The Protect Trial:

Comparing Surgery, Radiation and Surveillance for Localized Prostate Cancer at 10 Years Follow-Up

Categories: Winter 2016
The latest results from the ProtecT trial, a large UK-based randomized study, compared radical prostatectomy, external beam radiation therapy, and active monitoring for patients who had PSA testing and were diagnosed with localized prostate cancer. The study focused on the rates of men who died from prostate cancer, developed metastatic prostate cancer or had disease progression in each type of treatment.
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Long-term trials can provide a distinct perspective on critical issues in clinical care. © Dan Oldfield

Since the advent of PSA testing, there has been a dramatic increase in the diagnosis and treatment of prostate cancer. However, PSA testing remains controversial due to concerns about overtreating tumors that would never cause harm and side effects of treatment, such as urinary or sexual dysfunction.

In the ProtecT trial, a total of 82,429 men ages 50 to 69 years received a PSA test from 1999 to 2009. Of the 2,664 men diagnosed with prostate cancer, 62% (1,643 men) agreed to be randomized into groups for either active monitoring, surgery, or radiation therapy. The median age was 62 years, and the median PSA level was 4.6 ng/ml.

Study results

At a median of 10 years follow-up, prostate-cancer-specific death was lower than the researchers had expected. Only 17 men died from prostate cancer, 8 in the active monitoring group, 5 in the surgery group, and 4 in the radiation therapy group. All-cause mortality was also low at approximately 10%.

However, rates of disease progression and metastatic disease were significantly higher in the active monitoring group than in the surgery or radiation groups. Metastatic disease was defined as bony, soft tissue, or lymph-node metastases on imaging or PSA levels above 100 ng/ml. Patients were considered to have disease progression if they had evidence of metastases, diagnoses of clinical stage T3 or T4 disease, long-term androgen- deprivation therapy (ADT, or hormone therapy), ureteric obstruction, rectal fistula, or the need for a urinary catheter due to local tumor growth.

Dr. Catalona’s Opinion

In patients with early prostate cancer diagnosed because of a screening program, 15- to 20- year follow-up is needed to evaluate the effectiveness of active surveillance versus immediate treatment with surgery or radiation therapy. In the ProtecT trial, it is already clear by 10 years that cancer progression is more common in men managed with active surveillance. It is highly likely that this difference ultimately will translate into a cancer- specific survival advantage for early treatment of patients who have some aggressive tumor features.

Primary treatment failure

More than half the 545 men (54%) assigned to active monitoring ended up having a radical intervention. “Radical intervention” was defined as radical prostatectomy, radiation therapy, or high- intensity focused ultrasound therapy.

This rate of failure illuminates the need for better clinical tools to identify the patients who are best suited for active surveillance (AS). This is a focus of Dr. Catalona’s SPORE research project, Impact of germline genetic variants on active surveillance for prostate cancer. This project seeks to identify genetic variants that indicate a patient is more likely to “fail” AS, and thus should be monitored more closely. See page 5 for information on getting involved in the study.

Looking ahead

The study authors estimated that based on their results, treating 27 men with prostatectomy rather than active monitoring would avoid 1 patient having metastatic disease, and treating 33 men with radiation therapy rather than active monitoring would avoid 1 patient having metastatic disease.

The results show the effectiveness of immediate treatment over active monitoring, but they have not yet translated into significant differences in mortality rates. Longer follow-up is needed.

N Engl J Med. 2016 Oct 13;375(15):1415-1424. Epub 2016 Sep 14.

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