Tumour and immune cell dynamics explain the PSA bounce after prostate cancer brachytherapy

Yamamoto, Yoichiro; Offord, Chetan P.; Kimura, Go; Kuribayashi, Shigehiko; Takeda, Hayato; Tsuchiya, Shin-ichi; Shimojo, Hisashi; Kanno, Hiroyuki; Božić, Ivana; Nowak, Martin A.; Bajzer, Željko; Dingli, David

doi:10.1038/bjc.2016.171

Cited by 38 publications

(29 citation statements)

References 33 publications

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“…The mechanisms underlying PSA bounce and its association with age have not been fully elucidated. However, Yamamoto et al demonstrated an increase in tumor-infiltrative CD3 and cytotoxic CD8 cells in bounce-positive patients [18], seemingly explaining the higher incidence of PSA bounce in younger (i.e., more immunocompetent) patients.…”

Section: Discussionmentioning

confidence: 99%

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Kinetics of Prostate-Specific Antigen after Carbon Ion Radiotherapy for Prostate Cancer

Darwis

Oike

Kawamura

et al. 2020

Cancers

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This study aimed to first elucidate prostate-specific antigen (PSA) kinetics in prostate cancer patients treated with carbon ion radiotherapy (CIRT). From 2010 to 2015, 131 patients with prostate adenocarcinoma treated with CIRT (57.6 Gy relative biological effectiveness (RBE) in 16 fractions) alone were recruited. PSA was measured at 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 months post-CIRT. PSA bounce was defined as PSA increase over a cutoff followed by spontaneous decrease to or below the pre-bounce nadir. PSA failure was determined using the Phoenix criteria (nadir + 2.0 ng/mL). As a result, non-failure-associated temporary increase in PSA exhibited two distinct patterns, namely a classical bounce and a surge at one month. PSA bounce of ≥0.2 ng/mL was observed in 55.7% of the patients. Bounce amplitude was <2.0 ng/mL in 97.6% of cases. Bounce occurred significantly earlier than PSA failure. Younger age was a significant predictor of bounce occurrence. Bounce positivity was a significant predictor of favorable 5-year PSA failure-free survival. Meanwhile, a PSA surge of ≥0.2 ng/mL was observed in 67.9% of patients. Surge amplitude was significantly larger than bounce amplitude. Larger prostate volume was a significant predictor of PSA surge occurrence. PSA surge positivity did not significantly predict PSA failure. In summary, PSA bounce was distinguishable from PSA failure with regard to timing of occurrence and amplitude (earlier and lower for bounce, respectively). These data are useful for post-CIRT surveillance of prostate cancer patients.

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Section: Discussionmentioning

confidence: 99%

“…CIRT was initiated on day 0. PSA was measured at 1,2,3,6,9,12,15,18,21,24,30,36,42,48,54, and 60 months post-CIRT at Gunma University Hospital. PSA bounce was defined as an increase in PSA over a cutoff followed by a spontaneous decrease to or below the pre-bounce nadir [17].…”

Section: Psa Assessmentmentioning

confidence: 99%

Kinetics of Prostate-Specific Antigen after Carbon Ion Radiotherapy for Prostate Cancer

Darwis

Oike

Kawamura

et al. 2020

Cancers

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“…Spatial distribution of cytotoxic T cells in proximity to cancer cells has just recently been demonstrated to correlate with increased overall survival of patients with pancreatic cancer . Like the dynamics of immune reaction against tumors, infiltration of immune cells into tumors takes place . Hettich and colleagues demonstrated that irradiation with 2×12 Gy on consecutive days of B16 melanoma tumors induces a high infiltration of CD8+ T cells at day 5 after the last irradiation.…”

Section: Immunological Basis For Design Of Multimodal Radio‐immunothementioning

confidence: 99%

“…131 Like the dynamics of immune reaction against tumors, 132 infiltration of immune cells into tumors takes place. 133 Hettich and colleagues demonstrated that irradiation with 2×12 Gy on consecutive days of B16 melanoma tumors induces a high infiltration of CD8+ T cells at day 5 after the last irradiation. The presence of the cytotoxic T cells in the tumor was, however, limited since later on the amount of these adaptive immune cells dropped again.…”

Section: Dynamics Of Immune Cell Infiltrationmentioning

confidence: 99%

Immunomodulation by ionizing radiation—impact for design of radio‐immunotherapies and for treatment of inflammatory diseases

Frey

Rückert

Deloch

et al. 2017

Immunological Reviews

149

127

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Ionizing radiation is often regarded as an element of danger. But, danger responses on the cellular and molecular level are often beneficial with regard to the induction of anti-tumor immunity and for amelioration of inflammation. We outline how in dependence of radiation dose and fraction, radiation itself-and especially in combination with immune modulators-impacts on the innate and adaptive immune system. Focus is set on radiation-induced changes of the tumor cell phenotype and the cellular microenvironment including immunogenic cancer cell death. Mechanisms how anti-tumor immune responses are triggered by radiotherapy in combination with hyperthermia, inhibition of apoptosis, the adjuvant AnnexinA5, or vaccination with high hydrostatic pressure-killed autologous tumor cells are discussed. Building on this, feasible multimodal radio-immunotherapy concepts are reviewed including overcoming immune suppression by immune checkpoint inhibitors and by targeting TGF-β. Since radiation-induced tissue damage, inflammation, and anti-tumor immune responses are interconnected, the impact of lower doses of radiation on amelioration of inflammation is outlined. Closely meshed immune monitoring concepts based on the liquid biopsy blood are suggested for prognosis and prediction of cancer and non-cancer inflammatory diseases. Finally, challenges and visions for the design of cancer radio-immunotherapies and for treatment of benign inflammatory diseases are given.

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“…Although a treatment failure is traditionally defined using prostate specific antigen (PSA) through the Phoenix criteria as the nadir þ 2 ng/mL, a phenomenon was observed after brachytherapy in which a nonfailure interval PSA climbs by a value less than 2 ng/mL and then returns to the prerise PSA or below, which was coined by Wallner as PSA ''bounce.'' (9) Although the exact pathophysiologic significance of the bounce phenomenon is unclear, recent evidence suggests that it may be related to an increased T-cell response to the tumor (10). Several studies have analyzed the predictive and prognostic significance of the PSA bounce.…”

Section: Introductionmentioning

confidence: 99%

Racial differences in the PSA bounce in predicting prostate cancer outcomes after brachytherapy: Evidence from the Department of Veterans Affairs

2020

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PURPOSE: African American men have historically had poorer prostate cancer biochemical and survival outcomes than Caucasians. However, emerging data suggest nononcologic factors drive much of this disparity. Prior evidence has suggested an association between a transient prostate specific antigen (PSA) bounce and improved biochemical control. However, racial differences in this relationship have remained relatively unexplored. METHODS AND MATERIALS: We identified 4477 men treated for low-or intermediate-risk prostate cancer within the U.S. Department of Veterans Affairs (VA) from 2000 to 2010 with brachytherapy alone or in combination with external beam radiotherapy without androgen deprivation. Longitudinal PSA data were used to define to biochemical failure and PSA bounce. Cox proportional hazard models were used explore racial differences in the relationship between the PSA bounce and time to biochemical failure. RESULTS: Thirty-one percent of our sample experienced a PSA bounce, with African Americans more likely to experience a bounce (42%) compared with Caucasians (29%); p !0.001. Despite this, African Americans had a higher likelihood of biochemical failure (hazard ratio [HR] 1.4; p 5 0.006). However, African American men experiencing a PSA bounce were less likely to experience a biochemical failure (HR 5 0.64; p 5 0.046), whereas this relationship was not statistically significant for Caucasians (HR 5 0.78; p 5 0.092). On multivariate analysis, African Americans receiving brachytherapy alone were most sensitive to the protective benefit of the PSA bounce (HR 5 0.64). CONCLUSIONS: A PSA bounce was associated with improved biochemical control among patients receiving brachytherapy as part of their treatment for low-or intermediate-risk prostate cancer at the VA. African American men treated with brachytherapy had a particularly pronounced biochemical control benefit of a PSA bounce.

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Tumour and immune cell dynamics explain the PSA bounce after prostate cancer brachytherapy

Cited by 38 publications

References 33 publications

Kinetics of Prostate-Specific Antigen after Carbon Ion Radiotherapy for Prostate Cancer

Kinetics of Prostate-Specific Antigen after Carbon Ion Radiotherapy for Prostate Cancer

Immunomodulation by ionizing radiation—impact for design of radio‐immunotherapies and for treatment of inflammatory diseases

Racial differences in the PSA bounce in predicting prostate cancer outcomes after brachytherapy: Evidence from the Department of Veterans Affairs

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