Local therapy in patients with newly diagnosed oligometastatic prostate cancer

[pjoshea13]

New meta-analysis below.

My radical prostatectomy of 12 years ago would not have occurred if there were metastases. Nowadays, there seems to be an increasing view that debulking has benefit.

"Seven retrospective studies were selected for inclusion, including a total of 24, 203 patients who were recruited from 1989 to 2010 form Sweden, USA, and Germany."

"Local therapy for a primary tumour conferred a significantly better outcome in fit patients with oligometastatic prostate cancer at diagnosis. The evidence also suggests that radical prostatectomy is a preferable local therapy procedure for patients aged 65 years or younger or for those who have an AJCC stage M1a tumour."

-Patrick

ncbi.nlm.nih.gov/pubmed/279...

Lancet. 2016 Oct;388 Suppl 1:S84. doi: 10.1016/S0140-6736(16)32011-6.

Efficacy and safety of prostate-targeted local therapy in patients with newly diagnosed oligometastatic prostate cancer: a systematic review and meta-analysis.

Qiu S1, Yang L1, Deng L2, Liu L1, Han P1, Wei Q3.

Author information

Abstract

BACKGROUND:

The role of local therapy for the management of oligometastatic prostate cancer at diagnosis still remains poorly defined. We did a systematic review and meta-analysis evaluating local therapy of the primary tumour for patients with oligometastatic prostate cancer at diagnosis as well as the patients who can benefit the most.

METHODS:

For this systematic review, we searched PubMed, EMBASE, Medline, and the Cochrane Library for studies from database inception until March, 2016, for local therapy of the primary tumour in patients with oligometastatic prostate cancer. No language restrictions were applied. We estimated the risk of bias for the individual research studies using the Newcastle-Ottawa Scale (NOS). We assessed the publication bias using both the Egger's linear regression approach and funnel plots. The baseline characteristics on trial, patient, and treatment level were extracted. The primary outcomes were overall survival and disease-specific survival. All statistical analyses were performed using Stata v.12.0 software (StataCorp, College Station, TX, USA).

FINDINGS:

Seven retrospective studies were selected for inclusion, including a total of 24 203 patients who were recruited from 1989 to 2010 form Sweden, USA, and Germany. For overall survival, the pooled hazard ratio (HR) in patients treated with local therapy compared with no local therapy was 0·53 (95% CI 0·40-0·71; p <0·01). Local therapy was also associated with a 49% improvement of disease-specific survival (HR 0·51, 95% CI 0·37-0·69, p<0·01). This significant increase in disease-specific survival was better pronounced in patients younger (HR 0·34, 0·23-0·52, p<0·01) than 65 years than in those 65 years or older (HR 0·44, 0·28-0·68, p <0·01). The tumour-specific factor was associated with the improved survival in patients with AJCC (American Joint Committee on Cancer) M1a stage (HR 0·29, 0·18-0·48, p<0·01) than in those with M1b (HR 0·40, 0·24-0·68, p<0·001) and M1c (HR 0·34; 0·24-0·50, p<0·01).

INTERPRETATION:

Local therapy for a primary tumour conferred a significantly better outcome in fit patients with oligometastatic prostate cancer at diagnosis. The evidence also suggests that radical prostatectomy is a preferable local therapy procedure for patients aged 65 years or younger or for those who have an AJCC stage M1a tumour. We believe that important local therapy factors should be systematically assessed to develop a personalised approach to improve patient survival FUNDING: This study was supported by the Prostate Cancer Foundation Young Investigator Award 2013, the National Natural Science Foundation of China (81300627 and 81370855) and Programs from Science and Technology Department of Sichuan Province (2013SZ0006 and 2014JY0219).

Copyright © 2016 Elsevier Ltd. All rights reserved.

PMID: 27968903 DOI: 10.1016/S0140-6736(16)32011-6

[PubMed - in process]

[BigRich]

In 2003, after 72 Gy radiation in 1999 I had cryosurgery to the prostate. I hoped that nothing would show up on the scans, for even if I was not cured; I believed that debulking the primary tumor would extent my life. The Partin Table before my radiation: stated that there was only a 56% chance that the PCa was confinded to the orostate.

Rich

[Hidden]

One would think that eliminating the main tumor -- the source of shedding cancer cells that then take root in the process of metastasis -- would just be common sense. I've never understood the strategy of leaving the prostate tumor alone once metastasis is evident.

[pjoshea13 in reply to Hidden]

It's probably a combination of (a) wanting to spare the patient the morbidity of RP, & (b) an unrealistic reliance on ADT.

-Patrick

[JoelT in reply to Hidden]

Actually debunking A tumor remains a very controversial issue. One argument is that removing the main tumor does slow down the progression because there's just less material in the body.

The alternative argument that I've heard is that when one removes the main tumor the daughter cells, the distant metastases, going to high gear and continue the disease progression process at what some doctors believe is a higher level.

Unfortunately, neither of these theories have been proven.

Joel

[pjoshea13 in reply to JoelT]

I became convinced that debulking was desirable, when I began to read studies of the crosstalk between stromal & PCa cells. The stroma is not a benign presence in the intact prostate. Elimination via RP immediately removes unwanted communication with any PCa cells that might remain in the prostate bed.

[1] is an early example of what I mean.

"For the in vitro study, a three-dimensional co-culture system was used. It consisted of two layers of collagen gel. Stromal cells were suspended in the lower layer, whereas cancer cells were suspended in the upper layer. Compared to the control culture, the presence of P-ST {prostate-derived stromal} cells in the lower collagen layer significantly stimulated the growth of carcinoma cells."

"We identified hepatocyte growth factor (HGF) as the principal growth factor released by P-ST cells ... Neutralizing antibodies against HGF completely abrogated the stimulatory effect of P-ST cells."

[2] in the latest study, stromal cells can be induced to make androgens for cancer cells.

[3] a 2013 review paper states that:

"... most therapies are targeted towards the malignant epithelial cell component of the cancer and it should not be forgotten that cancer cells exist in close and symbiotic relationships with other components of the tumour. Paracrine and stromal signals are often critical to the growth of the cancer and represent new potential therapeutic targets that are separate from the malignant epithelial cells. The stroma produces numerous growth factors, including vascular endothelial growth factor family members, platelet-derived growth factors and fibroblast growth factors, which are all critical for tumour growth."

...

One could argue that the removal of stromal cells might make life difficult for surviving PCa cells, & that this might result in adaptations that make the cancer more difficult to manage. If that is the case, perhaps RP needs to be coupled with treatment that takes advantage of the disadvantaged cancer cells.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/109...

[2] ncbi.nlm.nih.gov/pubmed/276...

[3] ncbi.nlm.nih.gov/pubmed/238...

[Hidden in reply to JoelT]

After my biopsy and diagnosis I consulted with another urologist for a 2nd opinion. 1st and 2nd urologists nixed the idea of surgery since my prior TURP surgery made things dicey. 2nd urologist offered a more sensitive scan (conventional CT and bone scans were negative for metastasis) saying that if this scan came back positive all bets were off and that I'd get ADT only. Heck with that! I declined that test and ended up opting for HIFU. Why would I take a test that would jeopardize aggressive treatment?

[Hidden]

thanks. sent to my treating physician.