Latest study on Active Surveillance and Prostate Cancer

This is the latest  study published on the New England Journal of Medicine on Active Surveillance (AS) for men with prostate cancer. If you have been recently diagnosed and have not been treated for prostate cancer, ask your doctor if you are a candidate for AS. It is a good idea to get at least 3 other physician opinions to make sure.

Details of the study:

 

• Randomized trial comparing radical prostatectomy with observation in 731 men who had received a diagnosis of clinically localized prostate cancer

• Average age was 67 years.

• Nearly one-third were African-American.

• Approximately 85% reported they were fully active.

• The average prostate specific antigen (PSA) was 7.8 ng/mL

• Approximately 43% had low risk, 36% had medium risk and 20% had high-risk prostate cancer.

• By the end of the study, 354 men (48.4%) had died

• Among men in the radical-prostatectomy group, 171 (47.0%) died, as compared with 183 (49.9%) in the observation group (not much of a difference)

• Average survival was 13.0 years in the radical-prostatectomy group and 12.4 years in the observation group. (not much of a difference).

• At 12 years, 40.9% of men assigned to radical prostatectomy and 43.9% of those assigned to observation had died.

• Death attributed to prostate cancer or treatment of prostate cancer occurred in 52 men total (7.1%)

• Two thirds of the deaths due to prostate cancer (34 of 52 deaths, accounting for 4.7% of all patients) were considered to be definitely due to prostate cancer or treatment or prostate cancer.

• Prostate-cancer mortality was identical in the observation and radical-prostatectomy groups at 4 years.

• As compared with observation, surgery did NOT reduce all-cause mortality among men with a PSA value of 10 ng per milliliter or less

• Prostate-cancer mortality was lower in the radical-prostatectomy group than in the observation group among men with a PSA value of more than 10 ng per milliliter (5.6% vs. 12.8%, P=0.02) and among men with high-risk prostate cancer ( By the way, a P-value of 0.02 is statistically significant but you would think it would be more so in with high risk disease).

• Prostate-cancer mortality was NOT significantly lower in the radical-prostatectomy group among men with a PSA level of 10 ng per milliliter or less (P=0.82) or among those with low-risk tumors (P=0.54) or intermediate-risk tumors (P=0.12)

• intermediate-risk tumors (determined by a PSA value of 10.1 to 20.0 ng per milliliter, a score of 7 on the Gleason scale, or a stage T2b tumor),
• Perioperative complications during the first 30 days after surgery occurred in 21.4% of men in the radical-prostatectomy group who underwent radical prostatectomy and included one death. The most common complication was wound infection, in 4.3% of the men

• Complications occurring in more than 2% of the men included urinary tract infection, surgical repair, bleeding requiring transfusion, and urinary catheterization more than 30 days after surgery.

• At 2 years, patient-reported urinary incontinence and erectile dysfunction, but not bowel dysfunction, were significantly more common among men who were randomly assigned to radical prostatectomy than among those randomly assigned to observation

• Among men with clinically localized prostate cancer that had been diagnosed after PSA testing came into practice, our study showed that radical prostatectomy did not reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up.

• Only 10% of patients were younger than 60 years of age. Longer follow-up may be important for the minority of men with prostate cancer who were younger than 60 years of age.

• Conclusion: Among men with localized prostate cancer detected the early, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up (Wilt et al. 2012).

 

My take on this

Active Surveillance (AS) is clearly a viable option for men with low-grade prostate cancer.  About 65% of men diagnosed with prostate cancer have low-grade disease defined by the D’Amico classification but roughly 90% get treated with either surgery or radiation (Cooperberg et al. 2010).  The D’Amico low-risk definition of prostate cancer is a Gleason score 6,  PSA 10 ng/ml or less,  Stage T1.

Focal therapy where the prostate stays in tact but only tumors are destroyed lies in between AS and aggressive treatment but these treatments have not been studied long-term and / or are not FDA approved in the United States. The most popular focal therapies include, High Intensive Focal Ultrasound (HIFU), photodynamic therapy and most recently, Laser ablation therapy. HIFU is approved as a treatment option in virtually every other country except the United States.

Also, it is important to note that since 2002 when the term “ Active Surveillance” related to prostate cancer became official, the term “ Watchful Waiting” declined in its use. Watchful Waiting(WW) is the process of “watching and waiting” for cancer to get worse before palliative treatment. AS involves close monitoring of patients with the intention to cure if there are any sign of prostate cancer progression.

Also, it is difficult for physician’s to pin down with accuracy the disease progression of any patient using biopsy, PSA and nomograms. So there’s always the possibility of determining someone is a good candidate for AS when they are not. However, here is another reason why AS is superior to WW – if AS is not appropriate for the right patient, that would be known relatively early with stringent observation by a qualified physician.

This is not the first study indicating AS is favorable to the right patient population. One report showed that out of 453 patients on AS followed up for 8 years only five died of prostate cancer. There was a much higher rate of mortality from caused unrelated to prostate cancer(Krakowsky et al. 2010).

Lastly, I vehemently promote an active lifestyle that creates a more hostile physiological environment to cancer cells. One randomized study indicates that an intensive lifestyle change, similar to the CaPLESS program (Plant-based, Mediterranean diet, Exercise and Smart Supplementation – more on this to follow – stay tuned), can slow the progression of prostate cancer in men on AS after two year follow-up (Frattaroli et al. 2008).

 

Reference:

Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, Gingrich JR, Wei JT, Gilhooly P, Grob BM, Nsouli I, Iyer P, Cartagena R, Snider G, Roehrborn C, Sharifi R, Blank W, Pandya P, Andriole GL, Culkin D, Wheeler T; Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012 Jul 19;367(3):203-13.

Cooperberg MR, Broering JM, Carroll PR. Time trends and local variation in primary treatment of localized prostate cancer. J Clin Oncol 2010;28:1117-1123

Krakowsky, Y., Loblaw, A. & Klotz, L. Prostate cancer death of men treated with initial active surveillance: clinical and biochemical characteristics. J. Urol. 184, 131–135 (2010).

Frattaroli J, Weidner G, Dnistrian AM, Kemp C, Daubenmier JJ, Marlin RO, Crutchfield L, Yglecias L, Carroll PR, Ornish D.Clinical events in prostate cancer lifestyle trial: results from two years of follow-up. Urology. 2008 Dec;72(6):1319-23.