Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer; Report From the 2016 Coffey–Holden Prostate Cancer Academy Meeting

Miyahira, Andrea K.; Roychowdhury, Sameek; Goswami, Sangeeta; Ippolito, Joseph E.; Priceman, Saul J.; Pritchard, Colin C.; Sfanos, Karen S.; Subudhi, Sumit K.; Simons, Jonathan W.; Pienta, Kenneth J.; Soule, Howard R.

doi:10.1002/pros.23260

Cited by 8 publications

(9 citation statements)

References 173 publications

(202 reference statements)

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“…Aside from these rare cases with mismatch DNA repair defects, prostate cancer is considered to have a relatively immunologically “cold” microenvironment compared to other solid tumor types ( 15 , 16 ), however the relationship between lymphocytic infiltration and patient outcomes has varied widely in the literature ( 17 – 24 ). A few studies have suggested that low numbers of tumor-infiltrating lymphocytes are associated with a higher risk of disease progression ( 17 , 21 ), while most other studies have shown the opposite ( 18 – 21 , 23 , 24 ).…”

Section: Introductionmentioning

confidence: 99%

Association of tumor-infiltrating T-cell density with molecular subtype, racial ancestry and clinical outcomes in prostate cancer

Kaur

Guedes

et al. 2018

Modern Pathology

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The inflammatory microenvironment plays an important role in the pathogenesis and progression of tumors and may be associated with somatic genomic alterations. We examined the association of tumor infiltrating T-cell density with clinical-pathologic variables, tumor molecular subtype and oncologic outcomes in surgically-treated primary prostate cancer occurring in patients of European-American or African-American ancestry. We evaluated 312 primary prostate tumors, enriched for patients with African-American ancestry and high grade disease. Tissue microarrays were immunostained for CD3, CD8 and FOXP3 and were previously immunostained for ERG and PTEN using genetically validated protocols. Image analysis for quantification of T-cell density in tissue microarray tumor spots was performed. Automated quantification of T-cell densities in tumor-containing regions of tissue microarray spots and standard histologic sections were correlated (r=0.73, p<0.00001) and there was good agreement between visual and automated T-cell density counts on tissue microarray spots (r=0.93, p<0.00001). There was a significant correlation between CD3+, CD8+ and FOXP3+ T-cell densities (p<0.00001), but these were not associated with most clinical or pathologic variables. Increased T-cell density was significantly associated with ERG positivity (median 309 vs 188 CD3+ T-cells/mm2; p=0.0004) and also with PTEN loss (median 317 vs 192 CD3+ T-cells/mm2; p=0.001) in the combined cohort of matched European-American and African-American ancestry patients. The same association or a similar trend was present in patients of both ancestries when analyzed separately. When the African-American patients from the matched race set were combined with a separate high grade set of African-American cases, there was a weak association of increased FOXP3+ T-cell densities with increased risk of metastasis in multivariable analysis. Though high T-cell density is associated with specific molecular subclasses of prostate cancer, we did not find an association of T-cell density with racial ancestry.

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Section: Introductionmentioning

confidence: 99%

Association of tumor-infiltrating T-cell density with molecular subtype, racial ancestry and clinical outcomes in prostate cancer

Kaur

Guedes

et al. 2018

Modern Pathology

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“…Interestingly, three quarters of patients recurring following SBRT to bone-only disease reoccurred in bone, whilst irradiated nodal disease re-occurred only in other nodes. This predilection for recurrence locations manifests the interaction between cancer biology and its microenvironment, a concept described as seed and soil (93). A recent retrospective study of prophylactic nodal treatment found that elective nodal radiotherapy +/− boost, reduces nodal recurrences compared to SBRT (P<0.001), and for patients with a single node this led to a significantly longer metastases-free survival (P=0.009; HR 0.5, 95% CI, 0.3-0.85) (94).…”

Section: Early Datamentioning

confidence: 99%

A narrative review of oligometastatic prostate cancer—an evolving paradigm

Sritharan¹,

Rieu²,

Tree³

2021

Ann Palliat Med

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There has been growing interest in oligometastatic prostate cancer (OMPC) with a mounting body of evidence to suggest that it is a distinct disease state, both biologically and prognostically, when compared to polymetastatic prostate cancer. Three subgroups have been recognised; de novo synchronous, metachronous/oligorecurrent and oligoprogressive disease. The belief that patients with OMPC can be treated more aggressively to improve survival is transforming patient care. Identifying these patients poses the first challenge, and we explore the imaging modalities currently utilised and those that are promising. For patients with de novo synchronous OMPC, both early systemic treatment in addition to androgen deprivation therapy (ADT) and radiotherapy to the prostate increase overall survival (OS), and both are increasingly being integrated into routine clinical practice. Metastasis-directed therapy (MDT) has predominantly been delivered using stereotactic body radiotherapy (SBRT) in prostate cancer and studies have shown SBRT is well-tolerated, provides excellent local control and can be used to delay ADT in the metachronous setting. We discuss the current management strategies in OMPC, review the evidence supporting the use of SBRT and outline ongoing trials.

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“…For six consecutive years, PCF has convened the Coffey‐Holden Prostate Cancer Academy (CHPCA) Meeting, an annual “think tank” conference, which gathers ∼75 investigators to discuss the most critical topics necessary for making a near‐term impact on the understanding and treatment of lethal prostate cancer . This meeting is uniquely designed to promote deep and ample discussion and brainstorming of necessary next steps by structuring sessions into short talks with lengthy discussion times.…”

Section: Introductionmentioning

confidence: 99%

Tumor cell heterogeneity and resistance; report from the 2018 Coffey‐Holden Prostate Cancer Academy Meeting

Miyahira

Den²,

Carlo³

et al. 2018

The Prostate

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Introduction The 2018 Coffey‐Holden Prostate Cancer Academy (CHPCA) Meeting, “Tumor Cell Heterogeneity and Resistance,” was held in Los Angeles, California from June 21 to 24, 2018. Methods The CHPCA Meeting is a unique, discussion‐oriented scientific conference convened annually by the Prostate Cancer Foundation (PCF), which focuses on the most critical topics in need of further study to advance the treatment of lethal prostate cancer. The 6th Annual CHPCA Meeting was attended by 70 investigators and concentrated on prostate cancer heterogeneity and treatment resistance. Results The meeting focused on topics including: recognition of tumor heterogeneity, molecular drivers of heterogeneity, the role of the tumor microenvironment, the role of heterogeneity in disease progression, metastasis and treatment resistance, clinical trials designed to target resistance and tumor heterogeneity, and immunotherapeutic approaches to target and overcome tumor heterogeneity. Discussion This review article summarizes the presentations and discussions from the 2018 CHPCA Meeting in order to share this knowledge with the scientific community and encourage new studies that will lead to improved treatments and outcomes for men with prostate cancer.

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Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer; Report From the 2016 Coffey–Holden Prostate Cancer Academy Meeting

Cited by 8 publications

References 173 publications

Association of tumor-infiltrating T-cell density with molecular subtype, racial ancestry and clinical outcomes in prostate cancer

Association of tumor-infiltrating T-cell density with molecular subtype, racial ancestry and clinical outcomes in prostate cancer

A narrative review of oligometastatic prostate cancer—an evolving paradigm

Tumor cell heterogeneity and resistance; report from the 2018 Coffey‐Holden Prostate Cancer Academy Meeting

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