(UroToday.com) As a portion of the European Society for Medical Oncology (ESMO) Annual Congress, an Educational Session focused on the management of patients with node-positive locally advanced prostate cancer was held. In this context, Dr. Chris Parker discussed the role of radiotherapy for these patients. He began by emphasizing that there are no randomized controlled trials testing the role of radiotherapy in this disease setting.
Dr. Parker began with a summary of observational studies in patients with node-positive disease. He began by citing data from Dr. Lin and colleagues assessing the role of radiotherapy with or without radiotherapy in patients with clinically node-positive disease. Relying on more than 600 patients, a large difference in overall survival was noted. However, he noted this to be “poor evidence” as a result of many factors, including that the survival difference emerges very early, a fact he deems unable to be attributable to prostate cancer or its treatment. Instead, this likely reflects selection bias. However, somewhat better evidence may be derived from the STAMPEDE cohort. In a paper published in JAMA Oncology, the STAMPEDE investigators significantly longer failure-free survival among patients with node-positive locally advanced prostate cancer who received radiotherapy compared to no radiotherapy. This however wasn’t a randomized comparison.
The use of the biochemical control outcome is somewhat more convincing that this may be due to a cancer related effect. However, he highlighted prior work demonstrating that observational studies often correlate poorly with randomized controlled trials of the same question in oncology.
Dr. Parker then moved to discuss randomized controlled trials of radiotherapy versus no radiotherapy in similar clinical scenarios. He first discussed the historical MRC PR02 trial of radiotherapy versus orchiectomy versus the combination in patients with locally advanced disease. This study showed no difference and led to the initial belief that radiotherapy was ineffective in this disease space. Subsequently, the MRC PR2 / NCIC PR07 trial assessed the combination of androgen deprivation and radiotherapy versus androgen deprivation along in patients with locally advanced disease. Notably, these patients were had N0/Nx disease though only 8% had nodal imaging. Thus, many probably had node-positive disease which would have been detected with appropriate imaging. Patients received, by current standards, relatively low dose radiotherapy. Further, approximately 72% had pelvic nodal radiotherapy. In spite of this, the trial showed a significant improvement in the risk of death from prostate cancer for the addition of radiotherapy (HR 0.46, 95% CI 0.34-0.61). Further, this also translated to an overall survival benefit.
Subsequently, Dr. Parker discussed the SPCG-7 trial which acts as a confirmatory study, assessing the same study question. Again, no pelvic imaging was mandated though patients had nodal sampling if PSA was greater than 11 ng/mL. In this case, patients only received prostate-directed radiotherapy, in addition to androgen deprivation. Again, this trial demonstrated a survival benefit to the addition of radiotherapy to androgen deprivation, with a prostate cancer survival benefit and an overall survival benefit.
Finally, Dr. Parker discussed the STAMPEDE trial analysis examining the question of radiotherapy to the primary tumor in the setting of metastatic disease. These patients were randomized to receive prostate-directed radiotherapy or not, in addition to systemic therapy. This demonstrated an overall survival benefit among those with low metastatic burden. While many have criticized this finding on the basis that it is predicated among a subgroup analysis, Dr. Parker pointed out that this finding meets the criteria for the believability of subgroup effects.
Finally, Dr. Parker circled back to the question of the role of radiotherapy in patients with node positive disease. He suggested that node positive disease lies on a spectrum between node-negative locally advanced disease and low-volume metastatic disease. Thus, given the similar findings from SPCG-7 and STAMPEDE, he inferred that we may expect a similar effect to the use of radiotherapy in this disease indication.
He said that he is confident that if such a trial was performed, it would show an overall survival benefit but then emphasized that he doesn’t believe such a trial will be performed as he deems it unethical to randomize patients to receive androgen deprivation alone.
Moving on, he raised the question of whether radiotherapy alone or surgery followed by radiotherapy (if necessary) is a preferable local treatment strategy. Again, there are no randomized data to guide our decision-making. He emphasized that, compared to the provision of post-operative radiotherapy, primary radiotherapy may have a smaller treatment volume with higher doses delivered. Thus, at least the radiotherapy component of local treatment can be more optimally delivered in the primary setting.
Further, he used mapping data from a study of 68-Ga-PSMA among patients with recurrent disease following radical prostatectomy, emphasizing that the distribution of recurrent disease is highly variable.