Impact of Biochemical Failure After Salvage Radiation Therapy on Prostate Cancer-specific Mortality

Competition Between Age and Time to Biochemical Failure

William C. Jackson, Krithika Suresh, Vasu Tumati, Robert T. Dess, Payal D. Soni, Shuang G. Zhao, Zachary S. Zumsteg, Raquibul Hannan, Brent K. Hollenbeck, Arvin George, Samuel D. Kaffenberger, Simpa S. Salami, Jason W.D. Hearn, Todd M. Morgan, Rohit Mehra, Matthew Schipper, Felix Y. Feng, Neil B Desai, Daniel E. Spratt

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND: Disease progression following salvage radiotherapy (SRT) for prostate cancer (PC) is common, and the time to biochemical recurrence (BCR) is heterogeneous. OBJECTIVE: To describe the temporal distribution and clinical impact of BCR following SRT and model outcomes using patient age and time to BCR from SRT. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multi-institutional study included 547 consecutive men with lymph node-negative PC receiving SRT from 1985 to 2013. The median follow-up after SRT was 8.4 yr. Intervention All men received SRT with three-dimensional or intensity-modulated RT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: BCR was defined as a rise in prostate-specific antigen (PSA) ≥0.2ng/ml above the PSA nadir followed by a sequentially equal or higher value. Additional outcomes included distant metastasis (DM), PC-specific mortality (PCSM), and overall mortality (OM). Cox proportional hazards models, a landmark analysis, and comparison of c-indices were used. Cumulative incidence curves were estimated from a Fine and Gray regression model. RESULTS AND LIMITATIONS: The estimated 10-yr cumulative incidence of BCR was 60%. Of the 274 men experiencing BCR, 149 (54%) had BCR within 18 mo of SRT. BCR ≤18 mo after SRT was associated with a higher risk of DM (hazard ratio [HR] 7.44, 95% confidence interval [CI] 4.91-11.3; p<0.001), PCSM (HR 12.3, 95% CI 5.95-25.2; p<0.001), and OM (HR 2.85, 95% CI 1.94-4.17; p<0.001). We provide a model to estimate the cumulative incidence of DM and PCSM using age and time to BCR. The retrospective nature of our analysis limits our findings. CONCLUSIONS: A strikingly large proportion of men experience early BCR following SRT and are at higher risk of DM and PCSM. Novel predictive biomarkers are needed to identify men harboring micrometastatic disease to avoid potentially futile local therapies or allow for intensification of systemic therapies. PATIENT SUMMARY: Many men will develop biochemical recurrence of prostate cancer after salvage radiotherapy. Men with biochemical recurrence within 18 mo of salvage radiotherapy constitute a cohort at higher risk of distant metastasis and prostate cancer-specific mortality.

Original languageEnglish (US)
Pages (from-to)276-282
Number of pages7
JournalEuropean urology oncology
Volume1
Issue number4
DOIs
StatePublished - Sep 1 2018

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Salvage Therapy
Prostatic Neoplasms
Radiotherapy
Recurrence
Mortality
Neoplasm Metastasis
Confidence Intervals
Prostate-Specific Antigen
Incidence
Hospital Distribution Systems
Proportional Hazards Models
Disease Progression
Biomarkers

Keywords

  • Biochemical failure
  • Postprostatectomy
  • Salvage radiation therapy

Cite this

Impact of Biochemical Failure After Salvage Radiation Therapy on Prostate Cancer-specific Mortality : Competition Between Age and Time to Biochemical Failure. / Jackson, William C.; Suresh, Krithika; Tumati, Vasu; Dess, Robert T.; Soni, Payal D.; Zhao, Shuang G.; Zumsteg, Zachary S.; Hannan, Raquibul; Hollenbeck, Brent K.; George, Arvin; Kaffenberger, Samuel D.; Salami, Simpa S.; Hearn, Jason W.D.; Morgan, Todd M.; Mehra, Rohit; Schipper, Matthew; Feng, Felix Y.; Desai, Neil B; Spratt, Daniel E.

In: European urology oncology, Vol. 1, No. 4, 01.09.2018, p. 276-282.

Research output: Contribution to journalArticle

Jackson, WC, Suresh, K, Tumati, V, Dess, RT, Soni, PD, Zhao, SG, Zumsteg, ZS, Hannan, R, Hollenbeck, BK, George, A, Kaffenberger, SD, Salami, SS, Hearn, JWD, Morgan, TM, Mehra, R, Schipper, M, Feng, FY, Desai, NB & Spratt, DE 2018, 'Impact of Biochemical Failure After Salvage Radiation Therapy on Prostate Cancer-specific Mortality: Competition Between Age and Time to Biochemical Failure', European urology oncology, vol. 1, no. 4, pp. 276-282. https://doi.org/10.1016/j.euo.2018.04.014
Jackson, William C. ; Suresh, Krithika ; Tumati, Vasu ; Dess, Robert T. ; Soni, Payal D. ; Zhao, Shuang G. ; Zumsteg, Zachary S. ; Hannan, Raquibul ; Hollenbeck, Brent K. ; George, Arvin ; Kaffenberger, Samuel D. ; Salami, Simpa S. ; Hearn, Jason W.D. ; Morgan, Todd M. ; Mehra, Rohit ; Schipper, Matthew ; Feng, Felix Y. ; Desai, Neil B ; Spratt, Daniel E. / Impact of Biochemical Failure After Salvage Radiation Therapy on Prostate Cancer-specific Mortality : Competition Between Age and Time to Biochemical Failure. In: European urology oncology. 2018 ; Vol. 1, No. 4. pp. 276-282.
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abstract = "BACKGROUND: Disease progression following salvage radiotherapy (SRT) for prostate cancer (PC) is common, and the time to biochemical recurrence (BCR) is heterogeneous. OBJECTIVE: To describe the temporal distribution and clinical impact of BCR following SRT and model outcomes using patient age and time to BCR from SRT. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multi-institutional study included 547 consecutive men with lymph node-negative PC receiving SRT from 1985 to 2013. The median follow-up after SRT was 8.4 yr. Intervention All men received SRT with three-dimensional or intensity-modulated RT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: BCR was defined as a rise in prostate-specific antigen (PSA) ≥0.2ng/ml above the PSA nadir followed by a sequentially equal or higher value. Additional outcomes included distant metastasis (DM), PC-specific mortality (PCSM), and overall mortality (OM). Cox proportional hazards models, a landmark analysis, and comparison of c-indices were used. Cumulative incidence curves were estimated from a Fine and Gray regression model. RESULTS AND LIMITATIONS: The estimated 10-yr cumulative incidence of BCR was 60{\%}. Of the 274 men experiencing BCR, 149 (54{\%}) had BCR within 18 mo of SRT. BCR ≤18 mo after SRT was associated with a higher risk of DM (hazard ratio [HR] 7.44, 95{\%} confidence interval [CI] 4.91-11.3; p<0.001), PCSM (HR 12.3, 95{\%} CI 5.95-25.2; p<0.001), and OM (HR 2.85, 95{\%} CI 1.94-4.17; p<0.001). We provide a model to estimate the cumulative incidence of DM and PCSM using age and time to BCR. The retrospective nature of our analysis limits our findings. CONCLUSIONS: A strikingly large proportion of men experience early BCR following SRT and are at higher risk of DM and PCSM. Novel predictive biomarkers are needed to identify men harboring micrometastatic disease to avoid potentially futile local therapies or allow for intensification of systemic therapies. PATIENT SUMMARY: Many men will develop biochemical recurrence of prostate cancer after salvage radiotherapy. Men with biochemical recurrence within 18 mo of salvage radiotherapy constitute a cohort at higher risk of distant metastasis and prostate cancer-specific mortality.",
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TY - JOUR

T1 - Impact of Biochemical Failure After Salvage Radiation Therapy on Prostate Cancer-specific Mortality

T2 - Competition Between Age and Time to Biochemical Failure

AU - Jackson, William C.

AU - Suresh, Krithika

AU - Tumati, Vasu

AU - Dess, Robert T.

AU - Soni, Payal D.

AU - Zhao, Shuang G.

AU - Zumsteg, Zachary S.

AU - Hannan, Raquibul

AU - Hollenbeck, Brent K.

AU - George, Arvin

AU - Kaffenberger, Samuel D.

AU - Salami, Simpa S.

AU - Hearn, Jason W.D.

AU - Morgan, Todd M.

AU - Mehra, Rohit

AU - Schipper, Matthew

AU - Feng, Felix Y.

AU - Desai, Neil B

AU - Spratt, Daniel E.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - BACKGROUND: Disease progression following salvage radiotherapy (SRT) for prostate cancer (PC) is common, and the time to biochemical recurrence (BCR) is heterogeneous. OBJECTIVE: To describe the temporal distribution and clinical impact of BCR following SRT and model outcomes using patient age and time to BCR from SRT. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multi-institutional study included 547 consecutive men with lymph node-negative PC receiving SRT from 1985 to 2013. The median follow-up after SRT was 8.4 yr. Intervention All men received SRT with three-dimensional or intensity-modulated RT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: BCR was defined as a rise in prostate-specific antigen (PSA) ≥0.2ng/ml above the PSA nadir followed by a sequentially equal or higher value. Additional outcomes included distant metastasis (DM), PC-specific mortality (PCSM), and overall mortality (OM). Cox proportional hazards models, a landmark analysis, and comparison of c-indices were used. Cumulative incidence curves were estimated from a Fine and Gray regression model. RESULTS AND LIMITATIONS: The estimated 10-yr cumulative incidence of BCR was 60%. Of the 274 men experiencing BCR, 149 (54%) had BCR within 18 mo of SRT. BCR ≤18 mo after SRT was associated with a higher risk of DM (hazard ratio [HR] 7.44, 95% confidence interval [CI] 4.91-11.3; p<0.001), PCSM (HR 12.3, 95% CI 5.95-25.2; p<0.001), and OM (HR 2.85, 95% CI 1.94-4.17; p<0.001). We provide a model to estimate the cumulative incidence of DM and PCSM using age and time to BCR. The retrospective nature of our analysis limits our findings. CONCLUSIONS: A strikingly large proportion of men experience early BCR following SRT and are at higher risk of DM and PCSM. Novel predictive biomarkers are needed to identify men harboring micrometastatic disease to avoid potentially futile local therapies or allow for intensification of systemic therapies. PATIENT SUMMARY: Many men will develop biochemical recurrence of prostate cancer after salvage radiotherapy. Men with biochemical recurrence within 18 mo of salvage radiotherapy constitute a cohort at higher risk of distant metastasis and prostate cancer-specific mortality.

AB - BACKGROUND: Disease progression following salvage radiotherapy (SRT) for prostate cancer (PC) is common, and the time to biochemical recurrence (BCR) is heterogeneous. OBJECTIVE: To describe the temporal distribution and clinical impact of BCR following SRT and model outcomes using patient age and time to BCR from SRT. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multi-institutional study included 547 consecutive men with lymph node-negative PC receiving SRT from 1985 to 2013. The median follow-up after SRT was 8.4 yr. Intervention All men received SRT with three-dimensional or intensity-modulated RT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: BCR was defined as a rise in prostate-specific antigen (PSA) ≥0.2ng/ml above the PSA nadir followed by a sequentially equal or higher value. Additional outcomes included distant metastasis (DM), PC-specific mortality (PCSM), and overall mortality (OM). Cox proportional hazards models, a landmark analysis, and comparison of c-indices were used. Cumulative incidence curves were estimated from a Fine and Gray regression model. RESULTS AND LIMITATIONS: The estimated 10-yr cumulative incidence of BCR was 60%. Of the 274 men experiencing BCR, 149 (54%) had BCR within 18 mo of SRT. BCR ≤18 mo after SRT was associated with a higher risk of DM (hazard ratio [HR] 7.44, 95% confidence interval [CI] 4.91-11.3; p<0.001), PCSM (HR 12.3, 95% CI 5.95-25.2; p<0.001), and OM (HR 2.85, 95% CI 1.94-4.17; p<0.001). We provide a model to estimate the cumulative incidence of DM and PCSM using age and time to BCR. The retrospective nature of our analysis limits our findings. CONCLUSIONS: A strikingly large proportion of men experience early BCR following SRT and are at higher risk of DM and PCSM. Novel predictive biomarkers are needed to identify men harboring micrometastatic disease to avoid potentially futile local therapies or allow for intensification of systemic therapies. PATIENT SUMMARY: Many men will develop biochemical recurrence of prostate cancer after salvage radiotherapy. Men with biochemical recurrence within 18 mo of salvage radiotherapy constitute a cohort at higher risk of distant metastasis and prostate cancer-specific mortality.

KW - Biochemical failure

KW - Postprostatectomy

KW - Salvage radiation therapy

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