5-ARI delays prostate cancer progression in men with low-risk disease – ModernMedicine

The 5-alpha-reductase inhibitor dutasteride Avodart appears to delay disease progression and the initiation of active treatment in men with low-risk, localized prostate cancer, results of a 3-year international clinical trial indicate.Treatment with dutasteride also reduces cancer-related anxiety, study authors found.”The results prove that using active surveillance plus dutasteride is a viable, safe, and effective treatment option for men who often undergo aggressive local treatment despite low risk of dying from the disease,” said first author Neil Fleshner, MD, of the University of Toronto’s Princess Margaret Hospital.

via 5-ARI delays prostate cancer progression in men with low-risk disease – – ModernMedicine.

This is the first study I’ve seen that shows that 5-alpha-reductase inhibitors may help slow the progression of prostate cancer.  These medicines are tolerated well by most patients and treatment with avodart can be considered.

Determinants of Long-Term Retention of Prostate Cancer Patients in Active Surveillance Management Programs

From Urotoday and the AUA

Of the 2134 PCa cases, 169 (7.9%) had AS as their initial management. Of the 169 AS cases, 89 (53%) remained untreated throughout follow-up (mean 7.1 years) and the remaining 47% received treatment an average of 3.1 years post-diagnosis. Significant predictors of eventual active treatment in multivariate models included younger age at diagnosis (60-69 vs. 70+ years), higher Gleason score (>6 vs. <6), and higher prostate cancer aggressiveness/risk. The researchers observed similar rates for development of clinical metastases and PCa death in both AS and immediate treatment groups, respectively (metastases: N=8 and N=92, 6.5 vs. 6.7 events per 1,000 person-years, p=1.0; PCa death: N=4 and N=51, 2.4 vs. 2.7 deaths per 1,000 person-yrs, p=1.0).

This one study shows that men that did active surveillance, needed therapy about half of the time. The results seemed similar for both groups. My main concern is that we do not know the cancer characteristics of the patients. It is possible that the active surveillance patients had less cancer than the treated patients and should have done better.
I also think that waiting 3 years to treat someone may later the treatment approach and possibly lead to more side effects after therapy.

Active Surveillance for Prostate Cancer Patients

From Medscape

May 12, 2008 — The urine test for the PCA3 gene, already marketed for use in diagnosing prostate cancer, could also be useful in prognostication. It might have clinical application in selecting men with low-grade and low-volume tumors who would be suitable candidates for active surveillance, say researchers writing in the May issue of the Journal of Urology.
The PCA3 urine test, marketed in Europe by Gen-Probe, has been shown in previous studies to be more accurate in diagnosing early prostate cancer than serum levels of prostate-specific antigen (PSA).

I usually use the PCA 3 test for men who have had a negative biopsy and we are considering performing a second one. I usualy use it for men with high grade PIN after one biopsy. If the PCA 3 is positive, I usually perform a second biopsy. I have not looked at my data to see if the above correlation exists, but that would be interesting.
I also am not sure if you can use PCA 3 tests that are taken a few months apart to mean anything. For example, would a rise in PCA 3 be expected if a man develops cancer or the cancer is growing?

Cryosurgery better than watchful waiting for elderly?

Straightfromthedoc: JAMA Study Confirms Prostate Cancer Treatment is Preferable over “Watchful Waiting”
According to Endocare President, Chairman and CEO Craig T. Davenport:
“This study offers further scientific evidence that ‘watchful waiting’ may not be the best option for many patients, particularly when there are effective, minimally invasive treatments like cryoablation available. Based on the results of the study, ‘watchful waiting’ patients should consider some kind of treatment.
We believe cryoablation is an excellent option for many patients given its proven, long-term cancer control rate, low morbidity, and typically fast recovery time. Additionally, we believe cryoablation is a particularly good option for ‘watchful waiting’ patients who are not able to tolerate surgery or radiation, or for men with very small amounts of cancer in their prostate.”
Straight from the doc reported on a press release from endocare, a company that is a leader in cryosurgery.
I am a supporter of cryosurgery and discuss it as an option for all prostate cancer patients, but I thought that some of the conclusions were not supported by the paper.
The JAMA article that I have previously discussed only looked at surgery and radiation, bot cryosurgery. The press release did not state this.
Elderly men with very small tumors are candidates for watchful waiting and cryosurgery is not without side effects.

Survival advantage with surgery for elderly patients with prostate cancer?

JAMA — Survival Associated With Treatment vs Observation of Localized Prostate Cancer in Elderly Men, December 13, 2006, Wong et al. 296 (22): 2683

Conclusions
This study suggests a survival advantage is associated with active
treatment for low- and intermediate-risk prostate cancer in elderly men
aged 65 to 80 years. Because observational data cannot completely adjust
for potential selection bias and confounding, these results must be
validated in randomized controlled trials of alternative management
strategies in elderly men with localized prostate cancer.

An important paper was recently published in JAMA that concluded that men between 65 and 80 may do better with surgery or radiation than with watchful waiting.
The authors did a good job with this observational study. They looked at all men with prostate cancer and compared those who had treatment with radiation or surgery and compared them to men who did not receive therapy for at least 6 months after diagnosis.
They found that there was a 30% lower mortality in the men that had therapy. The authors made an effort to compare the men with regard to other medical conditions and pointed out that without a randomized trial, there may be a selection bias since most urologists counsel men with good 10 year life expectancies to undergo therapy and men with poor life expectancies to have watchful waiting.
This is one study that I can use to help guide patients, but not an absolute decision maker in my opinion.
I reviewed my patients to see how many men I did robotic prostatectomies on. Over my first 200 robotic prostatectomies I operated on 19 men that were 70 or older:
5 were 70
11 were 71-74
1 was 76,78, and 80
I typically counsel them based on their health, the aggressiveness of their cancer and tell these men they will likely be equally cured with surgery or radiation.
12 of the 19 went home in 1 day, 6 in 2 days, and 1 in 3 days. The only medical problem I had was one patient who was re-hospitalized with a pulmonary embolus (blood clot in lung) a few days after going home and did well on blood thinners.
I do feel that these men often have significant BPH symptoms that is greatly helped by surgery. They do seem to have more incontinence in the short run, but they have done well. 9 of the prostates were big (larger than 50 grams), 5 were very big (greater than 75 gms), and 1 was huge (123 grams).
As for continence, 8 of the 15 that I have data on had 1 pad or less incontinence at 1 month, and 8 of 11 had 1 pad or less incontinence at 3 months, and 7 of 7 were in 1 pad or less at 6 months.

Watchful waiting vs. definitive therapy

UroToday – What is the Best Approach for Screen-Detected Low Volume Cancers?
What is the Best Approach for Screen-Detected Low Volume Cancers?
BETHESDA, MD (SUO 7th Annual Meeting – December 1-2, 2006:NIH) – In a session moderated by Dr. Eric Klein, Cleveland Clinic, Dr. Laurence Klotz, University of Toronto presented the “The Case for Observation”.
My patients know where I stand on this. I am certainly on the side of Drs. Blute (Mayo Clinic) and Montie (University of Michigan) favoring radical prostatectomy.

Watchful waiting for prostate cancer

UroToday – European Urology – Watching the Face of Janus- Active Surveillance as a Strategy to Reduce Overtreatment for Localised Prostate Cancer
A good abstract by Swedish urologists that addresses many of the issues for watchful waiting.
It points out that the best candidates have a small amount of gleason 6 cancer. Most men did well for several years with this option.
These people should have repeat biopsies at intervals and may have a negative psychological impact from choosing this therapy.
I always discuss watchful waiting as a possible therapy with newly diagnosed cancer.

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