Washington, DC (UroToday.com) In the first prostate cancer session at the 2019 Society for Urologic Oncology meeting in Washington, DC, Dr. Matthew Cooperberg highlighted the similarities between breast cancer and prostate cancer and suggested some lessons that urologic oncologists can draw from the evolution of breast cancer treatment. He credited his colleague at UCSF, Dr. Laura Esserman, for her leadership in breast cancer research and her assistance with the preparation of his talk.
Breast cancer and prostate cancer are the most prevalent malignancies in women and men respectively comprising 30% and 20% of malignancies in their respective gender. Both of these cancers have significant associated mortality, comprising 15% and 10% of cancer deaths, making them the 2nd highest cause of cancer mortality in women and men after lung cancer. At the same time, the percentage of cancers that are ultimately lethal in each disease is low and the morbidity associated with disease treatment can be high, leading to a significant risk of overtreatment. Finally, screening for each disease has greatly increased their detected incidence, but the value of this screening in increasing overall survival has been questioned.
On a biologic level, Dr. Cooperberg also highlighted emerging data suggesting that the luminal A, luminal B, and basal genomic subtypes that have been recognized in breast and other cancers are also present in prostate cancer and are predictive of outcomes of therapy.1,2 The dream, he imagines, is that one day a tumor's genetics may be more useful in determining its treatment than its organ of origin.
Dr. Cooperberg did make a point of highlighting one important difference between the two diseases. Namely, while the advent of PSA screening was associated with a marked decrease in the incidence of de novo metastatic prostate cancer, there was no such association with the onset of the mammographic screening era.
The remainder of the talk focused on three ongoing trials in breast cancer that may have applicability to prostate cancer.
In the WISDOM trial, women are randomized to routine annual screening vs personalized risk-based screening. Validated risk factors including exposures/lifestyle, breast density, 9 known breast cancer genes, and a SNP-based polygenic risk score are used to determine the age for screening initiation/cessation, screening frequency, and screening modality. Dr. Cooperberg pointed out that this type of design may be even more practical for prostate cancer as baseline PSA could be used to replace genetic testing as a relatively strong lab-based risk-prediction tool. Interestingly, in this pragmatic trial, women who declined to be randomized could still consent to have their data and tissue collected prospectively.
In the TailoRX trial,3 women undergoing surgical treatment for breast cancer were risk stratified using a combination of clinical features and a 21-gene classifier of recurrence risk. Those with low recurrence risk scores received adjuvant endocrine therapy alone, those with high scores received adjuvant chemoendocrine therapy, and those with intermediate scores were randomized to one of the two adjuvant therapies. Noninferiority of endocrine therapy alone was demonstrated in the intermediate cohort, although there was some benefit noted in the group of women with age <50 and recurrence risk score 16-21. The parallel with genetic scores such as Decipher and the decision to administer adjuvant radiotherapy after prostatectomy are clear, although with the recent presentation of RADICALS-RT, RAVES, GETUG-AFU 17, and the ARTISTIC meta-analysis the question is more likely to be the fine-tuning of early salvage therapy rather than true adjuvant therapy.
Finally, in the I-SPY trial, patients with breast cancer first undergo a core biopsy to assess eligibility. Eligibility is determined based on the MammaPrint array as well as receptor positivity. Those deemed eligible are treated with Paclitaxel plus one of several new drugs followed by surgery. The endpoints in this trial are the pathologic responses seen in surgical specimens. This allows for rapid iteration to assess the effectiveness of new therapies against the primary tumor with the option to add new drugs and schedules over time. The prospect of this type of trial design in prostate cancer is all the more interesting in light of the prognostic value of the finding of complete pathologic response or “minimal residual disease” on prostatectomy specimens after neoadjuvant therapy discussed by Dr. Adam Kibel and Dr. Martin Gleave later in this session.
Presented by: Matthew R Cooperberg, MD, MPH, FACS, Department of Urology, University of California, San Francisco, San Francisco, California, USA.
Written by: Marshall Strother, MD, Society for Urologic Oncology Fellow, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA @mcstroth at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DCReferences:
- Zhao SG, Chen WS, Das R, et al. Clinical and Genomic Implications of Luminal and Basal Subtypes Across Carcinomas. Clin Cancer Res. 2019;25(8):2450-2457.
- Zhao SG, Chang SL, Erho N, et al. Associations of Luminal and Basal Subtyping of Prostate Cancer With Prognosis and Response to Androgen Deprivation Therapy. JAMA Oncol. 2017;3(12):1663-1672.
- Sparano JA, Gray RJ, Makower DF, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. 2018;379(2):111-121.