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AUA 2019

AUA 2019: Three Papers in the Past Year that Influenced my Practice in Prostate Cancer

Chicago, IL (UroToday.com) Dr. Brian Chapin presented three papers that changed his practice for prostate cancer in the past year. The first paper was by Salami et al.1 “Transcriptomic heterogeneity in multifocal prostate cancer” published in JCI Insight. The clinical need for this study is twofold: i) Identify under sampled high-grade components of the same tumor focus, and ii) Identify an unsampled, spatially and genomically distinct, high-grade tumor missed on the biopsy.

The objective was to interrogate and compare commercially available prognostic transcriptomic signatures in clinically relevant multifocal prostate cancer. The author’s hypothesis was associated with histology of the sampled tissue and not able to identify concomitant multi-focal high-grade tumors. An RT-PCR based RNA sequencing assay was used to interrogate and compare commercially available prognostic transcriptomic signatures in 120 primary prostate cancer samples (44 patients). The focus of the evaluation was to compare GG1 only (n=8) vs GG1 in the presence of GG2-5 (n=21), and multifocal cases comparing GG1 (n=21) to GG4/5 (n=34). Derived expression scores were positively correlated with tumor grade (all p < 0.001), both within the same case and across the entire cohort. In cases of extreme grade-discordant multifocality (co-occurrence of GG1 and ≥GG4 foci], gene expression scores were significantly lower in low-(GG1) versus high-grade (≥GG4) foci (all p < 0.001). No significant differences in expression scores, however, were observed between GG1 foci from prostates with and without coexisting higher grade cancer. These authors concluded that derived commercially available prognostic signatures obtained from low grade cancer foci do not predict for co-existing high-grade foci. Dr. Chapin states that this paper changed his practice in that he rarely ordered genomic tests for his low-grade patients before and he questions the practice even more now. He notes that the remaining question is “Can we overcome sampling error?”

The second paper was by Touijer et al. “Survival outcomes of men with lymph node positive prostate cancer after radical prostatectomy: A comparative analysis of different postoperative management strategies” published in European Urology2. The clinical need for this study is to identify best management strategies for post-radical prostatectomy pN+ patients. The objective of the study was to evaluate the association between three different management strategies and survival in pN+ prostate cancer. There were three institutions involved in this study (MSKCC, Mayo Clinic and San Raffaele), including 1,388 pathologic node positive prostate cancer patients post-radical prostatectomy. The three approaches to treatment included (i) observation (28%), (ii) lifelong ADT (49%) and (iii) adjuvant ADT + EBRT (prostate fossa + whole pelvis; 23%). ADT + EBRT was associated with better OS than ADT alone (HR 0.46, 95%CI 0.32-0.66) or observation (HR 0.41, 95%CI 0.27-0.64). Higher-risk patients benefited more from ADT + EBRT than lower-risk patients. Adjuvant ADT + EBRT was also associated with better CSS than observation or ADT alone (p<0.0001); ADT had better CSS compared to observation (HR 0.64, 95%CI 0.43-0.95). However, ADT was associated with an increased risk of other-cause mortality (HR 3.05, 95% CI 1.45-6.40) compared with observation, resulting in similar OS between ADT and observation (HR 0.90, 95%CI 0.65-1.25). The authors concluded that in men with lymph node metastases adjuvant ADT + EBRT confers a survival advantage over observation of lifelong ADT alone. Dr. Chapin say that this has changed his practice in that he has increased his use of ADT/EBRT in pN+ patients. Questions that remain include: Is a randomized trial realistic? He notes that several ongoing studies (FORMULA-509 and GU008) have radiation therapy in both arms. 

The third paper was by Palma et al. “Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): A randomized, phase 2, open-label trial” published in Lancet3. The clinical need for this paper is that we do not know if metastasis directed therapy incurs an oncologic advantage in metastatic cancer. The objective of this study was to assess standard of care palliative treatments with or without stereotactic ablative radiotherapy (SABR) in up to 5 metastatic lesions. The author’s hypothesis was that patients with oligometastatic disease will have improved outcomes with treatment of their metastatic sites. This study included any cancer (primarily breast, prostate, colorectal, and lung) who were then randomized 1:2 to standard of care vs standard of care + SABR. Standard of care was at the discretion of the physician and the primary endpoint was OS. There were 99 patients at 10 centers and median follow-up was 25.5 months. Median OS was 28 months (95%CI 19-33) in the control group versus 41 months (26-not reached) in the SABR group (HR 0.57, 95%CI 0.30-1.10; p =0.090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0.026), an absolute increase of 20% (95%CI 5-34). Treatment-related deaths occurred in three (4.5%) of 66 patients after SABR, compared with none in the control group. The authors concluded that SABR was associated with a 13-month increase in OS and doubling of PFS. Dr. Chapin notes that with regards to changes to his practice, he is skeptical and notes that we should be enrolling patients in randomized studies for metastasis directed therapy; he has reduced use outside of a trial in an attempt to balance risk of toxicity. 

Presented by: Brian Chapin, MD Anderson Cancer Center, Houston, TX

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. Salami SS, Hovelson DH, Kaplan JB, et al. Transcriptomic heterogeneity in multifocal prostate cancer. JCI Insight 2018 Nov 2;3(21). Pii:123468.
  2. Touijer KA, Karnes RJ, Passoni N, et al. Survival outcomes of men with lymph node positive prostate cancer after radical prostatectomy: A comparative analysis of different postoperative management strategies. Eur Urol 2018 Jun;73(6):890-896.
  3. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): A randomized, phase 2, open-label trial. Lancet 2019 Apr 10 [Epub ahead of print].