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Ablative Radiotherapy in Prostate Cancer: Stereotactic Body Radiotherapy and High Dose Rate Brachytherapy.

ABSTRACT: Prostate cancer (PCa) is the most common noncutaneous solid organ malignancy among men worldwide. Radiation therapy is a standard of care treatment option that has historically been delivered in the form of small daily doses of radiation over the span of multiple weeks. PCa appears to have a unique sensitivity to higher doses of radiation per fraction, rendering it susceptible to abbreviated forms of treatment. Stereotactic body radiation therapy (SBRT) and high-dose-rate brachytherapy (HDRBT) are both modern radiation modalities that allow the precise delivery of ablative doses of radiation to the prostate while maximally sparing sensitive surrounding normal structures. In this review, we highlight the evidence regarding the radiobiology, oncological outcomes, toxicity and dose/fractionation schemes of SBRT and HDRBT monotherapy in men with low-and intermediate-risk PCa.

SUBMITTER: Ma TM

PROVIDER: S-EPMC7761604 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Ablative Radiotherapy in Prostate Cancer: Stereotactic Body Radiotherapy and High Dose Rate Brachytherapy.

Ma Ting Martin TM Lilleby Oscar O Lilleby Wolfgang A WA Kishan Amar U AU

Cancers 20201202 12

Prostate cancer (PCa) is the most common noncutaneous solid organ malignancy among men worldwide. Radiation therapy is a standard of care treatment option that has historically been delivered in the form of small daily doses of radiation over the span of multiple weeks. PCa appears to have a unique sensitivity to higher doses of radiation per fraction, rendering it susceptible to abbreviated forms of treatment. Stereotactic body radiation therapy (SBRT) and high-dose-rate brachytherapy (HDRBT) a ...[more]

PMID: 33276562

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Project description:Prostate is the most common non-cutaneous cancer diagnosed among men in North America. Fortunately most prostate cancers are screen detected and non-metastatic on diagnosis. Treatment options for men with localized prostate cancer include surgery ± postoperative radiation or radiation ± androgen deprivation therapy (ADT). Brachytherapy ± external beam radiation treatment (EBRT) appears to have superior long-term disease control over EBRT alone likely because of higher biologic effective dose delivered. Stereotactic ablative body radiation (SABR) is a novel, non-invasive, high-precision EBRT technique that allows safe delivery of biologic doses similar to brachytherapy with similar or lower side effects [measured using toxicity or quality of life (QOL) scales]. Efficacy for SABR appears to be similar to brachytherapy including positive biopsy rates 2-3 years post treatment, biochemical failure (BF) rates out to 10-year and incidence of metastases. SABR dose escalation reduces biopsy positivity and prostate-specific antigen (PSA) nadirs but increases genitourinary (GU) and gastrointestinal (GI) toxicity-no effect on BF has been realized yet. The overall treatment time (OTT) varies in many protocols. Phase 2 randomized data shows that QOL is better in the acute setting with a weekly course of treatment compared to an every other day treatment regimen with no difference in late setting. Follow-up data are immature and likely underpowered to determine efficacy differences. SABR is cheaper and uses less resource than any other radiation technique. Given the healthcare resource challenges (including financial resources), SABR would be a welcomed addition if studies show non-inferiority to other radiation techniques. For patients with de novo or metastatic disease on relapse, there is much enthusiasm regarding the use of SABR in the setting of oligometastatic prostate cancer. SABR appears to be feasible to deliver, well tolerated and may delay the next line of therapy. However, until adequately powered randomized studies confirm a benefit, such an approach cannot be considered standard of care treatment at this time. Enrollment of eligible prostate cancer patients onto SABR clinical trials should be encouraged.

Project description: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.

Project description:BackgroundUp to half of patients with localized prostate cancer experience biochemical relapse within 10 years after definitive radiotherapy. The aim of this prospective study was to investigate the toxicity, dose to the organs at risk (OARs), and efficacy of dose-intensified focal salvage radiotherapy.Methods and materialThirty-three patients (median age 68.8 years) with histologically confirmed relapse after primary definitive radiotherapy were enrolled between 2012 and 2019. No patients had metastases at imaging or in bone marrow aspiration. Twenty-three patients were treated with high dose-rate brachytherapy to the recurrent tumor, defined at multiparametric MRI, with 3 fractions of 10 Gy with two weeks interval, and 10 patients by stereotactic body radiotherapy with 35 Gy to the local recurrence and 25 Gy to the whole prostate in 5 fractions. We used the RTOG-scoring system to grade genitourinary (GU) and gastrointestinal toxicity (GI) at three months (acute), and at 12, 24, and 36 months (late). Dose-volume histogram parameters to the local recurrence and the OARs were obtained and 2 Gy equivalent (EQD2) total dose was calculated using the linear-quadratic model with α/β = 3 Gy. Efficacy was assessed by the progression-free interval and overall survival.ResultsMedian follow-up time was 81 months (range 21-115). The cumulative moderate to severe GI and GU toxicities were 3.0% (1/33) and 15.2% (5/33). Six patients had grade 1 acute GI toxicity, none had grade 2 or 3. One patient had grade 3 acute GU toxicity, two had grade 2, and fourteen had grade 1. One patient had late GI toxicity grade 2 and eight had grade 1. Four patients had late GU toxicity grade 2 and eight had grade 1. No patients had grade 3 late toxicity. The mean total D90 to the recurrent tumor was 77.7 ± 17.0 Gy. The mean total rectum D2cc was 17.0 ± 7.9 Gy and the mean total urethra D0.1cc was 29.1 ± 8.2 Gy. Twenty-eight patients had re-irradiation without androgen deprivation therapy (ADT). Nine of these are still relapse-free and 10 had a recurrence-free interval longer than 2 years.ConclusionThe toxicity of salvage radiotherapy was mild to moderate. One-third of the patients achieved long-term stable disease without ADT and one-third had a recurrence-free interval longer than 2 years. Some patients progressed rapidly and probably did not benefit from re-irradiation.

Project description:BackgroundTo evaluate acute and late genitourinary and gastrointestinal toxicities and patient reported urinary and sexual function following accelerated, hypofractionated external beam radiotherapy to the prostate, seminal vesicles and pelvic lymph nodes and high dose rate (HDR) brachytherapy or stereotactic body radiation therapy (SBRT) prostate boost.MethodsPatients at a single institution with NCCN intermediate- and high-risk localized prostate cancer with logistical barriers to completing five weeks of whole pelvic radiotherapy (WPRT) were retrospectively reviewed for toxicity following accelerated, hypofractionated WPRT (41.25 Gy in 15 fractions of 2.75 Gy). Patients also received prostate boost radiotherapy with either HDR brachytherapy (1 fraction of 15 Gy) or SBRT (19 Gy in 2 fractions of 9.5 Gy). The duration of androgen deprivation therapy was at the discretion of the treating radiation oncologist. Toxicity was evaluated by NCI CTCAE v 5.0.ResultsBetween 2015 and 2017, 22 patients with a median age of 71 years completed accelerated, hypofractionated WPRT. Median follow-up from the end of radiotherapy was 32 months (range 2-57). 5%, 73%, and 23% of patients had clinical T1, T2, and T3 disease, respectively. 86% of tumors were Gleason grade 7 and 14% were Gleason grade 9. 68% and 32% of patients had NCCN intermediate- and high-risk disease, respectively. 91% and 9% of patients received HDR brachytherapy and SBRT prostate boost following WPRT, respectively. Crude rates of grade 2 or higher GI and GU toxicities were 23% and 23%, respectively. 3 patients (14%) had late or persistent grade 2 toxicities of urinary frequency and 1 patient (5%) had late or persistent GI toxicity of diarrhea. No patient experienced grade 3 or higher toxicity at any time. No difference in patient-reported urinary or sexual function was noted at 12 months.ConclusionsAccelerated, hypofractionated whole pelvis radiotherapy was associated with acceptable GU and GI toxicities and should be further validated for those at risk for harboring occult nodal disease.

Dataset Information

Ablative Radiotherapy in Prostate Cancer: Stereotactic Body Radiotherapy and High Dose Rate Brachytherapy.

Publications

Ablative Radiotherapy in Prostate Cancer: Stereotactic Body Radiotherapy and High Dose Rate Brachytherapy.

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