Dataset Information

Robotic stereotactic body radiotherapy for localized prostate cancer: final analysis of the German HYPOSTAT trial.

ABSTRACT:

Purpose

We report results of the first German prospective multicenter single-arm phase II trial (ARO 2013-06; NCT02635256) of hypofractionated robotic stereotactic body radiotherapy (SBRT) for patients with localized prostate cancer (HYPOSTAT).

Methods

Patients eligible for the HYPOSTAT study had localized prostate cancer (cT1‑3 cN0 cM0), Gleason score ≤ 7, prostate-specific antigen (PSA) ≤ 15 ng/ml, prostate volume ≤ 80 cm³, and an International Prostate Symptom Score (IPSS) ≤ 12. Initially, inclusion was limited to patients ≥ 75 years or patients 70-74 years with additional risk factors. The trial protocol was later amended to allow for enrolment of patients aged ≥ 60 years. The treatment consisted of 35 Gy delivered in 5 fractions to the prostate and for intermediate- or high-risk patients, also to the proximal seminal vesicles using the CyberKnife system (Accuray Inc., Sunnyvale, CA, USA). Primary endpoint was the rate of treatment-related gastrointestinal or genitourinary grade ≥ 2 toxicity based on the RTOG scale 12-15 months after treatment. Secondary endpoints were acute toxicity, late toxicity, urinary function, quality of life, and PSA response.

Results

From July 2016 through December 2018, 85 eligible patients were enrolled and received treatment, of whom 83 could be evaluated regarding the primary endpoint. Patients mostly had intermediate-risk disease with a median PSA value of 7.97 ng/ml and Gleason score of 7a and 7b in 43.5% and 25.9% of patients, respectively. At the final follow-up 12-15 months after treatment, no patient suffered from treatment-related gastrointestinal or genitourinary grade ≥ 2 toxicity. Acute toxicity was mostly mild, with three grade 3 events, and the cumulative rate of grade ≥ 2 genitourinary toxicity was 8.4% (95% CI 4.1-16.4%). There were no major changes in urinary function or quality of life. The median PSA value dropped to 1.18 ng/ml 12-15 months after treatment. There was one patient who developed distant metastases.

Conclusion

Robotic SBRT with 35 Gy in 5 fractions was associated with a favorable short-term toxicity profile. Recruitment for the HYPOSTAT‑2 trial (ARO-2018‑4; NCT03795337), which further analyses the late toxicity of this regimen with a planned sample size of 500 patients, is ongoing.

SUBMITTER: Krug D

PROVIDER: S-EPMC10212861 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Robotic stereotactic body radiotherapy for localized prostate cancer: final analysis of the German HYPOSTAT trial.

Krug David D Imhoff Detlef D Haidenberger Alfred A Heßler Nicole N Schäfer Jane J Huttenlocher Stefan S Chatzikonstantinou Georgios G Fürweger Christoph C Ramm Ulla U König Inke R IR Chun Felix F Staehler Michael M Rödel Claus C Muacevic Alexander A Vonthein Reinhard R Dunst Jürgen J Blanck Oliver O

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 20230209 6

<h4>Purpose</h4>We report results of the first German prospective multicenter single-arm phase II trial (ARO 2013-06; NCT02635256) of hypofractionated robotic stereotactic body radiotherapy (SBRT) for patients with localized prostate cancer (HYPOSTAT).<h4>Methods</h4>Patients eligible for the HYPOSTAT study had localized prostate cancer (cT1‑3 cN0 cM0), Gleason score ≤ 7, prostate-specific antigen (PSA) ≤ 15 ng/ml, prostate volume ≤ 80 cm<sup>3</sup>, and an International Prostate Symptom Score ...[more]

PMID: 36757424

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Project description:BACKGROUND:Stereotactic body radiotherapy (SBRT) for localized prostate cancer has potential advantages over traditional radiotherapies. Herein, the authors compared national trends in use, complications, and costs of SBRT with those of traditional radiotherapies. METHODS:The authors identified men who underwent SBRT, intensity-modulated radiotherapy (IMRT), brachytherapy, and proton beam therapy as primary treatment of prostate cancer between 2004 and 2011 from Surveillance, Epidemiology, and End Results Program (SEER)-Medicare linked data. Temporal trend of therapy use was assessed using the Cochran-Armitage test. Two-year outcomes were compared using the chi-square test. Median treatment costs were compared using the Kruskal-Wallis test. RESULTS:A total of 542 men received SBRT, 9647 received brachytherapy, 23,408 received IMRT, and 800 men were treated with proton beam therapy. There was a significant increase in the use of SBRT and proton beam therapy (P<.001), whereas brachytherapy use decreased (P<.001). A higher percentage of patients treated with SBRT and brachytherapy had low-grade cancer (Gleason score???6 vs???7) compared with individuals treated with IMRT and proton beam therapy (54.0% and 64.2% vs 35.2% and 49.6%, respectively; P<.001). SBRT compared with brachytherapy and IMRT was associated with equivalent gastrointestinal toxicity but more erectile dysfunction at 2-year follow-up (P<.001). SBRT was associated with more urinary incontinence compared with IMRT and proton beam therapy but less compared with brachytherapy (P<.001, respectively). The median cost of SBRT was $27,145 compared with $17,183 for brachytherapy, $37,090 for IMRT, and $54,706 for proton beam therapy (P<.001). CONCLUSIONS:The use of SBRT and proton beam therapy for localized prostate cancer has increased over time. Despite men of lower disease stage undergoing SBRT, SBRT was found to be associated with greater toxicity but lower health care costs compared with IMRT and proton beam therapy. Cancer 2016;122:2496-504. © 2016 American Cancer Society.

Project description:Prostate cancer is the most common non-cutaneous cancer in males. There are a number of options for patients with localized early stage disease, including active surveillance for low-risk disease, surgery, brachytherapy, and external beam radiotherapy. Increasingly, external beam radiotherapy, in the form of dose-escalated and moderately hypofractionated regimens, is being utilized in prostate cancer, with randomized evidence to support their use. Stereotactic body radiotherapy, which is a form of extreme hypofractionation, delivered with high precision and conformality typically over 1 to 5 fractions, offers a more contemporary approach with several advantages including being non-invasive, cost-effective, convenient for patients, and potentially improving patient access. In fact, one study has estimated that if half of the patients currently eligible for conventional fractionated radiotherapy in the United States were treated instead with stereotactic body radiotherapy, this would result in a total cost savings of US$250 million per year. There is also a strong radiobiological rationale to support its use, with prostate cancer believed to have a low α/β ratio and therefore being preferentially sensitive to larger fraction sizes. To date, there are no published randomized trials reporting on the comparative efficacy of stereotactic body radiotherapy compared to alternative treatment modalities, although multiple randomized trials are currently accruing. Yet, early results from the randomized phase III study of HYPOfractionated RadioTherapy of intermediate risk localized Prostate Cancer (HYPO-RT-PC) trial, as well as multiple single-arm phase I/II trials, indicate low rates of late adverse effects with this approach. In patients with low- to intermediate-risk disease, excellent biochemical relapse-free survival outcomes have been reported, albeit with relatively short median follow-up times. These promising early results, coupled with the enormous potential cost savings and implications for resource availability, suggest that stereotactic body radiotherapy will take center stage in the treatment of prostate cancer in the years to come.

Project description:BackgroundUltra-hypofractionated regimens for definitive prostate cancer (PCa) radiotherapy are increasingly utilized due in part to promising safety and efficacy data complemented by greater patient convenience from a treatment course requiring fewer sessions. As such, stereotactic body radiation therapy (SBRT) is rapidly emerging as a standard definitive treatment option for patients with localized PCa. The commercially available magnetic resonance linear accelerator (MR-LINAC) integrates MR imaging with radiation delivery, providing several theoretical advantages compared to computed tomography (CT)-guided radiotherapy. MR-LINAC technology facilitates improved visualization of the prostate, real-time intrafraction tracking of prostate and organs-at-risk (OAR), and online adaptive planning to account for target movement and anatomical changes. These features enable reduced treatment volume margins and improved sparing of surrounding OAR. The theoretical advantages of MR-guided radiotherapy (MRgRT) have recently been shown to significantly reduce rates of acute grade ≥ 2 GU toxicities as reported in the prospective randomized phase III MIRAGE trial, which compared MR-LINAC vs CT-based 5 fraction SBRT in patients with localized PCa (Kishan et al. JAMA Oncol 9:365-373, 2023). Thus, MR-LINAC SBRT-utilizing potentially fewer treatments-is warranted and clinically relevant for men with low or intermediate risk PCa electing for radiotherapy as definitive treatment.Methods/designA total of 136 men with treatment naïve low or intermediate risk PCa will be randomized in a 1:1 ratio to 5 or 2 fractions of MR-guided SBRT using permuted block randomization. Randomization is stratified by baseline Expanded PCa Index Composite (EPIC) bowel and urinary domain scores. Patients undergoing 5 fractions will receive 37.5 Gy to the prostate over 10-14 days and patients undergoing 2 fractions will receive 25 Gy to the prostate over 7-10 days. The co-primary endpoints are GI and GU toxicities as measured by change scores in the bowel and urinary EPIC domains, respectively. The change scores will be calculated as pre-treatment (baseline) score subtracted from the 2-year score.DiscussionFORT is an international, multi-institutional prospective randomized phase II trial evaluating whether MR-guided SBRT delivered in 2 fractions versus 5 fractions is non-inferior from a gastrointestinal (GI) and genitourinary (GU) toxicity standpoint at 2 years post-treatment in men with low or intermediate risk PCa.Trial registrationClinicaltrials.gov identifier: NCT04984343 . Date of registration: July 30, 2021.Protocol version4.0, Nov 8, 2022.

Project description:BackgroundMultiple phase I-II clinical trials have reported on the efficacy and safety of prostate stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer. However, few have reported outcomes for prostate SBRT using periprostatic hydrogel spacer (SpaceOAR; Augmenix). Herein, we report safety and efficacy outcomes from our institutional prostate SBRT experience with SpaceOAR placement.MethodsFifty men with low- or intermediate-risk prostate cancer treated at a single institution with linear accelerator-based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) were included. All patients underwent SpaceOAR and fiducial marker placement followed by pre-treatment MRI. Toxicity assessments were conducted at least weekly while on treatment, 1 month after treatment, and every follow-up visit thereafter. Post-treatment PSA measurements were obtained 4 months after SBRT, followed by every 3-6 months thereafter. Acute toxicity was documented per RTOG criteria.ResultsMedian follow up time was 20 (range 4-44) months. Median PSA at time of diagnosis was 7.4 (2.7-19.5) ng/ml. Eighteen men received 6 months of ADT for unfavorable intermediate risk disease. No PSA failures were recorded. Median PSA was 0.9 ng/mL at 20 months; 0.08 and 1.32 ng/mL in men who did and did not receive ADT, respectively. Mean prostate-rectum separation achieved with SpaceOAR was 9.6 ± 4 mm at the prostate midgland. No grade ≥ 3 GU or GI toxicity was recorded. During treatment, 30% of men developed new grade 2 GU toxicity (urgency or dysuria). These symptoms were present in 30% of men at 1 month and in 12% of men at 1 year post-treatment. During treatment, GI toxicity was limited to grade 1 symptoms (16%), although 4% of men developed grade 2 symptoms during the first 4 weeks after SBRT. All GI symptoms were resolving by the 1 month post-treatment assessment and no acute or late rectal toxicity was reported > 1 month after treatment.ConclusionsPeriprostatic hydrogel placement followed by prostate SBRT resulted in minimal GI toxicity, and favorable early oncologic outcomes. These results indicate that SBRT with periprostatic spacer is a well-tolerated, safe, and convenient treatment option for localized prostate cancer.

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:Radiotherapy is an increasingly preferred treatment option for localized prostate cancer, and stereotactic body radiation therapy (SBRT) a relatively established modality of therapeutic irradiation. The present study analyzes the toxicity and biochemical efficacy of SBRT in 100 consecutive prostate cancer patients treated with CyberKnife Robotic Radiosurgery System.One hundred patients were treated with SBRT at the Radiation Oncology department of San Bortolo Hospital, Vicenza, Italy. All patients included in this IRB-approved protocol-driven prospective study had biopsy-proven prostate cancer. Risk category was low in 41, intermediate in 42, and high in 17 patients. The patients were treated with CyberKnife-SBRT (CK-SBRT), the prescription dose was 35 Gy in five fractions, corresponding to 92 Gy in 2-Gy fractions (?/? =1.5 Gy); 29 patients also received androgen deprivation therapy (ADT).Median follow-up was 36 months (range, 6-76 months). Acute Grade 2 genitourinary and gastrointestinal toxicity occurred in respectively 12% and 18% of the patients; there were no Grade 3 or higher acute toxicities. Late Grade 1, 2, and 3 genitourinary toxicities occurred in 4%, 3%, and 1% of the patients, respectively; late Grade 1 gastrointestinal toxicity occurred in two patients and Grade 2 toxicity in one patient; no late gastrointestinal toxicities of grade 3 or 4 were observed. Median PSA nadir was 0.45 ng/ml at 36 months for all patients. In the SBRT-monotherapy group, the median PSA nadir at 36 months was 0.62 ng/ml; in the ADT-SBRT group, it was 0.18 ng/ml. Four patients had clinical recurrence: one local, two lymph nodes, and one to the bone. Ninety-six patients had no evidence of biochemical or clinical recurrence. A benign PSA bounce of median 1.08 ng/ml occurred in 12% of the 71 SBRT monotherapy patients at a mean 23 months (range, 18-30 months).In this study CK-SBRT has provided promising outcomes in localized prostate cancer with good PSA response, minimal toxicity and patient inconvenience.

Dataset Information

Robotic stereotactic body radiotherapy for localized prostate cancer: final analysis of the German HYPOSTAT trial.

Purpose

Methods

Results

Conclusion

Publications

Robotic stereotactic body radiotherapy for localized prostate cancer: final analysis of the German HYPOSTAT trial.

Similar Datasets

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