Wednesday, August 24, 2016

Probability of remaining recurrence-free after salvage radiation

In 2007, Stephenson et al. published a nomogram that predicted the probability of success of salvage radiation after post-prostatectomy biochemical failure. Biochemical failure was defined as a PSA≥0.2 ng/ml. Memorial Sloan Kettering Cancer Center has made the nomogram publicly available at this link. But that data was put together before ultrasensitive PSA tests became widely available, and before three randomized clinical trials demonstrated an advantage to adjuvant radiation over waiting. Several studies now suggest (see this link) that early salvage may provide the same benefit as adjuvant radiation therapy, but with less risk of overtreatment.

Tendulkar et al. have now updated the Stephenson nomogram.. The original nomogram was based on 1,540 patients treated between 1987 and 2005 at 17 tertiary care facilities. All patients had a confirmed PSA ≥0.2 ng/ml before SRT. Outcomes were based on 6-year progression-free probability after SRT. The updated nomogram is based on 2,460 patients treated between 1987 and 2013 at 10 academic medical centers. It included post-op ultrasensitive PSA test results for some (18 percent) of the patients, but only 18 patients were treated at a PSA≤0.05 ng/ml. The nomogram predicts 5- and 10-year probability of freedom from biochemical failure (PSA≥0.2 ng/ml) after SRT. The authors also constructed a nomogram that predicts 5- and 10-year probability of incidence of metastasis. Their model has a predictive accuracy of about 68 percent for freedom from biochemical failure, and 74 percent for incidence of metastasis.

Update (3/27/2018): Cleveland Clinic now has a more convenient online version of this nomogram on their website:
http://riskcalc.org/ProstateCancerAfterRadicalProstatectomyNew/

The tables below approximate the nomogram for predicting the 10-year probability of remaining free of biochemical failure after SRT treatment.


Risk Factor
Score (points)
Points
ADT
Yes: 0      No: 49

Gleason score
6: 0      7: 54        8: 70        9/10: 90

Extraprostatic Extension
No:0        Yes:22

Surgical Margins
Positive: 0         Negative: 27

Seminal Vesicle Invasion
No: 0      Yes: 24

Pre-RT PSA (ng/ml)
0.05: 2.5    0.1: 5   0.2:10    0.3: 15        0.5: 25     1.0: 50   1.5: 75

Radiation dose (Gy)
≥66 Gy: 0   <66 Gy: 17

Total points




Total points
Probability
100
70%
150
50%
195
30%
220
20%
245
10%
265
  5%

As an example, take the case of a man who, after his prostatectomy, had a Gleason score of 9 (=90 points), seminal vesicle invasion (=24 points), margins were negative (=27 points), PSA before SRT was 0.5 ng/ml (=25 points), and his radiation oncologist plans on treating him with a dose of 65 Gy (=17 points) without ADT(=49 points). His total score is 90+24+27+25+17+49= 232. This corresponds to about a 15% probability of success. The doctor and his patient probably would not consider this SRT treatment, given the risk of adverse side effects.

Now, let’s suppose the same man is treated earlier when his PSA is only 0.05 ng/ml (2.5 points) and his radiation oncologist proposes a dose of 70 Gy (=0 points) with ADT beginning two months before SRT (=0 points). His total score is 90+24+27+2.5+0+0= 143.5. This corresponds to about a 55% probability of success. This SRT treatment is a lot more tempting.


Because of database limitations, they could not incorporate PSA doubling time or increases in their model. They also could not include the duration of ADT use or more precise radiation dosage. With more data, a genomic classifier (Decipher®) also might improve the predictive accuracy of their model. Together with other factors like co-morbidities, risk of adverse effects and life expectancy, this nomogram should prove useful in helping the patient and doctor decide whether SRT is worthwhile.


Note: Thanks to Dr. Rahul Tendulkar for providing me with the full text of his original article.

7 comments:

  1. Interesting data. I arrived on this web site from another prostate cancer help site. When I put my data in, I was surprised that recurrence was such a high possibility. I am a 75 year old man who is 10 years past DaVinci Radical prostectatomy. What I have learned is that surgery is not the solution. Maybe urologist need to get out of the marketplace and let various forms of radiation do the job.

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    1. I'm sorry to hear that your PSA is rising, and the odds don't look as good as you'd like them to be. You are right that there are many options for the newly diagnosed patient, and the onus falls upon us to go seek out those alternatives.

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  2. I would think that positive margins would add points? Negative margins indicate that the cancer was more contained. Or do I have that backwards?

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    Replies
    1. Remember that this nomogram does NOT give the probability of a recurrence, it gives the probability that a recurrence can be cured. Think of it this way: with positive margins, you KNOW that the cancer is local, where it may potentially be cured by locally-directed salvage radiation; with negative margins, there is increased suspicion that the recurrence is distant, and therefore, not curable.

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  3. Thank you for the clarification. I am currently at this crossroad and will weigh this information carefully. I'm at a 214.5 with ADT and 165.5 without.

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    Replies
    1. You meant 214.5 without ADT (~22% chance of success) and 165.5 with ADT (~43% chance of success).

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  4. Yes!
    Lol, i'm having a dyslexic day!

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