EAU 2024: State-of-the-Art Lecture: Local Therapy in mHSPC: Who Does Really Benefit?

(UroToday.com) The 2024 European Association of Urology (EAU) annual meeting featured a plenary session on personalized approaches in high-risk and metastatic prostate cancer, and a state of the art lecture by Dr. Alberto Bossi discussing who benefits from local therapy in metastatic hormone sensitive prostate cancer (mHSPC). Dr. Bossi emphasized that the EAU guidelines for the first-line treatment of hormone sensitive metastatic disease state that we should “offer ADT combined with prostate radiotherapy (using up to the equivalent of 72 Gy in 2 Gy fractions) to patients whose first presentation is M1 disease and who have low volume of disease by the CHAARTED criteria” (Strength rating: Strong). Moreover, “do not offer ADT combined with surgery to M1 patients outside of clinical trials” (Strength rating: Strong), and “only offer metastasis directed therapy to M1 patients within a clinical trial setting or a well-designed prospective cohort study” (Strength rating: Strong).

In 2019, Burdett and colleagues¹ published the STOPCAP meta-analysis, assessing the effect of adding prostate radiotherapy to ADT. Ultimately, the optimal cut-off was 4 bone metastases, with an absolute survival improvement of 7% at 3 years:

Dr. Bossi then discussed the PEACE-1 trial in detail,² emphasizing the presentation from ASCO 2023 discussing the efficacy and safety of prostate radiotherapy for patients with low volume, de novo mCSPC. Eligible patients for PEACE-1 had de novo mCSPC and could have received up to 3 months of ADT prior to randomization. A total of 1,173 men were randomized 1:1:1:1 as shown below. Abiraterone treatment consisted of 1,000 mg/day with prednisone 5 mg twice per day until disease progression or intolerance and was administered along with docetaxel for patients who underwent chemotherapy. Radiotherapy to the prostate was delivered in 37 fractions for a cumulative dose of 74 Gy after patients completed docetaxel if receiving chemotherapy.

The addition of prostate radiotherapy to standard of care + abiraterone was associated with significant rPFS benefits (median 7.5 versus 4.4 years, p = 0.02). Conversely, the addition of radiotherapy to standard of care alone was not associated with rPFS benefits (median 2.6 versus 3.0 years; HR: 1.11, 95% CI: 0.67 – 1.84, p=0.61).

The addition of prostate radiotherapy to either standard of care alone or standard of care + abiraterone was not associated with OS improvements. In the standard of care + abiraterone arms, addition of prostate radiotherapy was associated modest, non-significant OS benefits (HR: 0.77, 95% CI: 0.51 – 1.16, p=0.21). Similarly, addition of prostate radiotherapy to standard of care alone did not improve OS in low volume patients (HR: 1.18, 95% CI: 0.81- 1.71, p=0.39):

In the low volume population, serious genitourinary events were not infrequent, notably with 27 patients that did not receive radiotherapy undergoing a TURP, compared to only 4 patients among those that underwent radiotherapy:

In both the low volume and overall population, time to serious genitourinary events was improved with the addition of radiotherapy:

Delving deeper into the TURP data, Dr. Bossi notes that this is not necessarily a benign procedure, with the EAU guidelines suggesting that 4.9% of patients have clot retention, 4.5% acute urinary retention, 4.1% urinary tract infection, 2.9% require a blood transfusion, and 0.8% have TUR syndrome.

Further discussing the PEACE-1 trial, Dr. Bossi emphasized that the addition of prostate radiotherapy to standard of care + abiraterone or standard of care alone was associated with significant improvements in time to castration resistance in the low-volume (median 3.4 versus 2.5 years; HR 0.74, 95% CI 0.60 – 0.92, p = 0.007) and overall cohorts (median: 2.5 versus 1.9 years; HR 0.79, 95% CI 0.69 – 0.90, p = 0.007):

A similar toxicity profile was observed among patients receiving radiotherapy versus not, as summarized below:

Aligning results from the STAMPEDE and PEACE-1 trials for assessing the impact of prostate radiotherapy in the setting of low volume, de-novo, mHSPC, the following table summarizes the findings:

Similarly, the following table is provided for high-volume, de-novo, mHSPC and the role of radiotherapy:

Dr. Bossi concluded his presentation by discussing who really benefits from local therapy in mHSPC with the following conclusions:

Who really benefits from local therapy in mHSPC depends on which endpoint your patient considers important:
- Overall survival? Count bone metastasis on bone scan
- Prevent severe GU events? Discuss prostate radiotherapy
- Report castration-resistance? Discuss prostate radiotherapy

Presented by: Alberto Bossi, MD, Gustave Roussy Cancer, Université Paris-Saclay, Villejuif, France

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 European Association of Urology (EAU) annual congress, Paris, France, April 5^th - April 8^th, 2024

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