10 year outcomes after monitoring, surgery, or

RESEARCH POSTER PRESENTATION TEMPLATE © 2019

www.PosterPresentations.com

Presented by: Taylor Schumacher & Jennifer Carraux

Freddie C. Hamdy, F.R.C.S.(Urol.), F.Med.Sci., Jenny L. Donovan, Ph.D., F.Med.Sci., J. Athene Lane, Ph.D., Malcolm Mason, M.D., F.R.C.R., Chris Metcalfe, Ph.D., Peter Holding, R.G.N., M.Sc., Michael Davis, M.Sc., et al.

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

INTRODUCTION

METHODS

RESULTS RESULTS CONCLUSIONS

REFERENCES

The article follows men age 50-59 between 1999 and 2009

that were newly diagnosed with clinically localized prostate

cancer. They were then separated randomly into 3 different

groups including active surveillance, radiotherapy, and

radical prostatectomy. The purpose was to gauge the

effectiveness of treatments in terms of premature death. The

importance of this study was to evaluate for an incredibly

pressing concern of prostate cancer throughout not only the

United States, but worldwide. There are uncertainties when it

comes to the way prostate cancer is diagnosed and its

correlation to treatment outcomes. This study (a two-part

study initially published in 2014) found low cancer specific

mortality regardless of treatment.2 The study referred to its

initial randomized trial which focused more on methodology

of diagnosis as well as other literature with randomized trials

comparing prostatectomy with active surveillance or

radiotherapy. These ranged from randomized controlled

studies to patient reported outcomes. The active monitoring

group differs from previous studies incorporating “watchful

waiting” such as the Scandinavian Prostate Cancer Group

Study Number 4 and the U.S. Prostate Cancer Intervention

versus Observation Trial (PIVOT).3,4,5 In the current study

patients were assessed for changes in PSA levels and as a

result clinical management could be modified whereas in the

2 latter studies mentioned no intervention was provided.3,4,5

Despite the differences among the trials PIVOT concluded

that there was not a significant difference in cancer-specific

mortality rates between watchful waiting and radical

prostatectomy. However, amongst the Scandinavian trials it

was concluded that radical prostatectomy helped to reduce

cancer-specific mortality, but did not have a difference

between overall survival.3,6 Adding in the perspective of

prostatectomy versus radiotherapy, a meta-analysis

completed found increased overall risk of mortality, both non

cancer-specific and cancer-specific.7 Per a retrospective

study there was an insignificant difference found amongst

prostatectomy and radiotherapy.8

This study was a prospective trial that compared active

monitoring, radical prostatectomy, and external-beam

radiotherapy for the treatment of localized prostate cancer. A

total of 82,429 men 50 to 69 years of age received a PSA

test between 1999 and 2009. Of that 2664 received the

diagnosis of clinically localized prostate cancer, and 1643

agreed to undergo randomization. After randomization 545

men were active monitoring, 545 underwent radiotherapy,

and 553 men underwent surgery. The goal of randomization

was to ensure the groups were made to be as similar in

demographics as possible with respect to age, Gleason

score, mean baseline from the first biopsy and PSA test.

Prostate-cancer mortality at a median of 10-year follow-up

was the primary outcome. The secondary outcome included

the rates of disease progression, metastases, and all deaths.

A total of 14 patients were lost to follow up for secondary

outcomes, but data on deaths were captured for all

participants. Sensitivity analyses excluded men that were

recruited during the feasibility phase or that included deaths

that were judged to be possibly due to prostate cancer. Men

were also excluded based on PSA test results from the initial

randomized control trial.

Figure 1. Randomization, Treatment, and Follow-up.A

total of 88% of the men assigned to active monitoring, 71% of

the men assigned to surgery, and 74% of men assigned to

radiotherapy received the assigned treatment within 9

months after randomization. A total of 14 patients were lost to

follow-up for secondary outcomes, but data on deaths were

captured for all participants.

Table 2. Deaths from Prostate Cancer, According to

Subgroup.

The results found that of the 1643 men included, 14 were lost

to follow up due to outcomes during the follow up period, but

were still included in the study. They found secondary issues

within the study where 291 of the active monitoring group

ended up receiving some sort of radical treatment, which

included surgery and/or radiotherapy. Of the prostatectomy

group, 6 had to receive some sort of radiotherapy 1-year post

surgery. Of the radiotherapy group, 3 had to undergo savage

prostatectomy, and 15 received additional treatment. They

determined that 7-8 of the deaths in the active surveillance

group were prostate cancer specific, 3-5 in the surgery

group, and 4 in the radiotherapy group. Survival specific to

prostate cancer was determined to be around 98.8% in all

groups with an insignificant difference between the groups.

204 out of the total men were found to have disease

progression including metastasis (46 in the surgery, 112 in

the active surveillance, and 46 in the radiotherapy group).

There were minimal complications reported post treatment

although there were 3 deaths determined to be unrelated to

prostate cancer in the radiotherapy group. Numbers needed

to treat were determined to be 27 men for prostatectomy for

1 avoiding metastatic disease and 33 with radiotherapy. If

combined the number lowers to 9 men. The author

concluded that amongst all three treatment groups there was

no significant difference in prostate-cancer related deaths

over a 10-year span post intervention. However, it found that

prostatectomy and radiotherapy were associated with lower

incidences of progressing disease as opposed to the active

monitoring group. The long-term effects of intervention still

need to be evaluated to form a more educated and evidence-

based decision on treatment. One factor not incorporated or

considered in the study was quality of life for which the

author appears to want to follow up on in future studies. The

study was limited in not considering quality of life or the

specific outcomes post-surgical or radiotherapy. With the

smaller sample size and the sample being solely out of the

UK certain factors such as if there are any differences in the

prostate cancer seen in the UK versus anywhere else in the

world was not addressed. The study and the previous

randomized trial can help to try and establish the benefit of

PSA testing in diagnosis of prostate cancer regarding overall

outcomes.

1. Hamdy FC, Donovan JL, Lane, JA et al. 10-Year outcomes after monitoring, surgery, or

radiotherapy for localized prostate cancer. N Engl J Med. 2016; 375:1415-1424. doi:

10.1056/NEJMoa1606220

2. Lane JA, Donovan JL, Davis M, et al. Active monitoring, radical prostatectomy, or

radiotherapy for localised prostate cancer: study design and diagnostic and baseline results

of the ProtecT randomised phase 3 trial [published correction appears in Lancet Oncol.

2014 Oct;15(11):e475]. Lancet Oncol. 2014;15(10):1109–1118. doi:10.1016/S1470-

2045(14)70361-4

3. Holmberg L, Bill-Axelson A, Helgesen F, et al. A randomized trial comparing radical

prostatectomy with watchful waiting in early prostate cancer. N Engl J Med 2002;347:781-

789

4. Wilt TJ, Brawer MK, Barry MJ, et al. The Prostate cancer Intervention Versus

Observation Trial: VA/NCI/AHRQ Cooperative Studies Program 407 (PIVOT): design and

baseline results of a randomized controlled trial comparing radical prostatectomy to watchful

waiting for men with clinically localized prostate cancer. Contemp Clin Trials 2009;30:81-87

5. Bill -Axelson A, Holmberg L, Garmo H, et al. Radical prostatectomy or watchful waiting in

early prostate cancer. N Engl J Med. 2014;370(10):932–942. doi:10.1056/NEJMoa131159

6. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for

localized prostate cancer. N Engl J Med 2012;367:203-213

7. Wallis CJD, Saskin R, Choo R, et al. Surgery Versus Radiotherapy for Clinically-localized

Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol. 2016;70(1):21–30.

doi:10.1016/j.eururo.2015.11.010

8. Andic F, Izol V, Gokcay S, et al. Definitive external-beam radiotherapy versus radical

prostatectomy in clinically localized high-risk prostate cancer: a retrospective study. BMC

Urol. 2019;19(1):3. Published 2019 Jan 5. doi:10.1186/s12894-018-0432-6

Table 1. Prostate-Cancer Mortality, Incidence of Clinical

Progression and Metastatic Disease, and All-Cause Mortality,

According to Randomized Treatment Group.

Figure 2. Kaplan–Meier Estimates of Prostate-Cancer–Specific

Survival and Freedom from Disease Progression, According to

Treatment Group Panel A shows the rate of prostate-cancer–

specific survival. Prostate-cancer–specific deaths were those

that were definitely or probably due to prostate cancer or its

treatment, as determined by an independent cause-of-death

evaluation committee whose members were unaware of the

treatment assignments. Panel B shows the rate of freedom from

disease progression. Clinical progression of prostate cancer

included metastasis and death due to prostate cancer or its

treatment.