Long term survival outcomes of ejaculate donors for cancer research: implications for patient management*

D Ashrafi, P Baade, J Yaxley, S Williams, RA Gardiner

The Universityof QueenslandCentre for ClinicalResearch

Royal Brisbane &Women’s Hospital Department of Urology

The Cancer CouncilQueensland

Peter MacCallum Cancer Centre

*Accepted for publication in European Focus

Background

Prostate Cancer Intervention vs Observation (PIVOT) trial Wilt et al, 2012;

No difference in overall survival ratesNo difference in prostate cancer specific survivalAggressive therapy did not improve survival

Which patients will survive long enough to benefit from interventions with curative intent?

Life expectancy of at least 10 years justifies investigation and treatment WaBasch et al, 2012; Heidenreich et al, 2013

Doctors poor at predicting life expectancy Waltz et al, 2007; Wilt et al, 2012; Bill-Axelson et al, 2014; Daskivich et al, 2014

No prediction tool used in clinical practice Kent et al, 2014;

Survival estimation

Erectile dysfunction

Onset of ED is an indicator of cardiovascular-related mortality Chew et al, 2011; Banks et al, 2013

Median time of death from onset is 10 years Chew et al, 2011; Banks et al, 2013

Accuracy of completed questionnaires for ED less than perfect due to comprehension Oztürk et al, 2011 & inaccurate recall Cooperberg et al, 2003

Hypothesis

Volunteers who provided ejaculate specimens have a high survival rate at 10 and 15 years relative to the general population

AimEvaluate overall and relative survival for ejaculate donors between 1992 and 2003

A simple indicator of life expectancy in early prostate cancer?

Ethics approvalUniversity of Queensland HREC (Project no. 2006000262)Royal Brisbane Women’s Hospital HREC (94/29; 1995/088B)

Patient cohortJanuary 1992 to May 2003RBWH Urology Unit and Private Consulting roomsInvestigation of abnormal PSA or abnormal digital rectal

examVolunteer ejaculate specimen for prostate cancer researchVolunteers booked for diagnostic TRUS biopsyEjaculate specimens collected prior to or one month after

biopsy

Methods

Patient outcomesDeadAlive (as of 31st December 2013)

Survival from time of ejaculate donationSurvival status obtained from various sourcesDeaths verified by National Death Index

Subgroups:Biopsy statusPSA levelsAge at time of ejaculate donation

Data Measures

Primary outcome All-cause survivalKaplan-Meier generated for subgroups

Comparative groupsQueensland total population dataQueensland Cancer registry data

Relative survivalComparison of survival outcomes between our cohort and

comparative groupsMatched by age- and sex-matched population

Statistical Analysis

Cohort DataTotal

CohortNo

CancerOther Cancer

PCa

Age20-49 25 18 1 7

50-65 151 61 13 77

>65 113 32 12 69

Other 1 1

PSA

<4 80 40 11 29

4-10 95 38 6 51

>10 87 19 8 60

? 28 14 1 13

Total 290 111 26 153

Cohort DataTotal

CohortNo

CancerOther Cancer

PCa

Age20-49 25 18 1 7

50-65 151 61 13 77

>65 113 32 12 69

Other 1 1

PSA

<4 80 40 11 29

4-10 95 38 6 51

>10 87 19 8 60

? 28 14 1 13

Total 290 111 26 153

Cohort DataTotal

CohortNo

CancerOther Cancer

PCa

Age20-49 25 18 1 7

50-65 151 61 13 77

>65 113 32 12 69

Other 1 1

PSA

<4 80 40 11 29

4-10 95 38 6 51

>10 87 19 8 60

? 28 14 1 13

Total 290 111 26 153

Cohort DataTotal

CohortNo

CancerOther Cancer

PCa

Age20-49 25 18 1 7

50-65 151 61 13 77

>65 113 32 12 69

Other 1 1

PSA

<4 80 40 11 29

4-10 95 38 6 51

>10 87 19 8 60

? 28 14 1 13

Total 290 111 26 153

Prostate cancer28%

Other cancers (non-prostate)26%

Cardiovascular diease15%

Other causes19%

Unknown12%

DeathDeath Alive

n 103 187

Median follow-up 10.7 16.6

Kaplan-Meier all-cause survival estimates0.

00.

20.

40.

60.

81.

0S

urvi

val p

rop

ortio

n

0 5 10 15 20Years after ejaculate

No prostate cancer (n=137) Prostate cancer (n=153)

Subgroup Survival Probability

Relative survival 5-20 years following donation

Follow-up Total Cohort No Cancer Other Cancer PCa5 yr 102% 104.8% 94.9% 101.1%

10 yr 103.1% 110.1% 85% 100.6%15 yr 101.7% 119.4% 70.9% 91.7%20 yr 112.8% 139.9% N/A 95.6%

N 290 111 26 153

Compare survival data with matched populationUsed by ABS and Cancer registriesQueensland life expectancy tables

Relative survival 5-20 years following donation

Follow-up Total Cohort No Cancer Other Cancer PCa5 yr 102% 104.8% 94.9% 101.1%

10 yr 103.1% 110.1% 85% 100.6%15 yr 101.7% 119.4% 70.9% 91.7%20 yr 112.8% 139.9% N/A 95.6%

N 290 111 26 153

Compare survival data with matched populationUsed by ABS and Cancer registriesQueensland life expectancy tables

Relative survival 5-20 years following donation

Follow-up Total Cohort No Cancer Other Cancer PCa5 yr 102% 104.8% 94.9% 101.1% (95-105)

10 yr 103.1% 110.1% 85% 100.6% (91-108)15 yr 101.7% 119.4% 70.9% 91.7% (75-100)20 yr 112.8% 139.9% N/A 95.6% (68-107)

N 290 111 26 153

Compare survival data with matched populationUsed by ABS and Cancer registriesQueensland life expectancy tables

Ages at ejaculation (yrs) Overall survival (QLD population data)

Prostate cancer specific survival (our data)

Relative survival

20-49 years n = 25 100% 100% 103.0%

50-64 years n = 151 88.3% 92.0% 100.2%

>65 years n = 113 65.2% 86.2% 100.2%

All ages combined 78.4% 90.1% 100.6%

Relative survival at 10 years for donors diagnosed with PCa

Ages at ejaculation (yrs) Overall survival (QLD population data)

Prostate cancer specific survival (our data)

Relative survival

20-49 years n = 25 100% 100% 103.0% (81.5%*)

50-64 years n = 151 88.3% 92.0% 100.2% (82.7%*)

>65 years n = 113 65.2% 86.2% 100.2% (65.2%*)

All ages combined 78.4% 90.1% 100.6%

Relative survival at 10 years for donors diagnosed with PCa

*Reference: Queensland Cancer Registry reference for years 1992-2003

No cancer > Queensland population

Prostate cancer = Queensland population

Prostate cancer > Queensland prostate cancer population

Summary

Volunteers who provided ejaculate specimens have a high survival rate at 10 and 15 years relative to the general population

Hypothesis

Conclusions

Ability to provide an ejaculate specimen predicts a high likelihood of survival for men suspected of prostate cancer

Potential for life expectancy tables to indicate survival for ejaculate donors with prostate cancer

Identify patients that would benefit from treatment with curative intent

Questions?

References1. Baade PD, Gardiner RA, Ferguson M et al. Factors associated with diagnostic and treatment intervals for prostate cancer in Queensland, Australia: a large cohort study. Cancer Causes & Control, 2012; 23:625-34 2. Baade PD, Youlden DR, Cramb SM et al. Epidemiology of prostate cancer in the Asia-Pacific region. Prostate Int, 2013; 1(2):47-58 3. Heidenreich A, Bastian PJ, Bellmunt J et al; European Association of Urology. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014; 65(1):124-374. Basch E, Oliver TK, Vickers A et al. Screening for prostate cancer with prostate-specific antigen testing: American Society of Clinical Oncology Provisional Clinical Opinion. J Clin Oncol. 2012; 30(24):3020-5.5. Walz J, Gallina A, Saad F et al. A nomogram predicting 10-year life expectancy in candidates for radical prostatectomy or radiotherapy for prostate cancer. J Clin Oncol. 2007; 25(24):3576-81.6. Wilt TJ, Brawer MK, Jones KM et al; Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012; 367(3):203-13.7. Bill-Axelson A, Holmberg L, Garmo H et al. Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer. N Engl J Med 2014; 370:932-9428. Beyer DC, McKeough T, Thomas T. Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2005; 61(5):1299-305.9. Daskivich TJ, Lai J, Dick AW et al; Urologic Diseases in America Project. Variation in treatment associated with life expectancy in a population-based cohort of men with early-stage prostate cancer. Cancer. 2014; 120(23):3642-5010. Singh R, O'Brien TS. Comorbidity assessment in localized prostate cancer: a review of currently available techniques. Eur Urol. 2004; 46(1):28-4111. Kent M, Vickers AJ. A systematic literature review of life expectancy prediction tools for localized prostate cancer. J Urol, 2014; JURO 1201612. Banks E, Joshy G, Abhayaratna WP et al. Erectile dysfunction severity as a risk marker for cardiovascular disease hospitalisation and all-cause mortality: a prospective cohort study. PLOS Med. 2013;10(1):e1001372. doi: 10.1371/journal.pmed.1001372.13. Chew KK, Gibson N, Sanfilippo F et al. Cardiovascular mortality in men with erectile dysfunction: increased risk but not inevitable. J Sex Med. 2011; 8(6):1761-7114. Oztürk Mİ, Koca O, Keleş MO et al. Question for a questionnaire: the International Index of Erectile Function. Int J Impot Res. 2011; 23(1):24-6.15. Cooperberg MR, Koppie TM, Lubeck DP et al; CaPSURE. How potent is potent? Evaluation of sexual function and bother in men who report potency after treatment for prostate cancer: data from CaPSURE. Urology. 2003; 61(1):190-6.16. Schemper M, Smith TL: A note on quantifying follow-up in studies of failure time. Control Clin Trials 1996, 17(4):343-34617. Ederer F, Axtell LM, Cutler SJ (1961) The relative survival rate: a statistical methodology. Natl Cancer Inst Monogr 6: 101– 12118. Redaniel MT, Martin RM, Gillat D et al. Time from diagnosis to surgery and prostate cancer survival: a retrospective cohort study BMC Cancer 2013, 13:55919. Royston P, Lambert PC. Flexible Parametric Survival Analysis Using Stata: Beyond the Cox Model. College Station, Texas: Stata Press; 2011.20. Royston P. A smooth covariate rank transformation for use in regression models with a sigmoid dose-response function. The Stata Journal. 2014; 14(2): 329-341 21. SEER database http://seer.cancer.gov/statfacts/html/prost.html 22. Holden CA, McLachlan RI, Pitts M et al. Men in Australia Telephone Survey (MATeS): a national survey of the reproductive health and concerns of middle-aged and older Australian men. Lancet. 2005; 366(9481):218-2423. Yu, XQ, Luo Q, Smith DP et al. Geographic variation in prostate cancer survival in New South Wales. Medical Journal of Australia 2014;200(10):586-9024. Hall SE, Holman CD, Wisniewski ZS et al. Prostate cancer: socio-economic, geographical and private-health insurance effects on care and survival. BJU Int. 2005 Jan;95(1):51-8.25. Australian Institute of Health and Welfare. Cancer survival and prevalence in Australia: Period estimates from 1982 to 2010. Asia-Pacific Journal of Clinical Oncology. 2013; 9(1): 29-3926. Barry MJ, Andriole GL, Culkin DJ et al. Ascertaining cause of death among men in the prostate cancer intervention versus observation trial. Clin Trials. 2013;10(6):907-14.27. Pagidipati NJ, Gaziano TA. Estimating deaths from cardiovascular disease: a review of global methodologies of mortality measurement. Circulation. 2013; 127(6):749-56.

10 year survival for age and PSA at ejaculationTotal

Cohort10y

survivalNo

Cancer10y

survivalOther Cancer

10y survival

PCa 10y survival

Age20-49 25 100% 18 100% 1 100% 7 100%

50-65 151 91.4% 61 96.7% 13 84.6% 77 88.3%

>65 113 69% 32 87.5% 12 41.7% 69 65.2%

Other 1 1

PSA

<4 80 88.8% 40 92.5% 11 81.8% 29 86.2%

4-10 95 87.4% 38 92.1% 6 66.7% 51 86.3%

>10 87 70.1% 19 100% 8 50% 60 63.3%

? 28 96.4% 14 100% 1 100% 13 100%

Total 290 83.5% 111 94.6% 26 65.4% 153 78.3%

Median follow-up

16.9 17.9 16.1Median FU = 15.6 yr: 10.4 yr those who died: 16.6 yr those alive - range 10.9-20.5 yr

Ages at ejaculation (yrs) General population survival Prostate cancer specific survival

Relative survival

20-49 years n = 25 100% 100% 103.0%

50-64 years n = 151 88.3% 92.0% 100.2%

>65 years n = 113 65.2% 86.2% 100.2%

All ages combined 78.4% 90.1% 100.6%

Survival at 10 years for donors diagnosed with PCa

Life Expectancy Table Queensland Males

Age 1995-97 2002--04 2010-12

61 19.3 21.0 22.2

63 17.8 19.4 20.6

65 16.3 17.8 18.9

67 14.9 16.3 17.4

69 13.6 14.8 15.8

71 12.3 13.4 14.3

73 11.1 12.1 12.9

75 10.0 10.8 11.6

76 9.4 10.2 10.9

80 7.5 8.0 8.5