ASCO GU 2017: Challenging Cases in High-Risk, Recurrent, and Advanced Prostate Cancer (ARS) - Surgeon - Session Highlights
De novo oligometastatic hormone-sensitive disease
The patient is a 65-year old male who presented with a screening PSA of 7.58 ng/mL (from 4.2 ng/mL 2 years prior). He was asymptomatic, had a negative family history, and digital rectal examination demonstrated a firm prostate on the right. A prostate needle biopsy demonstrated Gleason 4+4= 8 disease in 8/15 cores, a right SV fragment positive for adenocarcinoma, and extensive intraductal carcinoma with cribriform architecture. Initially imaging studies were read as negative for systemic disease. The clinical stage was T3aN0M0. Questions were posed regarding the optimal management of this patient.
Dr. Chapin cited a meta-analysis (Petrelli et al. Clin GU Cancer, 2014) of multiple retrospective studies demonstrating improved prostate-cancer specific mortality for radical prostatectomy over radiotherapy (OR 0.56, 95% CI 0.37-0.85). The major limitations to these studies are selection biases associated with a retrospective review on intervention. A second point to consider is the role of therapy sequencing in multimodal therapy. Surgery can be curative in up to 50% of patients with high-risk prostate cancer. The sequence of surgery followed by post-operative radiation tends to be less toxic than radiation followed by surgery. Pathologic evaluation provides data for deciding on subsequent therapies. Lastly, multimodal therapy
Subsequent analysis of the staging studies demonstrated a positive bone scan lesion at the inferior left ramus with confirmation of a sclerotic focus in the same location on CT scan.
Dr. Chapin was asked about the role of PET scan in further staging these patients. He reiterated that PET scan is not a standard approach in this setting and cautioned that outcomes for primary therapy from the bone scan/CT scan era should not be extrapolated to PET findings outside the context of a clinical trial.
The bone biopsy was positive for metastatic adenocarcinoma. The patient was started on ADT. Dr. Chapin was asked about the role of local therapy in this setting?
There are two randomized controlled trials in this space. A phase II study is currently accruing that randomizes patients to best systemic therapy (BST) with local therapy versus BST alone. The primary outcome measure is overall survival. Secondary outcome measures include symptomatic local control, patient-reported outcomes (PROs), and quality of life (QOL). A number of correlative studies are planned to identify potential biomarkers. One hundred patients of a total one hundred twenty have been accrued. A phase III study is being designed through SWOG. It randomizes patients to standard systemic therapy with definitive treatment (surgery versus radiation) or standard systemic therapy alone. The primary outcome measure is overall survival. Secondary outcome measures are local progression and PRO/QOL outcome measures. Biomarker correlates are currently being worked out.
Recurrent disease after primary therapy
The patient is a 51-year old male who presented with a PSA of 5ng/mL. He underwent prostate needle biopsy which demonstrated Gleason 3+4=7 disease. The clinical stage was cT1cNXMX. He underwent a radical prostatectomy with no node dissection. Final pathology revealed Gleason 4+3=7, pT3aNxMx disease. The PSA was undetectable at the 6-week post op visit.
A question was posed regarding the use of adjuvant radiotherapy versus observation and the use of genomic classifiers in this setting. Dr. Chapin cautioned that none of the genomic classifiers have been evaluated in a prospective fashion. While the metastasis-free survival curves split favoring adjuvant radiotherapy over salvage radiotherapy in patients with high-risk genomic classifiers, one must keep in mind that the adjuvant group included all comers (i.e. some were not destined to recur) and the salvage group included only patients who recurred (thus inducing bias). Generally, Dr. Chapin leans towards a salvage radiotherapy approach.
The patient elected observation. At 6 months post-operatively, the PSA was detectable at 0.18ng/mL. What is the next step?
Dr. Chapin typically trends a few consecutive PSA levels. The definition of PSA failure after radical prostatectomy is > 0.2. He prefers starting salvage radiotherapy at PSA < 0.5ng/mL. In the absence of pelvic lymph node dissection, he would recommend full pelvic salvage radiotherapy with 6 months ADT.
PSA declined to 0.32, but then began to rise again. A left-sided pelvic lymph node was identified on C11-choline PET. Salvage left-sided pelvic node dissection performed. With regards to a salvage lymph node dissection, Dr. Chapin advised that there are typically multiple nodes involved and there is a need to extend the node dissection. In highly selected retrospective European data, there is some evidence for a benefit in approximately 15-20% of patients with a 3-year biochemical recurrence-free rate.
Speaker: Brian F. Chapin, MD, The University of Texas MD Anderson Cancer Center
Written By: Benjamin T. Ristau, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA