed a standard course of 78 Gy in 2 Gy fractions where rectal dose constraints could not be met for the 82 Gy plan. The co-primary endpoints were the rate of grade 3 gastrointestinal (GI) and genitourinary (GU) adverse events (CTCAE, v4), and patient-reported quality of life (QoL) (EORTC QLQ-C30 and PR25 modules), up to 37.5 months post-treatment. RESULTS: Seventy patients received treatment on the study, with 64 (91.4%) receiving an 82 Gy treatment course. The median follow-up time post-treatment was 37.4 months. The rate of radiotherapy-related grade 3 GI and GU adverse events was 0% and 2.9%, respectively. There were 2 (2.9%) grade 3 adverse events related to insertion of the HS. Only small and transient declines in QoL were observed; there was no clinically or statistically significant decline in QoL beyond 13.5 months and up to 37.5 months post-treatment, compared to baseline. No late RTOG-defined grade ≥ 2 GI toxicity was observed, with no GI toxicity observed in any patient at 37.5 months post-treatment. Nine (12.9%) patients met criteria for biochemical failure within the follow-up period. CONCLUSIONS: Dose-escalation to 82 Gy, facilitated by use of a hydrogel spacer, is safe and feasible, with minimal toxicity up to 37.5 months post-treatment when compared to rates of rectal toxicity in previous dose-escalation trials up to 80 Gy. Trials with longer follow-up of oncological and functional outcomes are required to robustly demonstrate a sustained widening of the therapeutic window. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12621000056897 , 22/01/2021. Retrospectively registered.

Focal low dose-rate brachytherapy for low to intermediate risk prostate cancer: preliminary experience at an Australian institution.

BACKGROUND: Focal treatment for prostate cancer (PCa) is a hybrid approach combining ablative treatment of the involved prostate gland and continued active surveillance (AS) of the unaffected gland. Low dose-rate (LDR) brachytherapy can be used as a lesion-targeted focal therapy, however, further studies are required to support its use. The aim of this study is to evaluate the dosimetry, toxicity and oncological outcomes of men receiving lesion-targeted focal LDR brachytherapy for low to intermediate risk PCa. METHODS: This is a retrospective cohort study of 26 men with unifocal, low to intermediate grade PCa diagnosed on a combination of multiparametric-magnetic resonance imaging (mp-MRI) and targeted plus template transperineal (TP) biopsy, who received focal LDR brachytherapy at a single institution. Brachytherapy involved a single monotherapy implant using iodine-125 seeds to deliver a prescribed dose of 145 Gy to the index lesion. RESULTS: The mean focal planning target volume (F-PTV) as a percentage of the prostate volume was 24.5%. The percentage of the focal gross tumour volume (F-GTV) receiving 100% of the prescription dose was 100% for 12 patients and ≥98% for 18 patients. The median follow-up for toxicity and biochemical control outcomes was 23.1 [interquartile range (IQR) 19.1-31.3] and 24.2 (IQR 17.9-30.0) months, respectively. Grade 2 urinary and erectile toxicities were reported by 29.2% and 45.8% of patients, respectively, with resolution of urinary symptoms to baseline by last follow-up. There were no grade ≥3 urinary or erectile toxicities or grade ≥2 rectal toxicity. All 21 patients who underwent a repeat mp-MRI and TP biopsy at 12-24 months post-treatment were negative for clinically significant disease and 25 (96.2%) patients were free from biochemical failure (FFBF). CONCLUSIONS: Focal LDR brachytherapy is associated with a favourable toxicity profile and a high rate of control of significant PCa at 12-18 months post-treatment. We have commenced the LIBERATE prospective registry in focal LDR brachytherapy based on the highly encouraging outcomes of this initial experience.

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.

Fractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: Interim outcomes of a prospective clinical trial.

Stereotactic body radiotherapy (SBRT) can delay escalation to systemic treatment in men with oligometastatic prostate cancer (PCa). However, large, prospective studies are still required to evaluate the efficacy of this approach in different patient groups. This is the interim analysis of a prospective, single institution study of men relapsing with up to five synchronous lesions following definitive local treatment for primary PCa. Our aim was to determine the proportion of patients not requiring treatment escalation following SBRT. In total, 199 patients were enrolled to receive fractionated SBRT (50 Gray in 10 fractions) to each visible lesion. Fourteen patients were castration resistant at enrolment. The proportion of patients not requiring treatment escalation 2 years following SBRT was 51.7% (95% CI: 44.1-59.3%). The median length of treatment escalation-free survival over the entire follow-up period was 27.1 months (95% CI; 21.8-29.4 months). Prior androgen deprivation therapy (ADT) predicted a significantly lower rate of freedom from treatment escalation at 2 years compared to no prior ADT (odds ratio = 0.21, 95% CI: 0.08-0.54, p = 0.001). There was no difference in the efficacy of SBRT when treating 4-5 vs. 1-3 initial lesions. A prostate-specific antigen (PSA) decline was induced in 75% of patients, with PSA readings falling to an undetectable level in six patients. No late grade three toxicities were observed. These interim results suggest that SBRT can be used to treat up to five synchronous PCa oligometastases to delay treatment escalation.

Dose reduction to organs at risk with deep-inspiration breath-hold during right breast radiotherapy: a treatment planning study.

BACKGROUND: The addition of regional nodal radiation (RNI) to whole breast irradiation for high risk breast cancer improves metastases free survival and new data suggests it contributes additional benefit to overall survival. Deep inspiration breath hold (DIBH) has been shown to reduce cardiac and pulmonary dose in the context of left-sided disease treated with or without RNI, yet few studies have investigated its utility for right-breast cancer. This study investigates the potential advantages of DIBH in local and locoregional radiotherapy for right-sided breast cancer. METHODS: Free-breathing (FB) and DIBH computed tomography datasets were obtained from twenty patients who previously underwent radiotherapy for left-sided breast cancer. Ten patients were retrospectively planned for whole right breast only irradiation and ten patients were planned for irradiation to the whole breast plus ipsilateral supra-clavicular (SC) nodes, with and without irradiation of the ipsilateral internal mammary nodes (IMN). Dose-volume metrics for the clinical target volume, lungs, heart, left anterior descending artery, right coronary artery (RCA) and liver were recorded. Differences between FB and DIBH plans were analysed using Wilcoxon signed-rank tests, with P < 0.05 considered statistically significant. RESULTS: DIBH increased the average total lung volume compared to FB in both breast only and breast plus RNI cohorts (P = 0.001). For the breast only group, there was no significant improvement in any ipsilateral lung dose-volume metric between FB and DIBH. However, for the breast plus RNI group, there was an improvement in ipsilateral lung mean dose (18.9 ± 3.2 Gy to 15.9 ± 2.3 Gy, P = 0.002) and V20Gy (45.3 ± 13.3% to 32.9 ± 9.4%, P = 0.002). In addition, DIBH significantly reduced the maximum dose to the RCA for RNI (11.6 ± 7.2 Gy to 5.6 ± 2.9 Gy, P = 0.03). Significant reductions in the liver V20Gy and maximum dose were observed in all cohorts during DIBH compared to FB. CONCLUSIONS: DIBH is a promising approach for right-breast radiotherapy with considerable sparing of normal tissue, particularly when the ipsilateral IMNs are also irradiated.

Stereotactic radiosurgery for brain and spine metastases.

Metastases to the brain and spine are common and difficult to treat. Stereotactic radiosurgery (SRS) is a non-invasive treatment option for some individuals, and may obviate the need for open surgery and/or whole brain radiotherapy. Over the past decade there has been an increased number of patients undergoing SRS for the treatment of metastatic disease, and multiple published studies show favourable results in terms of local disease control. We review the available literature pertaining to the application of SRS for the treatment of brain and spine metastases, together with its limitations and outcomes.