So one of the more important papers that will be presented at the ASCO meeting in Chicago today will give us the 10-year results of the Canadian PCS IV trial.
This trial was designed to give us an answer to the question of how long a man with high-risk localized prostate cancer needs to be on androgen deprivation therapy (ADT) along with prostate-specific and pelvic radiation therapy. The historic standard time has been 3 years, but there have long been data suggesting that 18 months might be sufficient, even for men with high-risk disease. We have already known for a while that even shorter periods of ADT were appropriate for men with less aggressive forms of localized prostate cancer.
Now for clarification, we are referring here to men with high-risk prostate cancer but no sign of regional metastasis. So these are men with have any one of the following:
- A clinical stage of T3 or T4
- A Gleason score of 8 to 10
- A PSA level of > 20 ng/ml
but also …
- No sign of metastasis to the lymph nodes (i.e., they must have N0 disease).
In the paper to be presented today, Nabid et al. (abstract no. 5008) will report data showing the following:
- They randomized 630 men with high-risk prostate cancer to prostate-specific and pelvic radiation with along with either
- 36 months of ADT (in Arm 1; n = 310) or
- 18 months of ADT (in Arm 2; n = 320)
- The median follow-up was 9.4 years.
- At the time of median follow-up
- 147 men had died in Arm 1.
- 143 men had died in Arm 2.
- The 10-year overall survival rate was
- 62.4 percent for Arm 1
- 62.0 percent for Arm 2
- which was not statistically significant (p = 0.8412; hazard ratio [HR] = 1.024)
- Quality of life analysis showed a statistically significant benefit for men in Arm 2 compared to men in Arm 1.
The authors conclude that, for men with high-risk prostate cancer:
ADT combined with [radiation therapy] can be safely reduced from 36 to 18 months without compromising outcomes or [quality of life]. 18 months of ADT represents a new standard of care in [high-risk prostate cancer].
This is clearly a “big deal” in the treatment of high-risk localized prostate cancer, because it will not only lower the time than men have to be on ADT; it will also lower their risk for the long-term side effects of extended time on ADT.
The “New” Prostate Cancer InfoLink hopes that the results of this trial (which confirm earlier results from similar trials) will be rapidly adopted across the entire prostate cancer treatment community and built into all of the relevant treatment guidelines as quickly as possible.
We should be clear, however, that for men with node-positive (N1) prostate cancer who are treated with a combination of radiation therapy + ADT, the recommended time on therapy is still 3 years.
Filed under: Diagnosis, Living with Prostate Cancer, Management, Risk, Treatment | Tagged: "high risk", ADT, localized, radiation |
THE "NEW" PROSTATE CANCER INFOLINK 
You covered this in 2013 when it was presented at the GU Cancer Symposium. There was shorter median follow-up, but the 10-year results were almost exactly the same (see this link). In the recent AUA guidelines, they mentioned this study in passing, but cast some doubt on it because it has not yet appeared in a peer-reviewed publication. Because of that, they left their recommendation at 2-3 years. Although I would very much like to agree that 18 months is enough, I wonder why it has not been published in all this time. Certainly, it is important enough.
Sitemaster,
Could you please answer a few questions I have about the study. Is it correct that after the initial treatment with either 18 months or 36 months of ADT, none of the men had any further treatment and the prostate cancer just ran its course? If the men did have further treatment, wouldn’t the results of the trial be affected by such treatment? Why was OS used as an endpoint, and not prostate cancer-specific survival? Finally, is it correct that NO status was determined by a conventional CT scan, which means there were men in the NO category who actually had N1 disease and it may have been detected by one of the newer scans (e.g., [11C]choline scan), which further confounds the results for clinical application today?
Thank you.
Richard
Allen:
They may just have been waiting for the 10-year data. What do I know?
Dear Richard:
I am quite sure that any patient in this trial who had progressive disease after RT + ADT would have gone on to have further therapy. That would have been the case regardless of which arm of the trial they were in, so it would not have been likely to affect the results at all.
Overall survival is always the ultimate endpoint in trials like this. Prostate cancer-specific survival is much less relevant because just being on ADT can lead to serious cardiovascular consequences — up to and including death.
I would assume that (almost certainly) all the men in this trial would have had bone scans and CT scans prior to initiation of treatment, and that at that time (10+ years ago) there were no other available imaging tests by which to determine the presence of visceral metastasis. This is the nature of clinical trials — especially when they take a long time to conduct. However, once again, I don’t see why this would affect the results of the trial significantly because it would have been equally true in both arms of the trial.
The vast majority of men today still only get CT scans for risk of visceral metastases. The other forms of scan simply aren’t available to most patients as yet — for financial, geographical, and other reasons.
Prostate cancer specific survival was a secondary endpoint (for the reasons the Sitemaster explained). The Sitemaster previously reported on their 2013 presentation.
The 10-year prostate cancer-specific survival rates were:
• 87.2 percent for men in Arm 1
• 87.2 percent for men in Arm 2
So no difference in that either.
How is overall survival calculated? The results indicate how many men in each arm had died. And those stats result in OS of a little more than 50% in each arm.
Bob:
Average (median) overall survival is computed in terms of both the number of men surviving and also, importantly, how long they survived for while on therapy. Thus (just as a very simple example) … if the 50% of men who died in one arm of the trial all did so within 6 months and in the other arm of the trial the 50% of men who died all did so after 3 years, the two different groups of patients would have very different median overall survival times. These differences are normally best shown on what are known as Kaplan-Meier plots.
Here’s a link to a relatively simple article that discusses all this … but it does require a little patience to understand some of this.
Sitemaster:
Thanks for the explanation. Not being a statistician my take away is to fight this disease as aggressively as possible and let the chips fall where they may.
Is it possible to be classified T4 without exhibiting regional or distant metastasis of any type? If so, what does T4 imply in this context?
Rick:
Yes. T4 disease is defined by tumor that shows no evidence of N+ or M+ disease and in which tumor is still localized to the pelvic region, but has definitely escaped from the prostate and seminal vesicles. Tumor is normally either fixed to or invades surrounding areas, such as the bladder neck, the external sphincter, the rectum, the levator muscles, and/or the pelvic wall.
However, … This use of the T4 definition is rare today because in many T4 patients we can now do scans that weren’t available just a couple of years ago, and so T4 disease might no longer be the appropriate stage because we can now see micrometastasis that could be seen before.