Dr. Tran began with presenting two cases. The first case was a 66 y/o male with cT2cN1M0, Gleason 5+4 (12 out of 12 cores positive), PSA 14 ng/mL who subsequently received 80 Gy of IMRT and long-term androgen deprivation. His PSA did nadir to 0.7 ng/mL and subsequently at two years rose to 5.4 ng/mL with castrate-level testosterone. Imaging demonstrated a bulky 2.5 cm left para-aortic and retroperitoneal lymphadenopathy. Based on guidelines, first line treatment for this patient would likely be Sipuleucel-T.
The second case was a 72 y/o man with TxN0M0R1 Gleason 4+4 disease, PSA 7 ng/mL who underwent a radical prostatectomy in the 1990s and subsequently had biochemical recurrence with salvage radiotherapy and complete response. He then had a rising PSA treated with ADT for many years until castration resistance, at which point he was treated with docetaxel, abiraterone, and cabazitaxel resulting in a PSA of 1.3 ng/mL and stable disease with a right adrenal metastasis. With two years of observation and treatment with ADT alone, the PSA rose to 79 ng/mL and the adrenal metastasis increased to 3.9 cm. In this situation, the guidelines would suggest a reasonable option would be for treatment with enzalutamide.
Dr. Tran notes that if oligoprogression is a pathway to widely metastatic disease, then stererotactic body radiation therapy (SBRT) may potentially alter the natural history of the disease. SBRT is highly focused radiation concentrated on tumors, with low doses to the surrounding tissues. This may be delivered in single or hypofractionated treatments and provides very precise delivery with image guidance, immobilization and other technologies to ensure accuracy. Dr. Tran points out that there is decent surgical data for treating oligometastatic disease in other disease sites, namely colorectal patients with metastases to the liver and/or lung. The SBRT oligometastatic treatment data, although less mature, suggests that local control rates are >80-90%, survival rates are comparable to surgical series, there is minimal toxicity, treatment is possible for disease in previously irradiated sites, and early series with respect to prostate cancer suggest acceptable local control and disease-free survival.
Dr. Tran then highlighted that prostate cancer has intrinsic/acquired resistance with continued systemic therapy. Specifically, if there is progression of a limited number of metastatic deposits, while all other metastases are controlled with systemic therapy. Thus, the hypothesis is that if widely metastatic disease is representative of oligoprogression, then local ablative therapies can theoretically alter the natural history.
Referring back to the two cases presented at the beginning of his talk, Dr. Tran notes that for case #1, treatment of the retroperitoneal bulky nodes with 5.6 Gy SBRT x5 QOD resulted in PSA nadir to 0.14 with decrease in node side to 0.5 cm. For case #2, treatment with 10 Gy SBRT x 5 QOD and continued treatment with ADT alone resulted in a PSA nadir to <0.1 ng/mL with decrease in the adrenal metastases to 3cm. In their cohort of men at Johns Hopkins, Dr. Tran notes that 65% of oligometastatic men had a >50% PSA response and a median time to next intervention of 10 months. In conclusion, Dr. Tran notes that SBRT for treatment of oligometastatic prostate cancer is an emerging field, with PSA responses to SBRT and delay in time to next treatment.
Presented by: Phuoc T. Tran, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA