Ten-Year Follow-up in the ProtecT Trial

Posted by • October 13th, 2016


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The management of clinically localized prostate cancer that is detected on the basis of prostate-specific antigen (PSA) levels remains controversial. The National Institute for Health Research–supported Prostate Testing for Cancer and Treatment (ProtecT) trial was designed to evaluate the effectiveness of the three major contemporary treatment approaches to reducing prostate-cancer mortality and improving clinical outcomes in men with PSA-detected clinically localized disease. Hamdy et al. reported the effectiveness of each intervention in relation to prostate-cancer–specific mortality and all-cause mortality and the incidence of metastases and disease progression at a median of 10 years of follow-up in the randomized trial. In the ProtecT trial, over 1600 men with PSA-detected localized prostate cancer were assigned to active monitoring, prostatectomy, or radiotherapy. Although more patients assigned to active monitoring had disease progression, overall survival was similar in the three groups in a new Original Article.

Clinical Pearl

• Why is the management of clinically localized prostate cancer that has been detected with PSA testing controversial?

In the United States alone, an estimated 180,890 cases will be diagnosed in 2016, and 26,120 men will die from the disease. The widespread use of PSA testing has resulted in a dramatic increase in the diagnosis and treatment of prostate cancer, but many men do not benefit from intervention because the disease is either indolent or disseminated at diagnosis. Prostate cancer often progresses slowly, and many men die of competing causes. In addition, interventions for prostate cancer can have adverse effects on sexual, urinary, or bowel function.

Clinical Pearl

Are there prostate-cancer mortality differences between prostatectomy, radiotherapy, and active monitoring in men with PSA-detected clinically localized disease?

At a median follow-up of 10 years, the ProtecT trial showed that mortality from prostate cancer was low, irrespective of treatment assignment. Prostate-cancer–specific survival was at least 98.8% in all groups, and there was no significant difference among the three randomized groups (P=0.48 by log-rank test). There was no evidence that between-group differences in prostate-cancer mortality varied according to age, PSA level, Gleason score, or clinical stage.

Morning Report Questions

Q: How do prostatectomy, radiotherapy, and active monitoring compare regarding disease progression and all-cause mortality in men with PSA-detected clinically localized disease?

A: In the trial by Hamdy et al., the incidence of disease progression was higher in the active-monitoring group than in the surgery and radiotherapy groups (112 men in the active-monitoring group, 46 in the surgery group, and 46 in the radiotherapy group; P<0.001 for the overall comparison). Deaths from any cause were evenly distributed across the treatment groups (P=0.87 by likelihood-ratio test), although the confidence intervals for the hazard ratios were wide and so did not provide strong evidence of equivalence across the groups.

Q: What are some of the limitations of the ProtecT trial?

A: There are several limitations of the ProtecT trial. First, the protocol was developed almost two decades ago; since then, treatments and diagnostic techniques for prostate cancer have evolved. The ProtecT trial did not use multiparametric magnetic resonance imaging to evaluate patients at diagnosis or during monitoring. Surgical techniques have changed with robot-assisted laparoscopic prostatectomy, and although all patients in the radiotherapy group received neoadjuvant androgen-deprivation therapy with three-dimensional conformal irradiation, new techniques such as intensity-modulated radiotherapy have been introduced, and brachytherapy was not included. Second, less than 1% of the participants enrolled in this trial were of African–Caribbean ancestry, but this percentage reflected the population in the recruiting centers who were in the trial age range.

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