A Phase II Trial of Stereotactic Body Radiation Therapy and Androgen Deprivation for Oligometastases in Prostate Cancer (SBRT-SG 05) - ScienceDirect

Summary

This article describes a Phase II clinical trial called SBRT-SG 05 that evaluated the use of stereotactic body radiation therapy (SBRT) combined with androgen deprivation therapy (ADT) in patients with oligometastatic prostate cancer. Here are the key points:

• 1. Study design:
• - Two cohorts:
•   1) Main cohort of 67 patients with hormone-sensitive prostate cancer
•   2) Exploratory cohort of 14 patients with castration-resistant prostate cancer
• - Patients received SBRT to metastatic lesions and ADT for at least 24 months
• - Median follow-up was 40 months
• 2. Main results:
• - 3-year local recurrence-free survival: 92.5% (62/67) in main cohort, 85.7% (12/14) in exploratory cohort
• - In main cohort at 3 years:
•   - Biochemical relapse-free survival: 50.6%
•   - Metastasis progression-free survival: 67%
• - Exploratory cohort had lower metastasis progression-free survival rates
• 3. Toxicity:
• - No grade III or higher toxicity
• - Only 2 patients (2.4%) developed grade II toxicity
• 4. Conclusions:
• - The combination of SBRT and ADT appears safe and effective for oligometastatic prostate cancer
• - Shows promise for both hormone-sensitive and castration-resistant patients
• - Further validation studies needed, especially for castration-resistant patients
• 5. Limitations:
• - Small sample size, especially in exploratory cohort
• - Lack of randomization
• - Some radiation doses may be considered suboptimal by current standards

The authors suggest this combined approach may be an effective strategy to improve outcomes and delay the need for more intensive systemic therapies in oligometastatic prostate cancer patients.

Figures

The study includes three main figures, which I'll describe in layman's terms:

Figure 1: Kaplan-Meier local recurrence-free survival

This graph shows how well the treatment (SBRT + ADT) prevented cancer from coming back in the same spots that were treated.

Explanation: The vertical axis shows the percentage of patients without local recurrence, and the horizontal axis shows time in months. There are two lines on the graph - one for the main group (hormone-sensitive patients) and one for the exploratory group (castration-resistant patients). Both lines start at 100% and gradually decrease over time, but they stay quite high, even after 3 years. This means that for most patients, the cancer didn't come back in the treated areas.

Figure 2: Kaplan-Meier biochemical relapse-free survival

This graph shows how long patients went without their PSA (prostate-specific antigen) levels rising again after treatment.

Explanation: Similar to Figure 1, but this time focusing on PSA levels. A rising PSA can indicate that the cancer is becoming active again. The graph shows that for many patients, especially in the main group, PSA levels stayed low for a considerable time after treatment. However, the line drops more quickly than in Figure 1, suggesting that some patients had rising PSA even though the treated spots didn't show visible cancer return.

Figure 3: Kaplan-Meier metastasis progression-free survival

This graph shows how long patients went without their cancer spreading to new areas in the body.

Explanation: This graph looks at whether the cancer spread to new locations after the initial treatment. The main group (hormone-sensitive patients) does better than the exploratory group (castration-resistant patients). For the main group, about 2/3 of patients still had no new metastases after 3 years. The exploratory group's line drops more quickly, showing that these patients tended to develop new metastases sooner.

Overall, these graphs suggest that the treatment was quite effective at controlling cancer in the treated areas and delaying the spread of cancer, especially for hormone-sensitive patients. However, they also show that the treatment doesn't work equally well for everyone, and that castration-resistant patients tend to have less favorable outcomes. 

Tables

The study doesn't explicitly list tables in the excerpt provided, but it does contain several important data sets that could be considered as tables. I'll describe the main data groupings as if they were tables and explain them in layman's terms:

1. Baseline characteristics of patients (Table 1 in the document)

This table shows the key information about the patients in the study when they started treatment.

Explanation: It includes things like the patients' age, race, PSA levels at diagnosis, cancer stage, and risk group. This information helps us understand what kind of patients were in the study. For example, most patients were Caucasian, in their 60s, and had intermediate to high-risk prostate cancer.

2. Description of treatment received and time to diagnosis of oligorecurrent disease (Table 2)

This table explains what treatments patients had before joining the study and how long it took for their cancer to come back in just a few spots (oligorecurrent).

Explanation: It shows that patients had various initial treatments like radiation or surgery. Most patients had some hormone therapy before. On average, it took about 5-6 years from the initial diagnosis for the cancer to come back as oligometastatic disease.

3. Characteristics of the lesions treated and radiation therapy scheme used (Table 3)

This table describes the cancer spots (lesions) that were treated with radiation in the study.

Explanation: It shows how many lesions each patient had (most had 1-3), where they were located (mostly in bones and lymph nodes), and how the radiation was given. For example, some patients got one big dose of radiation, while others got several smaller doses.

4. Survival and progression data (not explicitly presented as a table, but could be considered as one)

This data set shows how patients did after treatment - how long they went without cancer coming back or spreading.

Explanation: It includes information like how many patients had their cancer come back in the treated spots (very few), how many had their PSA rise again, and how many had their cancer spread to new areas. It shows that the treatment worked well for many patients, especially those whose cancer still responded to hormone therapy.

5. Toxicity data (not explicitly presented as a table, but mentioned in the results)

This data set shows how safe the treatment was.

Explanation: It tells us about side effects from the treatment. The study found that the treatment was very safe - no patients had severe side effects, and only 2 out of 81 patients had moderate side effects.

These data sets help us understand who was in the study, what treatment they received, and how well it worked, both in terms of controlling the cancer and avoiding side effects.

Oligometastatic Definition

Based on the information provided in the study, the definition of oligometastatic prostate cancer used was:

• 1. Number of metastases: Less than 5 metastases
• 2. Location of metastases: Bone and/or lymph node metastases
• 3. Imaging modality: Detected on choline positron emission tomography (PET)/computed tomography (CT) and/or whole-body diffusion-weighted magnetic resonance imaging (MRI)
• 4. Timing: After primary treatment (indicating this is oligorecurrent disease)
• 5. Exclusion: Patients with visceral metastases were excluded

The study included two cohorts:
1. A principal cohort of patients with oligorecurrent hormone-sensitive prostate cancer
2. An exploratory cohort of patients with oligorecurrent castration-resistant prostate cancer

Additionally, the inclusion criteria specified:
- More than 1 year from primary treatment to biochemical recurrence
- Prostate-specific antigen (PSA) doubling time of more than 2 months

This definition aligns with common clinical definitions of oligometastatic prostate cancer, which typically consider 3-5 or fewer metastases as the cutoff for oligometastatic disease. The use of advanced imaging techniques (choline PET/CT or whole-body MRI) is also consistent with current practices for detecting oligometastatic disease in prostate cancer.

Bone v. Lymph Node Mets

The study differentiated between bone and lymph node metastases. While the definition of oligometastatic disease included both bone and lymph node metastases, the researchers provided specific information about the distribution of metastases in the treated patients. Here's what the study reported:

1. Metastasis site distribution:
   - Bone: 42% (42/100) in the primary cohort, 38.5% (10/26) in the exploratory cohort
   - Lymph node: 55% (55/100) in the primary cohort, 61.5% (16/26) in the exploratory cohort
   - Bone and lymph node: 3% (3/100) in the primary cohort, 0% in the exploratory cohort

2. Metastasis location:
   - Pelvis: 62% in the primary cohort, 65.4% in the exploratory cohort
   - Abdomen (retroperitoneum): 9% in the primary cohort, 3.9% in the exploratory cohort
   - Spine: 17% in the primary cohort, 15.4% in the exploratory cohort
   - Rib: 4% in the primary cohort, 3.9% in the exploratory cohort
   - Thorax (mediastinum): 3% in the primary cohort, 3.9% in the exploratory cohort
   - Others: 4% in the primary cohort, 7.7% in the exploratory cohort

3. Radiation dosing:
   The study used different radiation dosing schedules depending on the location of the metastases:
   - Vertebral metastases: 1 × 16 to 18 Gy or 3 × 8 to 9 Gy
   - Lymph node metastases: 3 × 10 to 11 Gy or 6 × 7.5 Gy
   - Non-spinal bone metastases: 1 × 16 Gy or 3 × 10 Gy

While the study did differentiate between bone and lymph node metastases in terms of location and treatment approach, it doesn't appear that the researchers analyzed outcomes specifically based on the type of metastasis (bone vs. lymph node). The overall results were reported for all metastases together.

Imaging Modes

Based on the information provided in the study, there was no specific analysis or comparison of the diagnostic accuracy of different imaging modalities in determining oligometastatic burden. However, the study does mention the imaging techniques used for diagnosis:

1. Primary imaging modalities:
   - Choline PET/CT (Positron Emission Tomography/Computed Tomography)
   - Whole-body diffusion-weighted MRI (Magnetic Resonance Imaging)

2. Usage of imaging modalities:
   - In the primary cohort, 94% (63/67) of patients were diagnosed using Choline PET/CT, and 6% (4/67) using whole-body MRI.
   - In the exploratory cohort, 100% (14/14) of patients were diagnosed using Choline PET/CT.

3. Follow-up imaging:
   - The study mentions that conventional imaging was performed at 3, 6, and 12 months and every year thereafter if there was no evidence of disease progression or symptoms.
   - Advanced imaging tests were performed during follow-up at the discretion of the investigator and were not mandatory at the time of establishing disease progression.
   - In both cohorts, 43% of patients were followed up after SBRT with advanced imaging tests.

The study does not provide a comparison of the accuracy or effectiveness of these different imaging modalities in detecting oligometastatic disease. It also doesn't discuss any potential limitations or differences in sensitivity or specificity between Choline PET/CT and whole-body MRI.

This lack of comparison between imaging modalities is a limitation of the study, as different imaging techniques can have varying sensitivities in detecting small metastases. Future studies might benefit from a more standardized approach to imaging or a direct comparison of different imaging modalities in detecting oligometastatic disease in prostate cancer.

It's worth noting that since this study was conducted, newer imaging techniques like PSMA PET/CT have become more widely available and are now often preferred for detecting prostate cancer metastases due to their higher sensitivity and specificity.

SBRT

Stereotactic body radiation therapy (SBRT) is an advanced form of external beam radiation therapy used to treat various types of cancer. Here are the key features of SBRT:

1. Precision targeting: SBRT uses highly focused beams of radiation to target tumors with extreme accuracy, often within millimeters.

2. High doses: It delivers very high doses of radiation in fewer treatment sessions compared to conventional radiation therapy.

3. Fewer treatments: While conventional radiation therapy might involve 20-40 sessions, SBRT typically requires only 1-5 treatments.

4. 3D imaging: SBRT utilizes advanced imaging techniques like CT, MRI, or PET scans to create detailed 3D maps of the tumor and surrounding tissues.

5. Motion management: It employs various techniques to account for organ motion during treatment, such as respiratory gating or tracking systems.

6. Multiangle delivery: Radiation is delivered from multiple angles around the body, converging on the tumor while minimizing exposure to healthy tissues.

7. Immobilization: Patients are carefully positioned and sometimes immobilized to ensure precise targeting.

8. Real-time imaging: Many SBRT systems use real-time imaging during treatment to verify target location and make adjustments if needed.

9. Versatility: SBRT can be used to treat tumors in various parts of the body, including lungs, liver, spine, and prostate.

10. Non-invasive: As an external beam therapy, SBRT is non-invasive and does not require surgery.

SBRT's ability to deliver high doses of radiation precisely to tumors while sparing surrounding healthy tissue makes it an effective option for treating certain cancers, especially when surgery is not feasible or desirable. It's particularly useful for small, well-defined tumors or oligometastatic disease, as described in the study you asked about.

Clinical Impact

Assuming larger scale trials verify the results of this study, the impact on clinical care of prostate cancer (PCa) could be significant. Here are some potential implications:

1. Treatment paradigm shift: This could lead to a more aggressive approach in treating oligometastatic prostate cancer, combining local therapy (SBRT) with systemic therapy (ADT) instead of relying solely on systemic treatments.

2. Delayed disease progression: The high rates of local control and promising progression-free survival could mean delaying the onset of more widespread metastatic disease, potentially improving quality of life and overall survival.

3. Personalized treatment: It may encourage more tailored treatment approaches for patients with limited metastatic disease, moving away from a one-size-fits-all approach to metastatic prostate cancer.

4. Extended use of ADT: The study used ADT for at least 24 months, which could influence the duration of hormone therapy in clinical practice for oligometastatic patients.

5. Increased use of advanced imaging: To identify suitable candidates for this approach, there might be increased use of advanced imaging techniques like choline PET/CT or whole-body MRI in patients with biochemical recurrence.

6. Expanded role of radiation oncology: This could lead to a larger role for radiation oncologists in the management of metastatic prostate cancer, particularly in multidisciplinary treatment planning.

7. Quality of life considerations: If this approach delays the need for more intensive systemic therapies, it could positively impact patient quality of life.

8. Cost-effectiveness: While initial costs might be higher due to SBRT, if this approach delays disease progression and the need for expensive systemic therapies, it could prove cost-effective in the long run.

9. Clinical trial design: Future trials in metastatic prostate cancer might incorporate local therapies like SBRT more frequently, even in the setting of limited metastatic disease.

10. Management of castration-resistant disease: The exploratory cohort results, if verified, could open new treatment options for patients with oligometastatic castration-resistant prostate cancer.

11. Follow-up protocols: This might influence how patients are monitored after primary treatment, with more emphasis on early detection of oligometastatic disease.

12. Multidisciplinary approach: It could encourage closer collaboration between urologists, medical oncologists, and radiation oncologists in managing prostate cancer patients.

These potential impacts underscore the importance of larger, randomized controlled trials to confirm these findings and further refine the role of combined SBRT and ADT in oligometastatic prostate cancer management.

A Phase II Trial of Stereotactic Body Radiation Therapy and Androgen Deprivation for Oligometastases in Prostate Cancer (SBRT-SG 05) - ScienceDirect

sciencedirect.com

M Guckenberger

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Purpose

SBRT-Spanish Group-05 (ClinicalTrials.gov.Identifier: NCT02192788) is a collaborative (SBRT-SG, Grupo de Investigación Clínica en Oncología Radioterápica, and Sociedad Española de Oncología Radioterápica) [RT-SG, Clinical Research Group in Radiation Oncology, and Spanish Society of Radiation Oncology] prospective multicenter phase II trial testing stereotactic body radiation therapy (SBRT) and androgen deprivation therapy (ADT) in patients with oligorecurrent prostate cancer.

Methods and Materials

Two cohorts of patients with prostate cancer in an oligorecurrent stage (hormone-sensitive in the principal cohort and castration-resistant in the exploratory cohort) were assigned to receive ADT and SBRT for at least 24 months from the time of the enrollment. Concomitant treatment with chemotherapy, abiraterone, or enzalutamide was not allowed. Oncologic outcomes were assessed in both cohorts. Toxicity was prospectively analyzed.

Results

From 2014 to 2019, 81 patients with a total of 126 lesions from 14 centers met the inclusion criteria, 14 of whom were castration-resistant. With a median follow-up of 40 months (12-58 months), 3-year local recurrence-free survival was 92.5% (95% CI, 79.9%-96.3%) and 85.7% (95% CI, 48.2%-95.6%) in the principal and exploratory cohorts, respectively. In the principal cohort, biochemical relapse-free survival and metastasis progression-free survival at 1, 2, and 3 years were 91% (95% CI, 81%-95.8%), 73.7% (95% CI, 61.1%-82.8%), 50.6% (95% CI, 36.2%-63.3%), and 92% (95% CI, 83%-97%), 81% (95% CI, 70%-89%), and 67% (95% CI, 53%-77%), respectively. In the exploratory cohort, metastasis progression-free survival at 1, 2, and 3 years was 64% (95% CI, 34%-83%), 43% (95% CI, 18%-66%), and 26% (95% CI, 7%-51%), respectively. None of the patients developed grade III or higher toxicity or symptoms related to local progression, and only 2 (2.4%) patients developed grade II toxicity.

Conclusions

The combination of SBRT and ADT is safe and shows favorable clinical outcomes in patients with hormone-sensitive and castration-resistant prostate cancer. Validation studies are needed in patients with castration-resistant prostate cancer.

Introduction

Since the oligometastatic disease stage was formally defined, technological advances in next-generation imaging and radiation oncology have fostered the use of stereotactic body radiation therapy (SBRT) as metastasis-directed therapy (MDT) in virtually all tumor histologies.¹ However, we cannot assume that the disease in these patients is limited to that detected using imaging techniques. Technically, a patient with oligometastatic cancer is still a patient with metastatic cancer and will therefore require systemic treatment.

In metastatic hormone-sensitive prostate cancer, SBRT may control macroscopic disease detected by imaging techniques, whereas androgen deprivation therapy (ADT) may control microscopic disease, as seen in the treatment of locally advanced prostate cancer. This approach can offer an optimized outcome, and a “therapeutic holiday” may also be proposed, during which the patient's testosterone levels can return to normal.² However, castration-resistant prostate cancer is not necessarily radiation-resistant, and MDT in the form of SBRT can help delay the switch to systemic treatment in patients with oligoprogression.³ In 2014, we implemented a prospective, nonrandomized phase II multicenter clinical trial to evaluate this therapeutic approach and test the combination of ADT and SBRT in oligometastatic prostate cancer in different clinical settings.

Section snippets

Methods and Materials

SBRT-Spanish Group-05 is a prospective multicenter phase II trial testing SBRT and androgen deprivation for oligometastasis in patients with prostate cancer, performed jointly by the SBRT Working Group of the Spanish Society of Radiation Oncology (Sociedad Española de Oncología Radioterápica, in its Spanish acronym) and the Radiation Oncology Clinical Research Group (Grupo de Investigación Clínica en Oncología Radioterápica, in its Spanish acronym). The study was approved by the ethics

Results

From July 2014 to December 2019, 81 patients from 14 Spanish centers with a total of 126 lesions met the inclusion criteria of this clinical trial; 67 patients with a total of 100 lesions were included in the principal cohort (oligorecurrent hormone-sensitive prostate cancer), and 14 with a total of 26 lesions were included in the exploratory cohort (oligorecurrent/oligoprogressive castration-resistant prostate cancer). The 2 groups were analyzed separately according to their characteristics

Discussion

The criteria for indicating MTD in patients with oligometastatic prostate cancer are currently based primarily on the number of metastases detected on prostate-specific membrane antigen (PSMA) PET/CT scan.⁷ The absence of a biological criterion may explain the rapid polymetastatic progression observed in some patients, especially those who have not received systemic treatment.⁸

Fortunately, there is growing interest in investigating biomarkers that could help select patients who would benefit

Conclusions

The combination of SBRT and ADT is safe and shows favorable clinical outcomes in patients with hormone-sensitive and castration-resistant prostate cancer. Validation studies are needed for patients with castration-resistant prostate cancer.

Disclosures

Antonio Conde-Moreno reports receiving consulting fees, honoraria for lectures, and support for attending meetings from Janssen, Astellas, Bayer, and Ipsen. Fernando L. Campos reports receiving consulting fees from Janssen Astellas and Bayer, and honoraria for lectures and support for attending meetings from Janssen, Astellas, Bayer, and Casen Recordati; BMS and AstraZeneca. Alfonso Gómez-Iturriaga reports receiving consulting fees from Bayer, Elekta, Astellas, and Janssen, honoraria for

Acknowledgments

We thank Laura Hidalgo, PhD (Medical Science Consulting, Valencia, Spain) for editing support.

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