Recurrence after Therapy for Oligometastatic Castration Sensitive PCa

[pjoshea13]

New study below [1].

"Metastasis directed therapy (MDT) is increasingly used in castration-sensitive oligometastatic prostate cancer (OPCa) because it prolongs progression free survival (PFS) and androgen deprivation free survival."

"Median follow up was 25.2 months and 50.4% of patients received concurrent androgen deprivation.

"Median time to PSA recurrence was 15.7 months,

"TTNI {time to next intervention} was 28.6 months,

"DMFS {distant metastasis free survival} was 19.1 months, and

"bPFS {biochemical progression free survival} was 16.1 months.

"Two-year OS {overall survival} of 96.8%."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/327...

Int J Radiat Oncol Biol Phys

. 2020 Aug 13;S0360-3016(20)34120-1. doi: 10.1016/j.ijrobp.2020.08.030. Online ahead of print.

Patterns of Recurrence and Modes of Progression Following Metastasis Directed Therapy in Oligometastatic Castration Sensitive Prostate Cancer

Matthew P Deek 1 , Kekoa Taparra 2 , Dyda Dao 2 , Luanna Chan 1 , Ryan Phillips 1 , Robert W Gao 2 , Eugene D Kwon 3 , Curtiland Deville 1 , Daniel Y Song 4 , Stephen Greco 1 , Michael A Carducci 5 , Mario Eisenberger 5 , Theodore L DeWeese 4 , Samuel Denmeade 6 , Kenneth Pienta 5 , Channing J Paller 6 , Emmanuel S Antonarakis 5 , Kenneth R Olivier 2 , Sean S Park 2 , Bradley J Stish 2 , Phuoc T Tran 7

Affiliations collapse

Affiliations

1 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine.

2 Department of Radiation Oncology, Mayo Clinic.

3 Department of Urology, Mayo Clinic.

4 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine.

5 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine.

6 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine.

7 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine. Electronic address: [e-mail].

PMID: 32798608 DOI: 10.1016/j.ijrobp.2020.08.030

Abstract

Purpose: Metastasis directed therapy (MDT) is increasingly used in castration-sensitive oligometastatic prostate cancer (OPCa) because it prolongs progression free survival (PFS) and androgen deprivation free survival. Here we describe patterns of recurrence and identify modes of progression following MDT using stereotactic ablative radiotherapy (SABR).

Methods and material: Two hundred and fifty-eight patients with castration-sensitive OPCa (≤ five lesions at staging) were retrospectively identified from a multi-institutional database. Descriptive patterns of recurrence and modes of progression were reported. Other outcomes including median time to PSA recurrence, time to next intervention (TTNI), distant metastasis free survival (DMFS), overall survival (OS) and biochemical PFS (bPFS) were reported. Survival analysis was performed using the Kaplan-Meier method and multivariable analysis (MVA) was performed.

Results: Median follow up was 25.2 months and 50.4% of patients received concurrent androgen deprivation. Median time to PSA recurrence was 15.7 months, TTNI was 28.6 months, DMFS was 19.1 months, and bPFS was 16.1 months. Two-year OS of 96.8%. On MVA factors associated with bPFS included age (HR 1.03, p = 0.04), N1 disease at diagnosis (HR 2.00, p = 0.02), M1 disease at diagnosis (HR 0.44, p = 0.01), initial PSA at diagnosis (HR 1.002, p = <0.001), use of ADT (HR 0.41, p<0.001), pre-SABR PSA (HR 1.02, p = 0.01), and use of enhanced imaging for staging (HR 2.81, p = 0.001).

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

[6357axbz]

Patrick, 50.4% of patients received concurrent androgen deprivation. Does that mean after MDT (radiation) they continued ADT, and the other half did not?

[jdm3 in reply to 6357axbz]

I was wondering the same thing. The use of ADT kind of muddles the results of SBRT. Hard to know which was the effective factor. Individually or combined. I had SBRT while on ADT so don't know if the SBRT alone would have been effective or vice-versa.

Johns Hopkins tried to recruit me for their whack-a-mole study using only SBRT for oligometatstatic PCa, but I followed the advice of my MO at Dana Farber and did the systemic ADT treatment along with the SBRT. They have results of the SBRT only cohort without ADT. That would be interesting to see.

[StayingOptimistic in reply to jdm3]

My RO at MSK told me” if we confirm that the lesion is PC, then we will do SBRT and a short course of ADT”. So it looks like this is what they do, combine both. I have not done anything about it yet.

[pjoshea13 in reply to 6357axbz]

That's how I read it.

The term "concurrent" follows "median follow up was 25.2 months" in the same sentence. Why would anyone treated for oligomets need ADT throughout the follow-up? That's long enough to develop CRPC, if indeed, there was residual cancer.

From the full text:

"Half of patients (50.4%) received concurrent ADT with radiation with median duration of 18.7 months".

Seems excessive?

"A very small percentage also received additional androgen receptor axis agents such as enzalutamide or abiraterone (1.6%) and one patient (0.4%) was also treated with concurrent docetaxel. Finally, 4.3% of patients received nelfinavir during SABR."

-Patrick

[6357axbz in reply to pjoshea13]

Where in this report does it differentiate the results of the 50.4% of patients receiving concurrent ADT and those who did not?

[pjoshea13 in reply to 6357axbz]

Table 3: Modes of progression

Control Oligo Poly

Total population

40.9% 36% 23.1%

No ADT

27.6% 44.8% 27.6%

Conventional imaging 46.1% 36.2% 17,7%

Enhanced imaging

36.3% 37.7% 26%

Columns: Long Term Control, Oligoprogressor, Polyprogressor

-Patrick

[pjoshea13 in reply to pjoshea13]

so much for my attempts to format in a readable way ... -P.

[6357axbz in reply to pjoshea13]

Ok I found the complete article elsewhere.

[6357axbz in reply to pjoshea13]

Thanks. I didn’t see any tables in the link you provided...

[MateoBeach]

Another study on SBRT for oligomets found about 2/3 of pts. Had recurrence at other sites within 2 years. Not great, but what about the rest? Did a significant minority have long term recurrence free? Unknown and this reporting of just the median or means ( middle of the bell curve) doesn’t provide info on the fat tail, if any. And mixing ADT with non ADT further muddies the waters.

I had SRT for two pelvic nodes on PSMA PET with no other sites presence so I was very hopeful. Did a short course of ADT during, then stopped it so to see if it worked. 10 months out it is still uncertain as PSA bouncing around at less than 0.20. But it can take a long time to reach a true nadir with such slow growing cells after the radiation insult. Waiting for the other shoe to drop.

[pjoshea13 in reply to MateoBeach]

It can be difficult to compare similar oligo studies. The definition of oligometastatic disease varies as does inclusion criteria & the actual cohort characteristics. Looking at the full text of the study I posted:

"Typically, men with five or less lesions seen on imaging were considered oligometastatic and appropriate for MDT. However, those with greater than five lesions were included in the analysis if all sites of disease were treated with definitive intent radiation."

"The median number of metastases initially treated was one". !!!

-Patrick