CUA 2017: What’s New in Patient-Reported Outcomes Following Treatment for Localized Prostate Cancer?

Toronto, Ontario ( Dr. David Penson, the Paul V. Hamilton, M.D. and Virginia E. Howd Chair in Urologic Oncology and Professor of Urologic Surgery and Medicine at Vanderbilt University Medical Center, gave an excellent talk highlighting the status of patient-reported outcomes (PROs) following treatment for localized prostate cancer (PCa). 

From a historic perspective, prior studies have assessed patients treated in the 1990’s for localized prostate cancer with open radical prostatectomy (RRP) or external beam radiation therapy (EBRT). In those analyses of 5-year PROs, surgery had slightly higher urinary incontinence rates (13%) than EBRT (4%), while EBRT had higher bowel symptoms (31% vs. 16%), but both had similar erectile dysfunction rates (erections insufficient for intercourse). More importantly, though, these studies assessed treatment in a different era. 

Since that time, there have been improvements or changes in surgical technique (robotic surgery [RALP]), radiation therapy (intensity-modulated and image-guided radiotherapy), local therapies (HIFU, proton beam, etc) and introduction of active surveillance (AS). Unfortunately, PRO evaluations have not kept up with these changes. Most subsequent studies have been single-institution experiences and series, which inherently present a biased picture towards better outcomes – usually as they are high volume centers with increased experience and better institutional protocols. Well-designed, large, multicenter PRO studies are needed.

In this talk, he focused on three large studies published in the last 6 months. While they aren’t perfect, they represent a start of the discussion. The first is the PRO assessment of the well publicized ProtecT study.1 He noted the following caveats as the results are reviewed: all the XRT patients received 3-6 months neoadjuvant ADT, 56% of the active monitoring arm received definitive therapy by the end of the study, and only about 70% of each arm actually received the treatment they were randomized to. As such, the results are not a pure assessment of each treatment modality. The next study was by Chen et al,2 and utilized the North Carolina Prostate Cancer Comparative Effectiveness & Survivorship Study (NC-ProCESS) data. He noted that, unlike the other two studies which used the EPIC survey, they used the PROMIS survey to assess PRO – unfortunately, individual item data was not presented, making it hard to incorporate and compare. They assessed patients for up to 2 years after treatment. However, they did use propensity score analysis and multiple imputation to account for missing data. Lastly, he reviewed the CEASAR study (Comparative Effectiveness Analysis of Surgery and Radiation in localized Prostate Cancer),3 which he was a part of. This was an augmented population-based observational study – utilized a retrospective cohort using 5 SEER databases and CaPSURE datasets, but also recruited 3269 patients prospectively prior to treatment. All patients recruited completed the EPIC survey at baseline and at 6, 12 and 36 months They also utilized propensity score analysis and multiple imputation for missing data. A review of the last two papers can be found on Nature Reviews Urology.4

He then went through each of four domains individually: sexual function outcome, urinary continence, urinary irritative symptoms, and bowel function outcomes.

Sexual Function Outcomes
In the ProtecT trial, RP patients do quite poorly (35% ED at baseline, 85% at one year, but still 80% ED at 5 years), EBRT patients do slightly better (32% ED at baseline, 62% at 1 year, sight rise to 73% by 5 years), while active monitoring does worse than expected (33% ED baseline, 65% by 5 years) – however, active monitoring in this study included many patients who received intervention. In the NC-ProCESS trial, since individual scores were not rated, they broke down the results into normal, intermediate and poor. In the patients with normal erectile function at baseline, RP caused significant ED (only 9% with normal erectile function at 2 years, 57% with poor function), while brachytherapy and EBRT caused some insult (27-36% with normal function, 27-34% with poor function). AS patients did the best, but still had some loss of function (45% normal at 2 years, 25% poor function). In the CEASAR study, the RP and EBRT trends were similar to the other studies – RP patients took the biggest hit (39% ED at baseline, 80% at 1 year, 70% at 3 years), EBRT (56% at baseline, 71% at 1 year, 71% at 3 years). AS patients were more stable (41% at baseline, 45% at 1 year, 51% at 3 years).

Some important take-home points:
1. Surgery is not as good as we tell our patients it will be based on single-institution series!

2. Nerve-sparing doesn’t help as much as we think – in a separate analysis, nerve-sparing RP vs. non-nerve sparing RP only provided a 10% increased likelihood of good erectile function at 3 years (44% vs. 34%). EBRT with or without ADT did better (61-65%), and AS was the best (73%)

3. Nerve-sparing provided the most benefit in men between age 60-70. Older men did poorly regardless, and younger men did well regardless.

4. Localized therapy, despite improvements in technique, have not had much improved in sexual function outcomes

Age, baseline sexual function and time from treatment were the strongest predictors of potency – more than race, sexual partners, nerve sparing, use of erectile aids, etc.

Urinary Incontinence Outcomes
Similar to sexual function outcomes, the results for radical prostatectomy are poor across all the studies. In the ProtecT trial, RP patients do quite poorly (70% continence at baseline, 29% at one year, but still 31% continence at 5 years), EBRT and AS patients do slightly better (69-72% continence at baseline, 52-53% at 5 years). NC-ProCESS results were similar – 16% of men undergoing RP who had normal continence at baseline had poor continence at 2 years; compared to 7-9% for AS and EBRT and brachytherapy. In the CEASAR study, patients undergoing RP had a 10% higher rate of incontinence at 3 years compared to EBRT or AS. 

Take Home Points:
RP is still associated with significantly more urinary incontinence – no significant improvement with modern techniques

Urinary Irritative Symptoms
In this area, RP did slightly better than EBRT and even AS. However, the numbers were not as impressive. 24% of brachytherapy patients in NC-ProCESS with normal baseline function had poor function at 2 years, compared to 8% in RP, 13% in AS, and 15% in EBRT. In CEASAR, EBRT and RP were similar early after intervention, but RP did slightly better after 18 months. 

Take Home Points:
1. Modern EBRT techniques appear to be better than older techniques

2. Brachytherapy is likely associated with worse irritative symptoms

Bowel Function Outcomes
Ultimately, for bowel function, surgery and active surveillance were similar and had minimal effect on bowel function. Despite advances in radiation technique, a small but significant (5-10%) of radiation patients have bowel symptoms up to 3-5 years after treatment.

Summary and Moving Forward
1. What mattered most? For all 4 outcomes, baseline status was the most important predictor of outcomes. Therefore, patient selection matters.

2. There has not been much improvement in PROs in 20 years, despite advances in technology and technique

3. Large single-institution series paint an unrealistic picture for patients entering therapy. For surgeons who do not do keep track of their own statistics, they should cite large community based series instead. Sobering facts:
    a. Potency rates are 10-30% (not 60-97% as in prior single-institution series)
    b. Incontinence rates are 15-20% (not 10-15% as in prior single-institution series)

4. Outcomes are probably worse in these larger series for multiple reasons, but patient selection likely plays an important role.
    a. In the CEASAR data, 56% of patients with poor erectile function at baseline had bilateral nerves sparing!
5. Centralizing prostate cancer care may help address some of these issues
    a. Currently, median number of RP’s done per year by surgeon is ~8

6. Be really honest with patients and ourselves about surgical and radiation outcomes

Presented By: Dave F. Penson, MD, MPH, Vanderbilt University, Nashville, Tennessee

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto   Twitter: @tchandra_uromd at the  72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada

1. Donovan JL, Hamdy FC, Lane JA, Mason M, Metcalfe C, Walsh E, Blazeby JM, Peters TJ, Holding P, Bonnington S, Lennon T, Bradshaw L, Cooper D, Herbert P, Howson J, Jones A, Lyons N, Salter E, Thompson P, Tidball S, Blaikie J, Gray C, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Davis M, Turner EL, Martin RM, Neal DE; ProtecT Study Group. Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. 2016 Oct 13;375(15):1425-1437. doi: 10.1056/NEJMoa1606221. Epub 2016 Sep 14.

2. Chen RC, Basak R, Meyer AM, Kuo TM, Carpenter WR, Agans RP, Broughman JR, Reeve BB, Nielsen ME, Usinger DS, Spearman KC, Walden S, Kaleel D, Anderson M, Stürmer T, Godley PA. Association Between Choice of Radical Prostatectomy, External Beam Radiotherapy, Brachytherapy, or Active Surveillance and Patient-Reported Quality of Life Among Men With Localized Prostate Cancer.JAMA. 2017 Mar 21;317(11):1141-1150. doi: 10.1001/jama.2017.1652.

3. Barocas DA, Alvarez J, Resnick MJ, Koyama T, Hoffman KE, Tyson MD, Conwill R, McCollum D, Cooperberg MR, Goodman M, Greenfield S, Hamilton AS, Hashibe M, Kaplan SH, Paddock LE, Stroup AM, Wu XC, Penson DF. Association Between Radiation Therapy, Surgery, or Observation for Localized Prostate Cancer and Patient-Reported Outcomes After 3 Years. JAMA. 2017 Mar 21;317(11):1126-1140. doi: 10.1001/jama.2017.1704. Erratum in: JAMA. 2017 May 23;317(20):2134.

4. Chandrasekar T, Tilki D. Prostate cancer: Comparing quality of life outcomes after prostate cancer treatment. Nat Rev Urol. 2017 Jun 13. doi: 10.1038/nrurol.2017.81. [Epub ahead of print] No abstract available.

5. Wallis CJD, Glaser A, Hu JC, Huland H, Lawrentschuk N, Moon D, Murphy DG, Nguyen PL, Resnick MJ, Nam RK. Survival and Complications Following Surgery and Radiation for Localized Prostate Cancer: An International Collaborative Review. Eur Urol. 2017 Jun 10. pii: S0302-2838(17)30495-5. doi: 10.1016/j.eururo.2017.05.055. [Epub ahead of print] Review.