Surgical cytoreduction of the primary tumor reduces metastatic progression in a mouse model of prostate cancer

Cifuentes, Federico; Valenzuela, Rodrigo; Contreras, Héctor R.; Castellón, Enrique A.

doi:10.3892/or.2015.4319

Cited by 28 publications

(22 citation statements)

References 33 publications

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“…Several studies suggested an interaction between solid tumors, their circulating and disseminated tumor cells, and the development and maintenance of secondary lesions. In mouse models, it has been shown that the removal of the primary tumor may prevent the development of new metastasis 38 . The crucial interaction via a complex connecting network between the primary PCa, its host, and its distant metastases may justify how primary tumor ablation could lead to preventing the development of new metastases and, by analogy with other types of cancer, a regression of metastases or their disappearance.…”

Section: Role Of Primary Tumor Cytoreduction In Mcrpcmentioning

confidence: 99%

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study

Frantellizzi

Costa

Mascia

et al. 2020

Clinical Genitourinary Cancer

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MicroabstractThis study investigates the impact on the overall survival of previous radical primary treatment in mCRPC patients treated with 223-Ra. In this multicenter retrospective study, we enrolled 275 consecutive patients. Results obtained showed a clear advantage for patients subjected to radical primary treatment in respect of those without, with an estimated median survival of 18 months and 11, respectively. AbstractBackground. We provide an analysis aiming to investigate, in a real-life setting, the prognostic relevance of previous primary treatment (radical prostatectomy (RP) or external beam radiotherapy (EBRT)) in terms of overall survival, in mCRPC patients treated with 223-Ra. Materials and methodsIn this multicenter retrospective study we enrolled 275 consecutive patients. Demographics and clinical data, as well as mCRPC characteristics, have been obtained and evaluated at baseline and the end of the treatment or progression. 223-Ra has been administered according to the current label authorization until disease progression or unacceptable toxicity. We divided the whole cohort into 2 groups: men previously treated with primary radical prostatectomy or ablative radiotherapy (RP/EBRT) and patient with no prior primary treatment available (NO). Results128 out of 275 patients (46.5%) are alive and currently on follow-up; 103 patients (37.4%) dropped treatment out for disease progression or onset of comorbidities, and 147 patients died during the follow-up (53.5%). 93 patients underwent RP, 76 patients performed ablative EBRT. 132 patients enrolled in the RP/EBRT group (48%), 143 patients in the NO group (52%).Data showed a clear advantage for patients subjected to RP or EBRT in respect of those without primary treatment performed, with an estimated median survival of 18 months and 11 respectively (p<0.001). The multivariate analysis corroborated this trending results, returning in an HR of 0.7 (p-value= 0.0443), confirming the best outcome of the RP/EBRT group. 3 Conclusions Previous radical treatment plays a protective role in mCRPC patients who underwent 223-Ra treatment.

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Section: Role Of Primary Tumor Cytoreduction In Mcrpcmentioning

confidence: 99%

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study

Frantellizzi

Costa

Mascia

et al. 2020

Clinical Genitourinary Cancer

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“…Cancer progresses in a stepwise fashion. Despite limited data regarding the role of aggressive local therapy in advanced prostate cancer, current studies suggest that local treatment decreases the tumor burden and increases the time required for castration-resistant prostate cancer (CRPC) to develop [9,10]. Tumor burden is one of the best predictors of long-term outcomes of prostate cancer [11,12,13].…”

Section: Introductionmentioning

confidence: 99%

Effect of Tumor Burden on Tumor Aggressiveness and Immune Modulation in Prostate Cancer: Association with IL-6 Signaling

Huang

Chen

et al. 2019

Cancers

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Local treatment is known to improve survival in men with locally advanced prostate cancer (LAPC), but the underlying mechanisms remain unclear. In the present study, we examined the role of tumor burden in tumor aggressiveness, as well as the pathway responsible for these changes. We used human and murine prostate cancer cell lines to examine the role of tumor burden in tumor aggressiveness, as well as its correlation with cancer stem cell (CSC) marker levels and IL-6 signaling. Furthermore, 167 prostate cancer biopsy specimens were analyzed in terms of correlations of IL-6 and CD44 levels with clinical patient characteristics. Data from preclinical models showed that larger tumor burden was associated with more aggressive tumor growth associated and increased CD44 expression. Using cellular experiments and orthotopic tumor models, we showed that CD44+ prostate cancer cells have CSC-like properties, enhanced epithelial–mesenchymal transition (EMT), and a more immunosuppressive microenvironment. There was a significant correlation between IL-6 and CD44 levels based on in vitro testing of clinical samples. Blockade of IL-6/STAT3 signaling attenuated the expression of CD44, CSC-like properties, and aggressive tumor behavior in vitro and in vivo. In conclusion, CD44 expression is significantly associated with tumor aggressiveness in prostate cancer and activation of IL-6 signaling leads to a suitable microenvironment for the induction of CD44 expression. Based on our study, reduced tumor burden was associated with attenuated IL-6 signaling and augmented tumor rejection in the microenvironment, which might mediate the benefit of clinical adoption with aggressive local therapy.

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“…The ‘premetastatic niche’ theory put forward by Kaplan et al demonstrated that the primary tumor could act as the predominant source of metastasis through circulating tumor cells [ 6 ]. The following mouse models by Cifuentes et al verified the theory that by removal of the primary tumor, the development of new metastasis could be prevented [ 7 ]. Meanwhile, several studies had successfully confirmed the benefit of cytoreductive surgery for other metastatic malignancy such as renal and ovarian cancers [ 8 , 9 ] and in which two aspects of the role highlighted, reducing the overall tumor burden and interrupting the re-seeding of the primary tumor [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

The role of radical prostatectomy for the treatment of metastatic prostate cancer: a systematic review and meta-analysis

et al. 2018

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The recommended therapy by EAU guidelines for metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT) with or without chemotherapy. The role of radical prostatectomy (RP) in the treatment of mPCa is still controversial. Hence, a meta-analysis was conducted by comprehensively searching the databases PubMed, EMBASE and Web of Science for the relevant studies published before September 1st, 2017. Our results successfully shed light on the relationship that RP for mPCa was associated with decreased cancer-specific mortality (CSM) (pooled HR = 0.41, 95%CI = 0.36–0.47) and enhanced overall survival (OS) (pooled HR = 0.49, 95%CI = 0.44–0.55). Subsequent stratified analysis demonstrated that no matter how RP compared with no local therapy (NLT) or radiation therapy (RT), it was linked to a lower CSM (pooled HR = 0.36, 95%CI = 0.30–0.43 and pooled HR = 0.56, 95%CI 0.43–0.73, respectively) and a higher OS (pooled HR = 0.49, 95%CI = 0.44–0.56 and pooled HR = 0.46, 95%CI 0.33–0.65, separately). When comparing different levels of Gleason score, M-stage or N-stage, our results indicated that high level of Gleason score, M-stage or N-stage was associated with increased CSM. In summary, the outcomes of the present meta-analysis demonstrated that RP for mPCa was correlated with decreased CSM and enhanced OS in eligible patients of involved studies. In addition, patients with less aggressive tumors and good general health seemed to benefit the most. Moreover, no matter compared with NLT or RT, RP showed significant superiority in OS or CSM. Upcoming prospective randomized controlled trials were warranted to provide more high-quality data.

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Surgical cytoreduction of the primary tumor reduces metastatic progression in a mouse model of prostate cancer

Cited by 28 publications

References 33 publications

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study

Effect of Tumor Burden on Tumor Aggressiveness and Immune Modulation in Prostate Cancer: Association with IL-6 Signaling

The role of radical prostatectomy for the treatment of metastatic prostate cancer: a systematic review and meta-analysis

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