(UroToday.com) The 2024 GU ASCO annual meeting featured a session examining the emerging evidence in localized and recurrent prostate cancer, including a presentation by Dr. Derya Tilki discussing biochemical recurrence after local treatment for prostate cancer.
Dr. Tilki started her presentation by reviewing the definitions of biochemical recurrence, which includes the RTOG-ASTRO Phoenix definition after radiotherapy as a rise of 2 ng/mL or more above the post radiation PSA nadir. After radical prostatectomy, the definition of biochemical recurrence is (i) NCCN: an undetectable PSA after surgery, with a subsequent detectable PSA that increases on 2 or more determinations or that increase to > 0.1 ng/mL, or (ii) EAU: the threshold that best predicts further metastasis is a PSA > 0.4 ng/mL and rising.
Biochemical recurrence after radical prostatectomy, as Dr. Tilki highlighted from her institution’s experience, is not infrequent as 20.3% of men in a sample of 14,532 patients experienced biochemical recurrence at a median follow-up of 50.8 months.1 Moreover, the risk of biochemical recurrence increases with increasing CAPRA-S score:
With regards to the natural history of biochemical recurrence, Dr. Tilki highlighted the classic JAMA paper by Dr. Pound, which was a retrospective review of 1,997 men who underwent radical prostatectomy between 1982 and 1997.2 Of these men, 315 (15%) developed biochemical PSA level elevation and 11 underwent early hormone therapy after the recurrence and were not included in the study. The 5-year metastatic progression free survival rate was 64% among 304 BCR patients who were observed until metastatic progression:
Dr. Tilki then discussed unpublished data from her institution that is looking at long-term oncological outcomes for patients with biochemical recurrence. Among 3,416 patients undergoing a radical prostatectomy (1992-2017) who experienced a biochemical recurrence (PSA >= 0.2 ng/mL), 5- and 10-year metastasis free survival is poorest with pT3 + Gleason 8-10 disease (66.6% and 52.5%, respectively) when compared to pT2 (92.1% and 82.7%, respectively), and pT3 + Gleason 7 disease (87.3% and 74.9%, respectively):
In a systematic review assessing the prognostic value of biochemical recurrence following treatment with curative intent, Van den Broeck et al. defined the EAU low-risk biochemical recurrence as a PSA-doubling time >1 year and pathologic ISUP grade <4 (whereby salvage treatment should be discussed but may not be needed), and EAU high-risk biochemical recurrence as a PSA-doubling time <= 1 year or pathological ISUP grade 4-5 (whereby salvage treatment is needed).3 As such, the EAU prostate cancer guidelines recommend stratifying biochemical recurrence patients into EAU low and high risk groups to stratify risk and allow appropriate treatment counseling.
Work from Dr. Tilki’s group externally validated the EAU biochemical recurrence risk groups in a publication in 2019.4 This study included 510 patients with EAU low-risk and 530 patients with EAU high risk biochemical recurrence among men that underwent radical prostatectomy between 1992 and 2006. The 5-year metastatic progression-free survival rates were significantly higher among patients with low biochemical recurrence risk compared to their high-risk counterparts. In multivariable analyses, the biochemical recurrence risk grouping reached independent predictor status for metastatic progression (HR 3.46; p<0.001):
Additionally, this study found that salvage radiation therapy, especially when delivered at a PSA <0.5ng/ml, was highly protective:
Dr. Tilki then highlighted the DIPPER clinical trial “Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy Outcomes.” Eligible patients will be those that (i) had a prior radical prostatectomy, and subsequently had an early biochemical recurrence (PSA 0.2 – 0.5 ng/mL), (ii) are stratified as EAU low risk, and (iii) have a negative PSMA PET/CT. These patients will then be randomized to Arm A (surveillance) versus Arm B (radiotherapy to the prostate bed +/- pelvic lymph nodes). The primary outcome for this trial is event free survival at 3 years:
With regards to adjuvant or early salvage radiotherapy, the ARTISTIC meta-analysis showed that there was no superiority of adjuvant radiotherapy compared to salvage radiotherapy based on event-free survival:5
Furthermore, presented at ESMO 2023, the RADICALS-RT trial showed that early salvage radiotherapy was as effective as adjuvant radiotherapy regarding overall survival. Finally, and to conclude her presentation, Dr. Tilki highlighted additional work from her group assessing the impact of adjuvant versus early salvage radiotherapy on all-cause mortality risk in men with adverse pathology defined as positive pelvic lymph nodes or pathologic Gleason score 8-10 prostate cancer and disease extending beyond the prostate (pT3/4). Over a median follow-up of 8.16 (IQR 6.00-12.10) years, among 26,118 men in this study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from prostate cancer. After excluding men with a persistent PSA, adjuvant compared with early salvage radiotherapy was associated with a significantly lower all-cause mortality risk among men with adverse pathology at radical prostatectomy when men with pN1 prostate cancer were excluded (HR 0.33, 95% CI 0.13-0.85; p = 0.02):
Presented by: Derya Tilki, MD, Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Jan 25 – Sat, Jan 27, 2024.
References:
- Tilki D, Mandel P, Schlomm T, et al. External validation of the CAPRA-S score to predict biochemical recurrence, metastasis, and mortality after radical prostatectomy in a European cohort. J Urol 2015;193(6):1970-1975.
- Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999 May 5;281(17):1591-1597.
- Van Den Broeck T, van den Bergh RCN, Arfi N, et al. Prognostic Value of Biochemical Recurrence Following Treatment with Curative Intent for Prostate Cancer: A Systematic Review. Eur Urol 2019 Jun;75(6):967-987.
- Tilki D, Preisser F, Graefen M, et al. External validation of the European Association of Urology Biochemical Recurrence Risk Groups to Predict Metastasis and Mortality After Radical Prostatectomy in European Cohort. Eur Urol. 2019 Jun;75(6):896-900.
- Vale CL, Fisher D, Kneebone A, et al. Adjuvant or early salvage radiotherapy for the treatment of localized and locally advanced prostate cancer: A prospectively planned systematic review and meta-analysis of aggregate data. Lancet 2020 Oct 31;396(10260):1422-1431.
- Tilki D, Chen MH, Wu J, et al. Adjuvant versus early salvage radiation therapy for men at high risk for recurrence following radical prostatectomy for prostate cancer and the risk of death. J Clin Oncol. 2021 Jul 10;39(20):2284-2293.