ART NIH Predicting the Outcome of Salvage Radiation Therapy for Recurrent Prostate Cancer After Radical Prostatectomy

[RMontana]

Summary: Patients in this audience have had both radical prostatectomies (RP) and salvage radiation treatment (sRT) and want to know their chances of having recurrent prostate cancer. This study developed a predictive model called a nomogram that predicts the 6-year progression-free probability (PFP) after SRT for men with PSA recurrence after RP. The model used to predict the probability of disease progression after SRT is taken from a multi-institutional cohort of 1,603 patients. The resultant nomogram was internally validated and had a concordance index c of 0.69. c = 1 indicates perfect prediction accuracy and c = 0.5 is as good as a random predictor.

This study was concluded pre- PSMA Pet scan which would close the gap mentioned wherein sRT was provided to men with MET. Before any sRT is given today a PSMA Pet scan would be needed and should be SOC (standard of care) in order to determine if MET is present. In this case sRT is not an option. Should this study be replicated and patients failing the PSMA Pet are excluded, it would or should increase the c, or concordance index, appropriately.

For me, 9 months after the start of my ADT holiday, with a nadir of 0.001 ng/dL and 3 each uPSA (ultra low PSA) test results, my total now stands at 156. This means that I have a 57% chance of being PFP at 6 years post sRT...that would take me to 2026...time will tell. The 57% from the nomogram tracks other predictive models I have used, which range from a low of 50% upwards.

Details;

1. Median Time to MET - An estimated 25% of patients treated with radical prostatectomy (RP) for clinically localized prostate cancer will suffer recurrence of their disease. In the absence of salvage therapy (sRT), the median time from PSA recurrence to distant metastasis is 8 years.

2. Primary End Points – For this study they were;

a. disease progression after SRT, defined as a serum PSA value of 0.2 ng/mL or more above the postradiotherapy nadir followed by another higher value,

b. a continued rise in the serum PSA despite SRT,

c. initiation of systemic therapy after completion of SRT, or

d. clinical progression.

3. 6 Year Response from sRT - The 6-year response to SRT among patients treated at PSA levels of 0.50 ng/mL or less appears to be durable because only two progression events were observed after 6 years among 32 patients at risk at 6 years (error in Fig 1 which shows 11 at Risk for month 90; should be 30). 1,491 patients and their responses to sRT were available. For these;

a. a PSA nadir after radiotherapy of 0.10 ng/mL or less was achieved in 905 patients,

b. 726 patients did not receive ADT.

c. 600 patients received ADT.

4. Risk Subsequent PSA Progression - patients who experienced two or more PSA rises at levels of 0.2 ng/mL or higher or a single PSA level of 0.5 ng/mL or higher, are associated with a risk of subsequent PSA progression that is greater than 90%.

5. Efficacy of ADT Treatment - ADT administered before and/or during SRT was associated with improved PSA control in the study, although this may potentially be explained by the effects of prolonged ADT (up to 24 months in some patients) on masking PSA recurrence.

6. Use of Nomogram - The nomogram represents the best tool available (circa 2009; pre PSMA PET) to predict the outcome of SRT and is anticipated to be useful for medical decision making for patients with a rising PSA.

ncbi.nlm.nih.gov/pmc/articl...

[ElRanchoDePoisonIvy]

Some of these seem backwards. For example, negative surgical margins gets more points than positive. Or am I reading this wrong?

[RMontana in reply to ElRanchoDePoisonIvy]

Yes, that was my thought...after surgery I was told by my RO and my Surgeon that I was 'fortunate' to have positive margins AND BCR after surgery...counterintuitive! I believe the thinking was that its better to have a 'dirty' margin and fail than a clean one and not know where the cells are metastasizing; that was what I thought as well. Yes, its backwards in a way...but this is what they present.

I guess from their standpoint, if you had NEG margins after surgery AND had need for sRT as well, then this was a bad sign; the cells had escaped! The other killers for points are;

a. LN invasion

b. pre OP PSA, and

c. PSADT, doubling time, the real killer here...

PS, need to look for an update to this publication and a possible new version of the monogram, that incorporates PSMA PET...one thing that makes the c-index low at 0.67 out of 1.00 is that there are men back in the day who had MET but we lacked the scanning technology to prove this and locate the source of the PSA...this is now possible. So this nomogram would only improve in prognostic power including this new tech...let me know if you see anything along these lines...TNX

[ElRanchoDePoisonIvy in reply to RMontana]

Will do. It does seem bass ackwards for that parameter. The prostatectomy PSA seems odd too. Not sure why a higher PSA would yield fewer points.

[RMontana in reply to ElRanchoDePoisonIvy]

...again, this nomogram is to predict PFP (failure) for men who have had surgery and sRT...so, if you had need for both of these AND your PSA was low pre surgery, then the disease was not contained to the prostate and was metastatic from the get to...this is the thinking here...it seems backwards only because of where the nomogram is coming into use, after surgery and radiation, in hopes of predicting a 3d failure...TNX

[ElRanchoDePoisonIvy]

Ah. I see.