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

(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. Alicia Morgans discussing how to treat frail patients with high-risk localized disease, M0 on conventional imaging but one bone lesion on PSMA PET/CT. When discussing the vulnerable and frail patient, it is important to define this specific phenotype.

Indeed, we live in an aging world, with a predicted 21 to >28% of the population (specifically in Europe and North America) expected to be older than 65 years of age in 2050. Dr. Morgans emphasized that prostate cancer disproportionately affects elderly men, with a median age at diagnosis of 66 years of age and the most frequent age range for diagnosis being 65-74 years of age. However, chronologic and biologic age are not the same.

 The International Society of Geriatric Oncology has published guidelines for the management of prostate cancer in elderly patients, providing key guidance. It is important for clinicians to understand the different steps in health status evaluation and the estimated time required to complete these evaluations.¹ Importantly, a mandatory initial step is to perform a G8 and a Mini-COG assessment:

The G8 screening tool highlights 8 specific items that clinicians address, including those pertaining to food intake, weight loss in the last 3 months, mobility, neuropsychological problems, body mass index, number of daily medications, personal consideration of health status, and age:

The benefit of the G8 screening tool is that we can identify patients who are going to do well, and those who will likely do poorly. In a prospective study by Kenis et al., 937 patients with cancer (9% with prostate cancer) were assessed with G8, with a normal screening score significantly associated with improved overall survival (HR 0.38, p < 0.001) versus those with an abnormal G8 score:²

Dr. Morgans then walked the audience through several of the pertinent survey questions from the 2022 APCCC meeting. The first question was: in patients with mHSPC who are >= 75 years old, do you recommend a geriatric assessment (assuming it is readily available) before choosing a treatment combination? 52% of respondents said yes, in the majority of patients; 48% of respondents said yes, but only red flag issues are raised during consultation (frailty, cognitive issues, heart disease, and significant comorbidity). The second question was: If you voted for a geriatric assessment in patients with mHSPC who are >= 75 years old, what do you recommend? 52% of respondents said G8/miniCOG/CGA or similar, and clinical assessment; 48% said clinical assessment only. The third question was: In daily clinical practice and outside of clinical trials, do you perform (not only recommend) geriatric assessments by validated instruments (ie. G8/miniCOG/CGA) in the majority of patients with mHSPC who are >= 75 years? 52% of respondents said yes; 48% of respondents said no.

Dr. Morgans also highlighted a 2020 systematic review she was senior author on looking at risk assessment and considerations for proper management of elderly men with advanced prostate cancer.³ Among 21 studies included, the benefits of treatment identified for systemic therapies commonly used to treat men with prostate in general extend to elderly patients. Evidence supports a multifaceted assessment of the risks of cancer and aging, and an understanding of the side effects of treatment to optimally guide therapeutic decision making for elderly patients.

Dr. Morgans then reviewed the key mHSPC trials, focusing on the subgroup analyses stratified by age. In the ARCHES trial of enzalutamide, there was a similar PFS benefit by age: <65 years HR 0.29, 95% CI 0.17 to 0.47; >=65 years of age HR 0.44, 95% CI 0.33 to 0.58.⁴ In the TITAN trial, generally there was an overall survival benefit for apalutamide regardless of age, although this was only statistically significant for men <65 years age (HR 0.56, 95% CI 0.33 to 0.94 vs 65-74 years of age HR 0.73, 95% CI 0.48 to 1.10 vs >=75 years of age HR 0.74, 95% CI 0.41 to 1.35).⁵ Additionally, in STAMPEDE Arm H assessing radiotherapy to the primary showing a survival benefit in low volume patients (HR 0.68, 95% CI 0.52 to 0.90), this may be a reasonable option in elderly men, given the somewhat low toxicity.⁶ Finally, Dr. Morgans highlighted one last question from the APCCC 2022 meeting: In frail patients (>= 75 years of age) with a life expectancy of >12 months with low-volume mHSPC, do you recommend radiation therapy of the primary tumor in addition to ADT? 52% of respondents said yes, in the majority of patients; 48% said yes, but only after a clinical re-assessment 3-6 months after start of ADT.

Dr. Morgans concluded her presentation with the following take-home messages:

• Frail and/or vulnerable older adult patients deserved risk-adapted treatment
• Remember that chronologic and biologic age are not the same; do not undertreat fit patients based on chronologic age
• We can use geriatric assessments to help identify areas of reversible decline to improve patients’ abilities to tolerate therapy
• Disease control outcomes and quality of life outcomes suggest similar benefits of systemic therapy for older and younger patients

Presented by: Alicia K. Morgans, Dana Farber Cancer Institute, Boston, MA

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.

References:

1. Droz JP, Albrand G, Gillessen S, et al. Management of prostate cancer in elderly patients: Recommendations of a task force of the International Society of Geriatric Oncology. Eur Urol. 2017 Oct;72(4):521-531.
2. Kenis C, Decoster L, Van Puyvelde K, et al. Performance of two geriatric screening tools in older patients with cancer. J Clin Oncol. 2014 Jan 1;32(1):19-26.
3. Shevach JW, Weiner AB, Kasimer RN, et al. Risk assessment and considerations for proper management of elderly men with advanced prostate cancer: A systematic review. Eur Urol Oncol. 2020 Aug;3(4):400-409.
4. Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy with Enzalutamide or Placebo in Men with Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019 Nov 10;37(32):2974-2986.
5. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med 2019 Jul 4;381(1):13-24.
6. Parker CC, James ND, Brawley CD, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): A randomized controlled phase 3 trial. Lancet 2018 Dec 1;392(10162):2353-2366.