Quest — Winter 2016
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The ProtecT Trial: Comparing Surgery, Radiation And Surveillance For Localized Prostate Cancer At 10 Years Follow-Up

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.

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.

The ProtecT trial was designed to improve clinical outcomes in men with PSA-detected clinically localized prostate cancer. In the study, 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 (545, 553, and 545 men respectively). 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 low (1%) across all treatment groups. This was even 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. Thirty-three men in the active monitoring group developed metastatic disease, compared to 13 men in the surgery group and 16 men in the radiation group. In the active monitoring group, 112 men had disease progression, compared to 46 men each in the surgery and radiation therapy 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.

Primary treatment failure

At the end of the reported follow-up, 85% of the men in the radiation therapy or surgery groups had received a “radical intervention,” defined as radical prostatectomy, radiation therapy, or high-intensity focused ultrasound therapy.

Of the 391 men who had a prostatectomy, 18 had primary treatment failure. Half had a PSA level of 0.2 ng/ml or higher after surgery and received salvage radiation and longterm ADT. The others received adjuvant radiation within a year after surgery due to tumor spread outside the prostate or positive surgical margins.

Of the 405 men who started radiation therapy within 9 months of being assigned to the treatment group, 14% had an increase in PSA levels of 2 ng/ml or more above the lowest value after starting treatment. Three of these men had a salvage prostatectomy, 14 had long-term ADT, and 1 had high-intensity focused ultrasound therapy.

AS failure rates

The purpose of active monitoring was to minimize the risk of over-treatment by avoiding immediate intervention, and to regularly monitor disease progression and treat if necessary.

More than half the 545 men (54%) assigned to active monitoring ended up having a radical intervention: 49% had surgery, 33% had radiation therapy, 22% had brachy therapy, 9% had radiation to areas other than the prostate gland, and 1% had 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.

The URF appreciates your support. Our mission is to advance research and education for the prevention, detection, treatment and cure of prostate cancer.

ADT Type, Duration and the Risk of Diabetes

Arecent study investigated the association between the types and duration of androgen deprivation therapy (ADT, or hormone therapy) and the risk of type 2 diabetes. Researchers used data from the Prostate Cancer database Sweden and compared diabetes risk in 34,031 men with prostate cancer on various types of ADT: anti-androgens (9,143 men), surgical removal of the testicles (3,014 men), or gonadotropin-releasing hormone agonists (21,874 men).

When compared to men without prostate cancer, men on gonadotropin-releasing hormone agonists and the surgical testicle removal group had an increased risk of type 2 diabetes during the first 3 years of ADT. The risk decreased thereafter. There was no increased risk seen in men on antiandrogens. The authors concluded that men on ADT, even for a limited period of time such as with radiation therapy, had an increased risk of type 2 diabetes.