(UroToday.com) In an educational session of the American Society for Radiation Oncology (ASTRO) Annual Congress focussing on Multidisciplinary Management of Very High Risk Prostate Cancer, Dr. Sarah Psutka presented on the role of surgery for these patients.
Dr. Psutka began by highlighting the NCCN clinical practice guidelines in oncology which emphasize that surgery may be considered appropriate initial therapy for patients with high-risk, very-high risk, or N1 disease in patients who have anticipated survival of at least 5 years or are symptomatic. However, it is not indicated for patients with M1 disease, even in those with low volume metastasis.
She then discussed four different surgical considerations in patients with high-risk and metastatic prostate cancer, including primary radical prostatectomy in high-risk disease, cytoreductive prostatectomy in patients with de novo metastatic prostate cancer, salvage lymph node dissection, and surgical metastasis directed therapy.
Addressing the first of these, the role for radical prostatectomy in high-risk prostate cancer, she highlighted recent data published by Dr. Kishan and colleagues in JAMA Network Open examining a multicenter cohort of 6004 men treated with radical prostatectomy, external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT), or EBRT + brachytherapy boost + ADT. When employed in an “optimal” manner, the authors found equivalent cancer specific morality outcomes, though metastasis free survival rates were highest in the EBRT + brachytherapy boost + ADT arm. However, the key takeaway from this paper was that multimodal therapy was critical to outcomes for these patients.
In the context of metastatic prostate cancer, Dr. Psutka then described the rationale for surgery, including a symptomatic benefit both in terms of symptoms that may be present at diagnosis and the avoidance of future symptomatic progression, as well as the potential to alter systemic tumor biology, remove cancer cell populations that may be resistant to systemic therapy, and potentially decrease the need for systemic therapy. When considering the role of surgery in metastatic prostate cancer, it is key to consider the shifting disease landscape as a result of advanced imaging: biologically, there exists a continuum between truly localized high risk disease and frankly widespread metastatic disease. The quality of our imaging approaches can vary where patients sit on this spectrum. Thus, in the early, low-volume oligometastatic disease space, there may exist a window of opportunity for cure.
Dr. Psutka emphasized that the recent proPSMA trial has shown that when imaged with 68Ga-PSMA PET-CT, a substantially higher proportion of patients with high-risk disease will be found to have pelvic nodal or distant metastases. Historically, based on conventional imaging, many of these patients would have been characterised as having localized disease. Thus, how we should now categorize and treat these patients is somewhat uncertain.
Further, she highlighted that there is variability in the definition of oligometastatic disease, included in large randomized controlled trials.
However, there is evidence that curative intent metastasis directed therapy may be feasible and offer meaningful clinical responses.
Moving to the question of cytoreductive prostatectomy, a multi-institutional cohort of 106 patients showed that this is a safe approach with complication rates similar to surgery for localized high-risk disease. However, other studies have reported the potential for serious harm including a 6% rate of major complications at 90 days, including one death. Perhaps more notably, in the multi-institutional cohort, more than half of patients had positive surgical margins.
However, a number of observational studies, ranging from prospective cohorts to large population-based studies, have shown a potential benefit both in terms of overall and cancer-specific survival. However, the important influence of selection biases cannot be addressed in these data. What is clear however is that patients who receive surgery are much less likely (7%) to have locoregional complications of prostate cancer as compared to those who receive best systemic therapy alone (35%; p<0.001). These complications include ureteral or urinary retention, hematuria, and others.
She further highlighted that a number of factors may influence decision-making regarding the role of surgery in patients with advanced prostate cancer, including disease burden, the synchronicity of metastasis, tumor related symptoms, and patient factors. However, optimal patient selection remains to be determined. She emphasized that uro-oncologists must be transparent regarding the limitations of the available data, the risks of intervention, the unknown potential outcomes, and the role of clinical trials. Currently, there are many ongoing trials that are seeking to better define the role of surgery in metastatic prostate cancer.
These studies have a variety of outcomes, which then are reflected in methodology and sample size. Importantly, many are considering patient-reported quality of life metrics. However, the SWOG 1802 study (which does not include quality of life metrics) is the largest and perhaps best known of these studies.
Presented by: Sarah Psutka, MD, Assistant Professor, Urology, University of Washington School of Medicine
Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting, Sat, Oct 23 – Wed, Oct 27, 2021.