Impact of Cerebrovascular Disease on Survival Benefits from Local Treatment in Patients with De Novo Metastatic Hormone-Sensitive PCa.

[pjoshea13]

New Korean study below [1].

Basically, is there a survival advantage in having local treatment when diagnosed with metastatic PCa?

"In the overall cohort and in patients without a history of CVD, patients who underwent local treatment exhibited higher {overall survival } than men who received ADT alone ..."

"... the survival benefit conferred by local treatment was not seen in patients with a history of CVD ..."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/317...

Yonsei Med J. 2019 Dec;60(12):1129-1137. doi: 10.3349/ymj.2019.60.12.1129.

Impact of Cerebrovascular Disease on Survival Benefits from Local Treatment in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer.

Kim TJ1, Yu YD1, Park DS1, Rha KH2, Hong SJ2, Cho KS3, Chung BH3, Koo KC4.

Author information

1

Department of Urology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.

2

Department of Urology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

3

Department of Urology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

4

Department of Urology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. [e-mail].

Abstract

PURPOSE:

Local treatment has become a treatment option for patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). Subgroup analyses based on a history of cerebrovascular disease (CVD) were performed to evaluate the impact thereof on overall survival (OS) after local treatment.

MATERIALS AND METHODS:

A retrospective analysis was performed for 879 patients with de novo mHSPC between August 2003 and November 2016. Patients were stratified according to prior CVD history and the type of initial treatment: androgen-deprivation therapy (ADT) alone versus local treatment consisting of radical prostatectomy (RP) or radiation therapy (RT) with ADT, with or without metastasis-directed therapy. The primary outcome was OS assessed by Kaplan-Meier analysis and Cox-regression models.

RESULTS:

Of 879 patients, 660 (75.1%) men underwent ADT alone, and 219 (24.9%) men underwent RP or RT with ADT, with or without metastasis-directed therapy. The median follow-up was 38 months. Multivariable analysis showed CVD history to be associated with a higher risk of overall mortality (p=0.001). In the overall cohort and in patients without a history of CVD, patients who underwent local treatment exhibited higher OS than men who received ADT alone (all p<0.001). However, the survival benefit conferred by local treatment was not seen in patients with a history of CVD (p=0.324). OS was comparable between patients who received RP and RT (p=0.521).

CONCLUSION:

Local treatment with or without metastasis-directed therapy may provide OS advantages for mHSPC patients without a history of CVD. Further prospective studies are needed to address these important concerns.

© Copyright: Yonsei University College of Medicine 2019.

KEYWORDS:

Cerebrovascular disorders; neoplasm metastasis; prostatic neoplasms; survival

PMID: 31769243 DOI: 10.3349/ymj.2019.60.12.1129

[cesces]

"However, the survival benefit conferred by local treatment was not seen in patients with a history of CVD"

This seems a bit confusing and complicated. It seems like there's a lot going on here.

Seems like this exception to the general rule may be limited to patients with pre-existing CV?

[pjoshea13 in reply to cesces]

Does it imply that any benefit from local treatment is countered by treatment morbidity in men with CVD?

-Patrick

[cesanon in reply to pjoshea13]

"Does it imply that any benefit from local treatment is countered by treatment morbidity in men with CVD?"

Actually it doesn't say that. CVD patients had slightly higher overall morbidity, which I guess should be expected. But their morbidity was about the same with ADT alone or with ADT and local treatment (both prostatectomy or radiation therapy)

Very confusing. Very non-intuitive.

==============================

"There has been a paradigm shift in considering local treatments targeted at both the primary tumor and metastatic lesions in patients with mHSPC and limited metastatic burden.6

However, there is no guideline on which subgroup of patients for whom such aggressive treatments may confer a survival benefit. We observed an OS benefit with local treatment of the primary tumor in patients regardless of the metastatic burden.

However, the survival benefit with local treatment was not seen in patients with a prior history of CVD. These findings suggest that comorbidities are crucial factors that affect the survival benefit of local treatment in patients with mHSPC.

The biological definition of oligometastatic PCa remains debatable, and advances in imaging techniques are shifting the treatment paradigm of this disease entity.

Various studies have proposed different definitions regarding the number and sites of metastatic lesions to define oligometastatic PCa based on oncological outcomes.11,12

The definition regarding the cut-off number of metastatic lesions is yet controversial, and for now, this disease entity should only be interpreted as a disease state between the presence of intravascular circulating tumor cells and disseminated metastasis.13,14

Existing studies regarding oligometastatic PCa exclude patients with underlying comorbidities, such as CVD.15-19 Our study cohort included patients with initially diagnosed mHSPC regardless of the number of metastatic lesions and comorbidities, and there was no significant difference in metastatic burden between the ADT alone and ADT with local treatment groups.

In an attempt to identify a subset of patients who would benefit from local treatment of mHSPC, our study suggests that the number of metastatic lesions may not be the most significant indicator for predicting a survival benefit with local treatment. Our study showed that CVD, followed by Gleason score, was the strongest prognosticator of OS. Several hypotheses can be offered.

First, the detrimental effect of CVD on OS may have offset the beneficial effect of local treatment, in addition to well known prognostic factors, such as Gleason score and tumor stage. CVD is known to be significantly associated with survival, with a 0.15-year loss of life expectancy in the aged population.20 It has been reported that the risk of thromboembolic disease increases as cancer stage increases.21 Babiker, et al.22 showed that the early release of prostasomes originating from PCa cells into the bloodstream evokes coagulation effects resulting in an increased risk of thromboembolism. Brain injury resulting from vascular pathology can also activate the coagulation cascade, causing a state of hypercoagulability with the release of thromboplastin-like factors from the central nervous system.23

In summary, a history of CVD, which indicates pathological hemostatic changes, may contribute to the disease course and OS outcomes.

Future studies are warranted to identify the underlying pathophysiology of CVD in the PCa microenvironment.

Second, the administration of continuous ADT may exacerbate CVD and its disease course. ADT increases coagulation disorders that are related to a complex interplay of factors, including procoagulant factors released by tumor and/or host blood vessels.22 Hypercoagulability is common in cancer patients, and hence, it is reasonable to consider that ADT serves as an aggravator of CVD and inferior OS outcomes. Our results imply that comorbidities, especially CVD, are potential risk factors to be accounted for when considering local treatments in addition to ADT for patients with mHSPC

21. Nanda A, Chen MH, Braccioforte MH, Moran BJ, D’Amico AV. Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction. JAMA 2009;302:866-73.

22. Babiker AA, Ekdahl KN, Nilsson B, Ronquist G. Prothrombotic effects of prostasomes isolated from prostatic cancer cell lines and seminal plasma. Semin Thromb Hemost 2007;33:80-6.

23. Kaur H, Siemens DR, Black A, Robb S, Barr S, Graham CH, et al. Effects of androgen-deprivation therapy on hypercoagulability in prostate cancer patients: a prospective, longitudinal study. Can Urol Assoc J 2017;11:33-8.

eymj.org/Synapse/Data/PDFDa...