Patient-Reported Outcomes 12 Years after Localized Prostate Cancer Treatment

Donovan, Jenny; Hamdy, Freddie C.; Lane, J. Athene; Metcalfe, Chris; Walsh, Eleanor; Davis, Michael J.; Steuart-Feilding, Thomas; Blazeby, Jane; Avery, Kerry; Martin, Richard M; Bollina, Prasad; Doble, Andrew; Doherty, Alan; Gillatt, David; Gnanapragasam, Vincent; Hughes, Owen; Kockelbergh, Roger; Kynaston, Howard; Paul, Alan; Páez, Edgar; Powell, Philip A.; Rosario, Derek J.; Rowe, Edward; Mason, Malcolm David; Catto, James W.F.; Peters, Tim; Wade, Julia; Turner, Emma; Williams, Naomi; Oxley, Jon; Staffurth, John; Bryant, Richard J.; Neal, David E.

doi:10.1056/evidoa2300018

Cited by 37 publications

(27 citation statements)

References 29 publications

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“…The ProtecT randomized trial compared open radical prostatectomy, EBRT with ADT, and active monitoring for localized PC. 9 Despite reporting similar patterns of functional outcomes compared with findings in this study, some adverse outcome rates were higher in ProtecT. Specifically, 18% of patients with low-risk PC in ProtecT after both radical prostatectomy and radiation therapy had erections sufficient for intercourse at 10 years compared with 31% and 26% with favorable-prognosis PC in findings in this study after radical prostatectomy and EBRT, respectively.…”

Section: Discussionsupporting

confidence: 41%

“…Evidence is lacking regarding the relative associations of each treatment with functional outcomes, according to whether the patient has a favorable or unfavorable prognosis. [3][4][5][6][7][8][9] Therefore, the population-based Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study enrolled men diagnosed with localized PC in 2011-2012 and followed them up for approximately 10 years to compare patientreported outcomes according to treatment received at baseline.…”

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confidence: 99%

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Functional Outcomes After Localized Prostate Cancer Treatment

Al Hussein Al Awamlh,

Wallis,

Penson

et al. 2024

JAMA

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ImportanceAdverse outcomes associated with treatments for localized prostate cancer remain unclear.ObjectiveTo compare rates of adverse functional outcomes between specific treatments for localized prostate cancer.Design, Setting, and ParticipantsAn observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level &lt;20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022.ExposuresRadical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease.Main Outcomes and MeasuresOutcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function.ResultsA total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, −12.1 [95% CI, −16.2 to −8.0]), but not worse sexual function (adjusted mean difference, −7.2 [95% CI, −12.3 to −2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, −26.6 [95% CI, −35.0 to −18.2]), but not worse sexual function (adjusted mean difference, −1.4 [95% CI, −11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, −4.9 [95% CI, −9.2 to −0.7]) and hormone (adjusted mean difference, −4.9 [95% CI, −9.5 to −0.3]) function compared with radical prostatectomy.Conclusions and RelevanceAmong patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.

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Section: Discussionsupporting

confidence: 41%

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confidence: 99%

Functional Outcomes After Localized Prostate Cancer Treatment

Al Hussein Al Awamlh,

Wallis,

Penson

et al. 2024

JAMA

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“…Early radical treatments therefore can result in more harm than good. Clinicians need to avoid over-treatment by ensuring that men with newly diagnosed prostate cancer consider critical 'trade-offs' between shortand long-term effects of treatments on urinary, bowel and sexual function, 13 as well as the risks of progression.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] Patient-reported outcomes, critical to assessing the full trade-offs between treatment benefits and harms are described in a separatecompanion article. 13…”

Section: Introductionmentioning

confidence: 99%

Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer

et al. 2023

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“…Localized PCa may be treated with curative intent by radical surgery, or RT with concomitant androgen-deprivation therapy (ADT), with equivalent rates of post-treatment disease progression, but differences in side effect profiles, at 15-years clinical follow-up 1,2 . In the clinical oncology setting, it is recognized that at long-term follow-up a group of patients will experience disease progression following RT 3 .…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those withde novometastatic disease

Charlton,

O’Reilly,

Philippou

et al. 2023

Preprint

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Purpose: It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies from cohorts with post-radiotherapy (RT) long-term clinical follow-up has been limited. Utilizing parallel sequencing modalities, we performed a proof-of-principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with i) stable PCa post-primary or salvage RT (sPCa), ii) progressing PCa post-RT (pPCa), and iii) de novo metastatic PCa (mPCa). Experimental Design: A cohort of 19 patients with diagnostic prostate biopsies (n=6 sPCa, n=5 pPCa, n=8 mPCa) and mean 4 years 10 months follow-up (diagnosed 2009-2016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3"RNA sequencing (3"RNAseq) (n=19), nanoString analysis (n=12) and Illumina 850k methylation (n=8) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes (DEGs) and methylated genomic regions (MGRs). Results: 18 of 19 samples provided useable 3"RNAseq data. Principal Component Analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ~600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression-free survival post-RT (p<0.0001) in an external cohort. Conclusions: 3"RNAseq, nanoString and 850K-methylation analyses are each achievable from historical FFPE diagnostic pre-treatment prostate biopsies, unlocking the potential to utilize large cohorts of historic clinical samples. Profiling similarities between individuals with pPCa and mPCa suggests biological similarities and historical radiological staging limitations, which warrant further investigation.

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Patient-Reported Outcomes 12 Years after Localized Prostate Cancer Treatment

Cited by 37 publications

References 29 publications

Functional Outcomes After Localized Prostate Cancer Treatment

Functional Outcomes After Localized Prostate Cancer Treatment

Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer

Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those withde novometastatic disease

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