1. Goodwin, Peter M.

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MUNICH-Radiotherapy (RT) directed to the prostate improved survival in men who had newly diagnosed prostate cancer with "lower metastatic burden" in the STAMPEDE study reported to the 2018 ESMO Annual Congress.

Chris Parker, MD, MR... - Click to enlarge in new windowChris Parker, MD, MRCP, FRCR. Chris Parker, MD, MRCP, FRCR

Study author Chris Parker, MD, MRCP, FRCR, a clinical oncologist at the Institute of Cancer Research and the Royal Marsden Hospital in Sutton, U.K., told the conference that, while prostate RT had not improved survival in all of the men in the study, it had improved survival in the subset who had lower metastatic burden-those with fewer than four bone metastases and no visceral disease.


"So, going forward, prostate radiotherapy should now be a standard treatment option for men with newly diagnosed metastatic prostate cancer with a low metastatic burden," he said.


The STAMPEDE finding implied that prostate RT was also recommended for men without any distant metastatic disease who had regional nodal metastases-even though this subgroup of patients had not been included in the analysis of the STAMPEDE trial.


"If prostate radiotherapy improves survival for men with distant metastases, we can be very confident that it would improve survival for men with regional nodal disease," Parker said.


Most men in this group had currently been receiving drug treatment alone, but this needed to change. "Going forward, prostate radiotherapy should be a standard treatment for these men as well."


He also suggested that the principle of irradiating primary tumors to achieve off-target "abscopal" effects among patients with oligometastases should be studied in other malignancies, too.


Parker said the study had been done to find out if the standard approach using drugs only for all patients newly diagnosed with metastatic prostate cancer had been optimal. Conventionally, it had been thought that when the cancer had already spread there would have been no point in treating the prostate itself (with surgery or RT) since it would have been too late-tantamount to "shutting the stable door after the horse had bolted," he said.


But Parker noted that in animal models of metastatic cancer, it had been shown that when the primary tumor had been treated any metastases "slowed down" and the animals lived longer. "So we wanted to ask the question: Is the same thing true for men with metastatic prostate cancer in the clinic?"


In particular, the researchers hypothesized that, if there had been a benefit from treating the prostate, it was likely to have been greater in men who had low metastatic burden rather than having many metastases.


Study Details

A total of 2,061 patients (median age 68 years) from the U.K. and Switzerland who were newly diagnosed with metastatic prostate cancer were randomized either to receive standard of care (SOC) drug treatment (consisting of lifelong androgen deprivation therapy with early docetaxel permitted from 2016) or SOC drug treatment plus prostate radiotherapy. The primary outcome measure (OM) was death from any cause. Failure-free survival (FFS) was a secondary OM.


In all patients taken together, prostate RT improved FFS with a hazard ratio (HR) of 0.76. But it did not improve overall survival. However, the pre-specified subgroup analysis found improved OS for prostate RT in 819 men with lower metastatic burden (with a HR of 0.68-equivalent to OS lengthening by just over one-third), but not in the 1,120 men who had higher metastatic burden (defined as four or more bone metastases with at least one of these outside the axial skeleton and/or visceral metastases). "The hazard ratio was highly significant statistically," said Parker.


He described RT as "well-tolerated" and said it was a simple treatment that was widely available in cancer centers throughout the world. In the study, 5 percent of patients had grade 3-4 adverse events during treatment and 4 percent after treatment.


"There was a small increase in risk of bladder and bowel side effects, but these were modest," Parker noted. "The side effects are certainly outweighed by the survival benefit."


Survival at 3 years was up from 73 to 81 percent, said Parker. "So the absolute benefit is 8 percent."



Karim Fizazi, MD, PhD, from the Gustave Roussy Institute and University of Paris-Sud in France, said this had been the first evidence that treating the local primary tumor was associated with improvement in overall survival in men with metastatic prostate cancer and minimal disseminated disease, and that the finding of no significant increase in overall survival in men with higher burden of disease was in line with previous data.


"For men with newly diagnosed oligometastatic prostate cancer, it is quite likely that this is practice-changing," Fizazi noted. "For men with higher burden of disease, more data are needed regarding whether upfront local treatment improves or prevents local symptoms-which by itself may justify its use in the absence of an overall survival benefit."


Fizazi explained that, although the study had been a large randomized phase III trial, only 18 percent of the patients had received early docetaxel and none had received early abiraterone-although these treatments are now part of the standard regimen in fit men.


Ignacio Duran, MD, PhD, a medical oncologist treating genitourinary cancers from the Marques de Valdecilla University Hospital in Santander, Spain, chaired a press briefing to announce the STAMPEDE findings at ESMO where he said the result opened the door to apply a new treatment "that may have an impact in the life of these patients."


"This is a change of paradigm," Duran stated. "This is a practice-changing study. So, we've got to go back home-thinking we need to sit down and talk to our radiation oncologists because we're going to start giving radiation to patients with metastatic disease. We're going to start treating their prostates." He sought to raise awareness among doctors that, in patients with newly diagnosed prostate cancer with low burden metastatic disease, treating the prostate with radiation really made a difference.

Ignacio Duran, MD, P... - Click to enlarge in new windowIgnacio Duran, MD, PhD. Ignacio Duran, MD, PhD

Peter M. Goodwin is a contributing writer.