(UroToday.com) The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on the management of metastatic hormone sensitive prostate cancer (mHSPC) and a presentation by Dr. Karim Fizazi discussing that when low-volume disease on conventional imaging becomes high-volume on next-generation imaging in mHSPC, we should treat these patients like low volume patients.
Dr. Fizazi notes that the first issue is that instead of like all other cancers, we currently tend to treat M1 prostate cancer according to disease volume (metastatic burden). For example, there is robust evidence for selecting prostate radiotherapy only for men with <4 bone metastases based on data from the STAMPEDE trial.1 Furthermore, systemic treatment namely the second generation androgen receptor axis inhibitors (abiraterone, apalutamide, and enzalutamide) are active regardless of cancer burden, whereas docetaxel is debated based on subgroup findings (STAMPEDE: all patients; CHAARTED: high-volume disease only).
Dr. Fizazi highlighted that based on additional analyses of CHAARTED and GETUG-AFU15, we are able to identify men more likely to benefit from early docetaxel by assessing the burden of metastatic castrate naïve prostate cancer.2 Specifically, patients with low-volume disease showed much longer overall survival, without evidence that docetaxel improved overall survival. Thus, these patients which represent M1 relapse and low-volume oligometastatic disease, are the outlier with median overall survival of 7.7 years (95% CI 6.7-10.6), according to Dr. Fizazi:
The second issue highlighted by Dr. Fizazi is next generation imaging (including PSMA PET/CT, Choline PET/CT, whole body MRI, etc) given that more lesions are often seen with these new modalities, often performed upfront without previous conventional imaging. Importantly, all available evidence from phase 3 trials was obtained with conventional imaging. So, when conventional imaging shows low burden of disease and next generation imaging shows high burden of disease, how should we treat these patients?
- Prostate radiotherapy?
- Second generation androgen receptor axis inhibitor?
- Docetaxel?
- Triple systemic therapy?
- Metastases-directed therapy?
Dr. Fizazi suggests that we should likely treat these patients with prostate radiotherapy based on a potential overall survival benefit, possible better local control, and modest additional toxicity. We should definitely treat these patients with second generation androgen receptor axis inhibitors given that all RCTs in this disease space have been positive, however, the optimal duration of treatment is unknown. We should not treat these patients with docetaxel since docetaxel doublet therapy is now out of favor. We may consider treating these patients with triplet therapy, which should be considered on a patient by patient basis (particularly for young, fit patients with 2-4 bone metastasis). However, rPFS is improved with triplet therapy and OS data is immature to date. With regards to metastasis directed therapy, we are in urgent need of clinical trial data. Dr. Fizazi’s recommendations are summarized in the following table:
Dr. Fizazi concluded his presentation by stating that at the end of the day, it will be most important to move away from the volume concept toward biomarker stratification as soon as possible.
Presented by: Karim Fizazi, MD, PhD, Institut Gustave Roussy, Paris, France
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 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Annual Hybrid Meeting, Lugano, Switzerland, Thurs, Apr 28 – Sat, Apr 30, 2022.
References:- Ali A, Hoyle A, Haran AM, et al. Association of bone metastatic burden with survival benefit from prostate radiotherapy in patients with newly diagnosed metastatic prostate cancer: A secondary analysis of a randomized clinical trial. JAMA Oncol. 2021 Apr 1;7(4):555-563.
- Gravis G, Boher JM, Chen YH, et al. Burden of metastatic castrate naïve prostate cancer patients, to identify men more likely to benefit from early docetaxel: Further analysis of CHAARTED and GETUG-AFU15 studies. Eur Urol 2018 Jun;73(6);847-855.