The ProtecT Study

I'm just trying to make sense of the new ProtecT paper from the UK [1]. The NY Times made it a front page story this morning. [2]

"Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545)." [1]

Seems odd that almost 62% of the 2,664 men were OK with the idea of a computer allocation to one of the three arms.

"... about three quarters had a Gleason score of 6; the rest had higher Gleason scores." [2]

So, two-thirds of the three-quarters who were GS=6 received treatment.

Put another way, one-half of the men received treatment, in spite of being GS=6.

& one-twelfth of the men were assigned to active monitoring in spite of GS=7-10.

Three-quarters of each treatment arm were GS=6, & this can only serve to make the statistics look way better than they actually are.

One-quarter of the men in the active monitoring arm were GS=7-10, & this would make the active monitoring statistics took worse.

"Metastases developed in more men in the active-monitoring group (33 men ...) than in the surgery group (13 men ...) or the radiotherapy group (16 men ...)"

"Higher rates of disease progression were seen in the active-monitoring group (112 men ...) than in the surgery group (46 men ...) or the radiotherapy group (46 men ...)"

So what's the message? That one should weigh the morbidity of treatment against double the risk of metastases?

It would be more useful to newly diagnosed men, to have these statistics reported by Gleason score.

...

"Of the 17 total prostate cancer–specific deaths, some were in men with low-risk disease, and that is troublesome, Dr Hamdy noted. "We cannot describe lethal disease well at diagnosis. We need new markers to tell us that," he said." [3]

By "low-risk", he presumably meant GS=6. Well, more than 25% of GS=6 men in active monitoring will progress. Active monitoring shouldn't mean waiting for mets to appear - which is what seems to have happened for 33 men. The 4-K test or something similar should have been part of the monitoring.

"An important aspect of this study design is outdated, said Stacy Loeb, MD, a urologist at New York University's Langone Medical Center, who was not involved with the study.

"Overall, the protocol of active monitoring used in ProtecT is different from that used in contemporary active surveillance programs," she said.

"In the ProtecT study, prostate biopsies were not part of regular scheduled monitoring but could be used as part of the clinical assessment of disease progression, she said.

"Dr Loeb pointed out that this differs from modern active surveillance programs, which include serial PSA testing and digital rectal examination, as well as serial prostate biopsies to check for increases in the grade or volume of the cancer.

"She also noted that in the Johns Hopkins active surveillance program, patients with very-low-risk and low-risk prostate cancer are monitored with PSA testing and prostate exams every 6 months, as well as yearly prostate biopsies.

"Dr Loeb pointed out that since the inception of this program in 1995, approximately 1300 patients have been enrolled and only 2 have died of prostate cancer. The 15-year prostate cancer–specific survival rate was 99.9% and metastasis-free survival rate was 99.4%.

""This suggests a very low risk of developing incurable disease for low-risk patients who are monitored closely," she said. "

"Dr Loeb also pointed out that other tests, such as biomarkers and MRI, are being integrated into active surveillance, which were not available when ProtecT started."

...

Another ProtecT paper has just appeared [4]: "Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer."

"In terms of sexual function, 67% of the study population reported erections firm enough for intercourse, but at 6 months, this fell to 52% of the monitoring group, 22% of the radiotherapy group, and 12% of the prostatectomy group." [3]

"Radiation therapy had the most negative effect on bowel function at 6 months compared with the other two groups, and some bowel symptoms developed over time." [3]

""After 6 years, about 1 out of 5 men still needed to use pads for urinary incontinence," Dr Donovan said about the surgery group. "Some men recover, but some have longer and more lasting effects," she added. At 6 years, this 17% compared unfavorably with the 8% of the active monitoring group who needed pads and 4% of the radiation therapy group." [3]

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/276...

[2] nytimes.com/2016/09/15/heal...

[3] medscape.com/viewarticle/86...

[4] ncbi.nlm.nih.gov/pubmed/276...

9 Replies

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  • Good review of this study

  • Last night, I attended an UsTOO support group meeting in NYC and the guest speaker was Dr. Michael Morris of MSKCC. He had a few comments about this study and this was the most memorable and important: "If the message of this study is received as saying that high risk patients do just as well on active monitoring as they with treatment, then this is the wrong message."

    Yes, this is obvious to most of us, but it is pathetic that the NY Times' summary of the NEJM study might very well be interpreted in this way. Because of the way the study was conducted, I believe it is not helpful, especially for anyone with high risk disease.

  • Here is how TheHuffingtonPost.com reported it:

    Headline:

    "Treating Prostate Cancer Is Often No Better Than Doing Nothing"

    "Indeed, no matter what approach the men were randomized to, they weren’t likely to die of either the cancer itself, cancer treatment or other causes after ten years."

    [1] huffingtonpost.com/entry/th...

    I suppose the The U.S. Preventive Services Task Force (USPSTF) would approve.

    -Patrick

  • Have you ever reviewed the make up of the U.S. preventative Services Taslforce? Notice how many career prostate cancer pros on the task force? Urologists, Radiation Oncologist, or Medical Oncologists?

    Gourd Dancer

  • It was the first thing I did.

    ~50% female

    -2 pediatricians

    -academics & administrators

    etc, but I have never posted the list before.

    Currently:

    Kirsten Bibbins-Domingo, Ph.D., M.D., M.A.S. is the Lee Goldman, MD, endowed chair in medicine and professor of medicine and of epidemiology and biostatistics at the University of California, San Francisco (UCSF). She is a general internist

    Susan J. Curry, Ph.D., is dean of the University of Iowa College of Public Health, where she also serves as a distinguished professor of health management and policy. Her work focuses on health policy

    David C. Grossman, M.D., M.P.H., is senior investigator at the Group Health Research Institute and medical director for population health strategy and a practicing pediatrician at Group Health in Seattle, WA.

    Karina W. Davidson, Ph.D., M.A.Sc., is a professor in the Departments of Medicine, Cardiology, and Psychiatry and the director of the Center for Behavioral Cardiovascular Health at Columbia University Medical Center. She is also a psychologist in the Department of Psychiatry at New York Presbyterian Hospital/Columbia University Medical Center.

    John W. Epling, Jr., M.D., M.S.Ed., is the professor and chair of family medicine at the State University of New York (SUNY) Upstate Medical University. Dr. Epling is also a professor in the Department of Public Health and Preventive Medicine. Dr. Epling serves as medical director for the Central New York Region Office of the New York State Area Health Education Center System.

    Francisco A.R. García, M.D., M.P.H., is the director and chief medical officer of the Pima County Department of Health in Tucson, AZ. Dr. García's research and clinical expertise is in the area of premalignant cervical disease and human papillomavirus infection affecting the female lower genital tract, as well as in the evaluation of new technologies and therapeutics for cervical cancer precursors.

    Alex R. Kemper, M.D., M.P.H., M.S., is a board-certified pediatrician and professor of pediatrics at Duke University Medical School.

    Alex H. Krist, M.D., M.P.H., is an associate professor of family medicine and population health at Virginia Commonwealth University

    Ann E. Kurth, Ph.D., C.N.M., M.S.N., M.P.H., is dean of the Yale School of Nursing

    C. Seth Landefeld, M.D., is the chairman of the department of medicine and the Spencer chair in medical science leadership at the University of Alabama at Birmingham (UAB) School of Medicine. Dr. Landefeld also serves on the board of directors of both the UAB Health System and the University of Alabama Health Services Foundation. Previously, Dr. Landefeld served as a professor of medicine and of epidemiology and biostatistics at the University of California, San Francisco (UCSF). While at UCSF, Dr. Landefeld made significant contributions to the School of Medicine’s geriatrics program

    Carol M. Mangione, M.D., M.S.P.H., is the Barbara A. Levey, MD, and Gerald S. Levey, MD, endowed chair in medicine at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) and professor of public health at the UCLA Fielding School of Public Health.

    William R. Phillips, M.D., M.P.H., is the Theodore J. Phillips endowed professor in family medicine in the School of Medicine and clinical professor of health services and epidemiology in the School of Public Health at the University of Washington, Seattle.

    Maureen G. Phipps, M.D., M.P.H., is the department chair and Chace-Joukowsky professor of obstetrics and gynecology and assistant dean for teaching and research on women's health at the Warren Alpert Medical School of Brown University.

    Michael P. Pignone, M.D., M.P.H., is a professor of medicine and inaugural chair of the Department of Internal Medicine at the Dell Medical School at The University of Texas at Austin. Dr. Pignone is an experienced author, researcher, and lecturer.

  • i think it would behove an individual, when first diagnosed, to slow down, do some investigation into the various options and their side effects, before making a decision on which way to go.the law of requisite variety indicates the more options you avail yourself, the more likely you will choose the one most appropriate

  • Too many guys go along with anything the guy in the white jacket says.

  • The study seems to have been misguided. Watchful waiting is to avoid needless intervention, where disease progressing can still be handled with curative intent.

    The measure of the failure of watchful waiting is the loss of curative intent, according to the current standards of the field. This means certainly bone mets, and probably lymph node mets, and I would say also certainly detection of circulating tumor cells or prostate cells that have undergone mesenchymal transition.

  • And as was said, that study should have been reported by Gleason score at randomization.