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EAU Annual Congress 2023

EAU 2023: Patient with High-Risk Localized Disease, M0 on Conventional Imaging but One Bone Lesion on PSMA PET/CT: Arguments for a Radiotherapeutic Approach +/- Systemic Treatment

(UroToday.com) The 2023 EAU annual meeting included a joint session of the EAU and the Advanced Prostate Cancer Consensus, featuring a presentation by Dr. Thomas Zilli discussing how among patients with high-risk localized disease, M0 on conventional imaging but one bone lesion on PSMA PET/CT, we should be treating these patients with radiotherapy +/- systemic treatment. Dr. Zilli started his presentation by highlighting that the addition of local radiotherapy to continuous androgen suppression improves overall survival in high-risk or locally-advanced prostate cancer compared to systemic therapy alone. This is based off of data from the SPCG-7 trial1 and the NCIC/MRC trial:2

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The benefit of androgen deprivation and duration of use with radiotherapy has been recently further strengthened and clarified by the publication of the MARCAP meta-analysis.3 This individual patient data meta-analysis included 12 eligible trials on 10,853 patients with a median follow-up of 11.4 years (IQR 9.0-15.0), over which time the addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0.83, 95% CI 0.77-0.89), as did adjuvant ADT prolongation (HR 0.84, 95% CI 0.78-0.91), but neoadjuvant ADT extension did not (HR 0.95, 95% CI 0.83-1.09). 

Additionally, the benefit of radiotherapy dose escalation was confirmed with the 2022 publication of the HEAT individual patient-data network meta-analysis.4 This analysis included 13 multicenter trials, with 11,862 patients. Patients received one of the six permutations of low-dose radiotherapy (64 to <74 Gy) ± short-term ADT or long-term ADT, high-dose radiotherapy (≥74 Gy), or high-dose radiotherapy ± short-term ADT or long-term ADT. Dose escalation up to 79.2 Gy alone or combined with ADT improved biochemical RFS, but not MFS or OS. Ultimately, the combination of high-dose radiotherapy and long-term ADT is the best treatment strategy:

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The benefit of treatment intensification was confirmed with a meta-analysis from 2 STAMPEDE phase III RCTs of high-risk localized prostate cancer treated with either abiraterone or enzalutamide.5 Local radiotherapy (74 Gy in 37 fractions to the prostate and seminal vesicles or the equivalent using hypofractionated schedules) was mandated for node-negative and encouraged for node-positive disease. There were 1,974 patients randomized and over a median follow-up of 72 months (IQR 60–84), metastasis-free survival was significantly longer in the combination-therapy groups (median not reached, IQR NE–NE) than in the control groups (not reached, 97–NE; HR 0.53, 95% CI 0.44–0.64). Overall survival (median not reached [IQR NE–NE] in the combination-therapy groups vs not reached [103–NE] in the control groups; HR 0.60, 95% CI 0.48–0.73):

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For cM0 high-risk disease, the EAU guidelines suggest the following:

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Updated results of STAMPEDE Arm H (radiotherapy to the primary) were published in 2022.6 With a median follow up of 61.3 months, prostate radiotherapy continued to demonstrate overall survival benefit in patients with low metastatic burden (HR: 0.64, 95% CI: 0.52 - 0.79, p < 0.001), whereas no benefit was seen in patients with a high metastatic burden (HR: 1.11, 95% CI: 0.96 - 1.28, p = 0.164; interaction p = 0.001):

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To date, there is no high level data assessing loco-regional radiotherapy with SBRT to all PET positive metastatic sites, but retrospective studies suggest this is feasible with promising disease control rates. The follow is a summary of comprehensive radiotherapy ongoing clinical trials:

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Dr. Zilli concluded his presentation with the following take-home messages:

  • Dose escalated external beam radiotherapy with concomitant long-term ADT remains one of the mainstay treatments of high-risk locally advanced prostate cancer
  • Combination of 3 years of ADT and 2-years of abiraterone with radiotherapy is the new standard of care for very high-risk prostate cancer patients
  • Ongoing RCTs in the de novo M1 on PSMA PET/CT will help to define the role of:
    • Next-generation imaging
    • Systemic therapies combined with radiotherapy (type and duration)
    • Ablative metastasis directed therapy to all disease sites
  • Be careful of stage migration and the impact on treatment decisions: consider multidisciplinary discussion and inclusion in clinical trials or registries

 

Presented by: Thomas Zilli, MD, PhD, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 European Association of Urology (EAU) Annual Meeting, Milan, IT, Fri, Mar 10 – Mon, Mar 13, 2023.

Related Content: 
Alicia Morgans EAU 2023: Patient with High-Risk Localized Disease, M0 on Conventional Imaging but One Bone Lesion on PSMA PET/CT: How to Treat a Frail and Elderly Patient in this Situation
Maria De Santis EAU 2023: Patient with High-Risk Localized Disease, M0 on Conventional Imaging but One Bone Lesion on PSMA PET/CT: Systemic Therapy: What and for how long?
Eva Comperat EAU 2023: Patient with High-Risk Localized Disease, M0 on Conventional Imaging but One Bone Lesion on PSMA PET/CT: Subtypes of Prostate Cancer and How They Change our Management
Bertrand Tombal EAU 2023: Patient with High-Risk Localized Disease, M0 on Conventional Imaging but One Bone Lesion on PSMA PET/CT: Arguments for a Surgical Approach +/- Radiotherapy +/- Systemic Treatment

References

  1. Widmark A, Klepp O, Solberg A, et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): An open randomized phase III trial. Lancet. 2009 Jan 24;373(9660):301-308.
  2. Warde P, Mason M, Ding K, et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: A randomized, phase 3 trial. Lancet. 2011 Dec 17;378(9809):2104-2111.
  3. Kishan AU, Sun Y, Hartman H, et al. Androgen deprivation therapy use and duration with definitive radiotherapy for localized prostate cancer: An individual patient data meta-analysis. Lancet Oncol. 2022 Feb;23(2):304-316.
  4. Kishan AU, Wang X, Sun Y, et al. High-dose radiotherapy or androgen deprivation therapy (HEAT) as treatment intensification for localized prostate cancer: An individual patient-data network meta-analysis from the MARCAP Consortium. Eur Urol. 2022 Jul;82(1):106-114.
  5. Attard G, Murphy L, Clarke NW, et al. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: A meta-analysis of primary results from two randomized controlled phase 3 trials of the STAMPEDE platform protocol. Lancet 2022 Jan 29;399(10323):447-460.
  6. Parker CC, James ND, Brawley CD, et al. Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial. PLoS Medicine. 2022;19(6):e1003998.