1. Goodwin, Peter M.

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The biggest randomized study of treatment for PSA-detected prostate cancer has confirmed that for most patients radical prostatectomy and radiotherapy did not reduce prostate-specific or overall mortality as compared with "active monitoring." And, overall, PSA-detected prostate cancer killed very rarely. However, active treatment reduced the spread of the disease.

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Two papers from Oxford and Bristol Universities in the U.K. report the first analysis-at a median of 10 years-from the Prostate Testing for Cancer and Treatment (ProtecT) trial published on line in the New England Journal of Medicine (DOI: 10.1056/NEJMoa1606220).


Low Mortality

"Mortality from prostate cancer was extremely low-at approximately 1 percent-irrespective of the treatment allocated to these patients," said lead author Freddie C. Hamdy MBChB, MD, FRCS, Nuffield Professor of Surgery and Professor of Urology at the University of Oxford. He said mortality was lower than expected and that both surgery and radiotherapy reduced the spread of localized prostate cancer.


"Receiving treatment reduces the incidence of metastasis and clinical progression by approximately half compared to active monitoring," he told Oncology Times. All because mortality was unaffected by the choice of initial treatment.


"The next good news is that active monitoring certainly seems to be a good and safe option for men," he said, adding that by opting for active monitoring patients reduced or avoided side effects from treatment. "But we still do not know exactly which cancers are lethal," he warned.



"PSA [testing] has allowed a very large number of men with early small-volume, small-risk prostate cancer to be detected, and that has led to overdetection [and] overtreatment [in] men who otherwise would not have progressed to lethal consequences," Hamdy said. But he also added there had been "under-treatment" of the disease because the lethal forms were not being recognized.


The ProtecT study investigated the effectiveness and quality of life with the three most common treatments for localized clinically detected prostate cancer-active monitoring, radical prostatectomy, and radiotherapy. (The expression "active monitoring" was carefully chosen because it conveyed the clinicians' readiness to treat with other techniques in case of need-which eventually happened in about half of all patients in this surveillance group.)


From almost 200,000 men invited for PSA screening, around 100,000 responded, 82,429 were tested, and 2,664 cancers were detected. The men who had clinically localized disease were invited to enroll in the study to be treated with one of the initial treatment options.


The 1,643 patients who agreed to be randomized were divided into three groups-545 had active monitoring, 553 surgery, and 545 radiotherapy. After their initial treatment, they were followed-up for a median of 10 years. The primary endpoint was disease-specific mortality and secondary endpoints were all cause mortality, patient-reported outcomes, disease progression, and development of metastases.


Hamdy noted the findings were unexpected, very interesting, and conveyed "really important" messages. "The survival is extremely high-99 percent," he said, and he added that none of these treatments made any difference to mortality. "So irrespective of the treatment allocated, there were no differences in disease-specific mortality," he said.


Disease Spread

"At an average of 10 years, approximately 80 percent of men in the active monitoring arm did not show any sign of progression," he said. But he added the study clearly showed that, in the radiotherapy and surgery arms, treating the disease early halved the number of men whose disease metastasized or had clinical local progression.


It was still not clear whether reducing the spread of localized prostate cancer-at the cost of side effects from the active treatments-could impact patient outcomes beyond 10 years. Hamdy said it was not clear whether the differences could eventually translate into benefits in survival. "We do not know because we have insufficient events," he said.


ProtecT had brought good news for patients, he repeated, since it had revealed that if they had clinically localized disease the risk of dying from the cancer-irrespective of treatment-was "very, very, low."


The second analysis from ProtecT published in the New England Journal of Medicine under the lead authorship of Jenny Donovan, OBE, FMedSci, PhD, Professor of Social and Community Medicine at the University of Bristol (DOI: 10.1056/NEJMoa1606221) documented the side effects and looked at how patients felt about receiving each of the three initial treatments.


"This is absolutely critical because up until now we had insufficient information about the short-, medium- and long term outcomes of giving all these treatments," Hamdy said. He regarded this as "really important" because patients could now weigh the benefits and drawbacks of each treatment in the light of hard data on their likely survival. "It's going to allow a patient to know what the likely consequences of these treatments are on quality of life, sexual life anxiety status, continence," he noted.


When he was asked for his latest recommendations to clinicians, he said patients needed to have the data. "Give them the right information so that they're able to make an informed choice about how they are going to decide what treatment they would like for themselves," he said. But he emphasized that patients had no need to panic and should "not to rush into making these decisions.


And he pointed out that active monitoring was a completely valid option for many men who are diagnosed with PSA-detected prostate cancer. "The active monitoring program allows them to avoid the side effects of treatment," he said.


In an accompanying comment in the New England Journal of Medicine, Anthony V. D'Amico, MD, PhD, Chief of Genitourinary Radiation Oncology at Brigham and Women's Hospital and the Dana-Farber Cancer Institute in Boston, as well as Professor of Radiation Oncology, Harvard Medical School, wrote that the "best" initial approach to low-risk and intermediate-risk prostate cancer remained unknown. He agreed about the need for longer-term results. But he wrote that men could select a treatment using the data on health-related quality of life without fear of possibly selecting a less effective cancer therapy.


Peter M. Goodwin is a contributing writer.