AUA 2019: Impact of Prostate Specific Antigen Doubling Time on Metastasis and Increased Costs Associated with Progression to Metastatic Castrate-resistant Prostate Cancer

Chicago, IL (Urotoday.com) Recent studies have suggested that Prostate-Specific Antigen Doubling Time (PSADT) is an important predictor of outcomes in non-metastatic castration-resistant prostate cancer (nmCRPC) patients. Until recently, there were no medications available for patients with nmCRPC until the reporting of PROSPER (enzalutamide)1 and SPARTAN (apalutamide)2 resulted in FDA approval of these medications with nmCRPC indication.  Even more recently ARAMIS reported similar findings for darolutamide3. Ahong Huang and colleagues presented results of their study evaluating the impact of PSADT on risk of metastasis, healthcare resource use and healthcare costs in nmCRPC patients.

This retrospective study was conducted on a sample of men aged >18 years from the Veterans Health Administration (VHA) database. nmCRPC patients were identified as those with medical or surgical castration and >2 PSA increases during active LHRH treatment between January 1, 2012, and December 31, 2016. The third PSA value >25% and 2 ng/ml higher than the first PSA value was designated as the CRPC date (index date). Patients had continuous VHA enrollment for >12-months pre-and post-index date and were followed until the first occurrence of death or disenrollment. Post-index PSA values were used to calculate PSADT and patients were grouped into 2-month cohorts. Cox regression model assessed the impact of PSADT on metastasis and healthcare resource use and costs per patient per month (PPPM) were evaluated among cohorts.

The flow chart for this study is as follows:

AUA 2109 fig 1 flow chart

Among the study cohort of 3,579 nmCRPC patients (mean age = 73 years), there were 1,389 that progressed to mCRPC. Overall, patients had comorbid hypertension (73.0%), hyperlipidemia (58.0%), and type II diabetes (33.3%). Of the 2800 patients with evaluable PSA, the median PSADT was 17 months after a median follow-up of 27 months. Relative to the PSADT >12 months cohort, PSADT <2 (HR 33.77, CI 25.93-43.96), 2-4 (HR 14.32, CI 11.83-17.32), 4-6 (HR 6.58, CI 5.42-7.98), 6-8 (HR 4.14, CI 3.27-5.25), and 8-10 (HR 3.14, CI 2.45-4.03) months cohorts were associated with higher risk of metastasis.

AUA 2019 adjusted hazard ratios

PSADT <2, 2-4, 4-6 months cohorts had higher mean all-cause inpatient stays (0.08, p < 0.0001; 0.05, p < 0.0001; 0.04, p=.0002) and outpatient visits (3.03, 2.59, 2.40, all p < 0.0001), higher mean PC-related inpatient stays (0.07, 0.03, 0.02, all p < 0.0001) and outpatient visits PPPM (1.11, 0.89, 0.73, all p < 0.0001) than PSADT >12 months cohort. PSADT <2, 2-4, 4-6 months cohorts incurred significantly higher all-cause total costs ($6,162, $4,436, $3,767; all p < 0.0001)

AUA 2019 all cause costs

and higher prostate cancer-related total costs PPPM ($4,248, $2,830, $2,220; all p < 0.0001).

AUA 2019 PC related costs

The strength of this study is its generalizability, given that data was derived from the equal access Veterans Affairs database. PSADT is a powerful predictor of future metastases risk, and each acceleration of PSADT by 2 months is associated with increased risk of metastases; at PSADTs < 6 months, the economic burden increases sharply. These are important metrics and highlight the need for appropriately identifying high-risk nmCRPC patients that may derive a therapeutic and economic benefit by delaying mCRPC.

Speaker: Ahong Huang, STATinMED Research/SIMR, Inc., Plano, Texas

Written By: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia, @zklaassen_md at American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois

References:
1. Hussain M, Fizazi K, Saad F, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474.
2. Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378(15):1408-1418.
3. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2019 Feb 14 [Epub ahead of print].