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Article of the Month: SRP for recurrent Prostate Cancer – Verification of EAU guideline criteria

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Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Salvage Radical Prostatectomy for recurrent Prostate Cancer: Verification of EAU guideline criteria

Philipp Mandel*†, Thomas Steuber*†, Sascha Ahyai†, Maximilian Kriegmair‡, Jonas Schiffmann*, Katharina Boehm*, Hans Heinzer*, Uwe Michl*, Thorsten Schlomm*†, Alexander Haese*, Hartwig Huland*, Markus Graefen* and Derya Tilki*†

 

*Martini-Clinic Prostate Cancer Center, †Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg , and ‡Department of Urology, University Hospital Mannheim, Mannheim, Germany

 

Note: Figure 3 should be swapped with Figure 4. The legends for both figures stay the same and the referencing in the text is correct.

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OBJECTIVE

To analyse oncological and functional outcomes of salvage radical prostatectomy (SRP) in patients with recurrent prostate cancer and to compare outcomes of patients within and outside the European Association of Urology (EAU) guideline criteria (organ-confined prostate cancer ≤T2b, Gleason score ≤7 and preoperative PSA level <10 ng/mL) for SRP.

PATIENTS AND METHODS

In all, 55 patients who underwent SRP from January 2007 to December 2012 were retrospectively analysed. Kaplan–Meier curves assessed time to biochemical recurrence (BCR), metastasis-free survival (MFS) and cancer-specific survival. Cox regressions addressed factors influencing BCR and MFS. BCR was defined as a PSA level of >0.2 ng/mL and rising, continence as the use of 0–1 safety pad/day, and potency as a five-item version of the International Index of Erectile Function score of ≥18.

RESULTS

The median follow-up was 36 months. After SRP, 42.0% of the patients experienced BCR, 15.9% developed metastasis, and 5.5% died from prostate cancer. Patients fulfilling the EAU guideline criteria were less likely to have positive lymph nodes (LNs) and had significantly better BCR-free survival (5-year BCR-free survival 73.9% vs 11.6%; P = 0.001). In multivariate analysis, low-dose-rate brachytherapy as primary treatment (P = 0.03) and presence of positive LNs at SRP (P = 0.02) were significantly associated with worse BCR-free survival. The presence of positive LNs or Gleason score >7 at SRP were independently associated with metastasis. The urinary continence rate at 1 year after SRP was 74%. Seven patients (12.7%) had complications ≥III (Clavien grade).

CONCLUSION

SRP is a safe procedure providing good cancer control and reasonable urinary continence. Oncological outcomes are significantly better in patients who met the EAU guideline recommendations.

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Editorial: SRP – a few good men

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The current management of recurrent disease after definitive treatment of a localized prostate cancer with radiation therapy (RT) or cryotherapy remains debatable. A substantial portion of patients treated with RT (20–50%) will experience biochemical recurrence. Androgen deprivation therapy has been the mainstay of therapy for this patient population, especially if there was concern about metastatic spread. As the initial experience with salvage radical prostatectomy (SRP) was highly morbid with poor functional outcomes, this did not gain strong acceptance as a recommended treatment method; however, with improved functional outcomes and fewer complications reported in recent series, SRP has once again become a viable alternative in select cases.

The rarity of the procedure makes it difficult to generate large-volume prospective studies on SRP, requiring us to depend on retrospective series. Chade et al. [1] published the largest series of patients undergoing SRP through a multicentre collaborative effort, and were able to identify 404 patients treated between 1985 and 2009; other large series were limited to 50–200 patients. In their systematic review of studies published between 1980 and 2011, Chade et al. [2] reported 5- and 10-year biochemical recurrence-free survival rates of 47–82% and 28–53%, respectively. This broad range of outcomes hints at the variable response of patients to SRP. Identifying the subset of patients who are most likely to benefit from SRP will therefore help tailor therapies for patients who have failed RT, cryotherapy or high-intensity focused ultrasonography.

As described by Mandel et al. [3], there are three sets of guidelines currently addressing patient selection for SRP. The NICE guidelines are the least specific, essentially mentioning SRP as an option for management without specifying specific criteria [4]. The European Association of Urology (EAU) and National Comprehensive Cancer Network guidelines are more specific, and help narrow the patient population to men with clinically localized recurrence (cT1–2), life expectancy of at least 10 years and a preoperative PSA level <10 ng/mL[5, 6]. The EAU guidelines are even more restrictive, limiting selection to men with Gleason ≤7 on prostate biopsy, although they do not specify whether that is before or after RT [5].

In their retrospective analysis of 55 patients treated with SRP between 2007 and 2012, Mandel et al. [3] compare the oncological outcomes of patients treated according to the EAU criteria (n = 32) and those treated without meeting the EAU criteria (n = 23). The 5-year biochemical recurrence-free survival rate was 48.7%, consistent with previous studies, as was the 5-year cancer-specific survival rate of 89%. Importantly, however, after stratification based on EAU criteria, the 5-year biochemical recurrence-free survival rates were drastically different: 73.9% in patients who met the EAU criteria and 11.6% in patients who did not. Patients who did not meet the EAU criteria were more likely to have Gleason score ≥8 (P = 0.08) tumours and pN1 (nodal metastatic) disease at the time of SRP (P = 0.04), which shows the ability of these criteria to select patients with localized disease recurrence. They also established that overall functional outcomes were acceptable after this procedure, with a postoperative urinary continence rate of 74%; none of the patients recovered potency, however, which is not surprising considering the high rate of preoperative erectile dysfunction and the non-nerve-sparing nature of the procedure [3].

In terms of complications, 12.7% of the patients had Clavien ≥ III complications requiring additional intervention. When complications do occur, they can be severe: three of the patients (5.5%) developed rectovesical fistulae and failed conservative management, progressing to fistula repair with omental flap, and two of the patients required permanent urinary diversion. There was no specification, however, regarding which subset of patients experienced these complications. The complication rate was acceptable, and consistent with recent reports of decreased complication rates with SRP [3].

While the study has its limitations as a retrospective review of a relatively small cohort, it is the first to analyse outcomes based on published guidelines criteria, and thereby helps to validate the subset of patients that will benefit from surgical intervention. Based on their findings, appropriately selected patients, those with evidence of truly localized recurrent disease after RT or high-intensity focused ultrasonography, can have significant oncological benefit with acceptable functional outcomes and without significant morbidity. The goal is not to perform SRP indiscriminately, rather to wait for a few good men.

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Thenappan Chandrasekar , and Christopher P. Evans
Department of Urology, University of California, Sacramento, CA, USA

 

References

 

1 Chade DC, Shariat SF, Cronin AM et al. Salvage radical prostatectomy for radiation-recurrent prostate cancer: a multi-institutional collaboration. Eur Urol 2011; 60: 205–10

 

2 Chade DC, Eastham J, Graefen M et al. Cancer control and functional outcomes of salvage radical prostatectomy for radiation-recurrent prostate cancer: a systematic review of the literature. Eur Urol 2012; 61: 961–71

 

3 MandelP, Steuber T, Ahyai S et al. Salvage radical prostatectomy for recurrent prostate cancer: verification of European Association of Urology guideline criteria. BJU Int 2015; 117: 55–61

 

4 Prostate cancer: diagnosis and treatment. NICE clinical guideline 175: Hearing before the National Institute for Health and Care Excellence (January 2014).

 

5 Heidenreich A, Bastian PJ, Bellmunt J et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 2014; 65: 467–79

 

6 Mohler JL, Kantoff PW, Armstrong AJ et al. Prostate cancer, version 2.2014. JNCCN 2014; 12: 686–718.

 

 

Article of the week: Men under 50 should not be discouraged from radical prostatectomy

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by prominent members of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Andreas Becker discussing his paper.

If you only have time to read one article this week, it should be this one.

Functional and oncological outcomes of patients aged <50 years treated with radical prostatectomy for localised prostate cancer in a European population

Andreas Becker*†, Pierre Tennstedt*, Jens Hansen*, Quoc-Dien Trinh†, Luis Kluth‡, Nabil Atassi*, Thorsten Schlomm*, Georg Salomon*, Alexander Haese*, Lars Budaeus*, Uwe Michl*, Hans Heinzer*, Hartwig Huland*, Markus Graefen* and Thomas Steuber*

*Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany, †Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada, and ‡Department of Urology, University-Hospital Hamburg-Eppendorf, Hamburg, Germany

Read the full article
OBJECTIVE

• To address the biochemical and functional outcomes after radical prostatectomy (RP) of men aged <50 years in a large European population.

PATIENTS AND METHODS

• Among 13 268 patients who underwent RP for clinically localised prostate cancer at our centre (1992–2011), 443 (3.3%) men aged <50 were identified.

• Biochemical recurrence (BCR) and functional outcomes (International Index of Erectile Function [IIEF-5], use of pads), were prospectively evaluated and compared between men aged <50 years and older patients.

RESULTS

• Men aged <50 years were more likely to harbour D’Amico low-risk (49.4 vs 34.9%, P < 0.001), organ-confined (82.6 vs 69.4%, P < 0.001) and low-grade tumours (Gleason score <7: 33.1 vs 28.7%, P < 0.001).

• Multivariate Cox regression analysis showed that age <50 years (hazard ratio 0.99; confidence interval 0.72–1.31; P = 0.9) was not a predictor of BCR.

• Urinary continence was more favourable in younger patients, resulting in continence rates of 97.4% vs 91.6% in most recent years (2009–2011) for patients aged <50 vs ≥50 years.

• After RP, a median IIEF-5 drop of 4 points in younger men vs 8 points in older patients was recorded (P < 0.001).

• Favourable recovery of urinary continence and erectile function in patients aged <50 years compared with their older counterparts was confirmed after multivariable adjustment.

CONCLUSION

• Men aged <50 years diagnosed with localised prostate cancer should not be discouraged from RP, as the postoperative rates of urinary incontinence and erectile dysfunction are low and probability of BCR-free survival at 2 and 5 years is high.

 

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Editorial: Radical prostatectomy at young age

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Becker et al. [1] investigated a large sample of young patients (aged <50 years) who underwent radical prostatectomy during a 20-year period in a high-volume European centre. In this study [1], men aged <50 years had a significantly more favourable functional outcome (continence rates [0–1 pads] 97% vs 92%; International Index of Erectile Function [IIEF] score drop of 4 vs 8 points), compared with their older counterparts. Biochemical tumour control was higher in younger patients in univariate (5-year rates 81% vs 70%) but not in multivariate analysis.

In studies in the pre-PSA era, young age at prostate cancer diagnosis was often associated with adverse tumour-related outcome [2]. Possibly, the disadvantage of younger patients was attributable to rapidly growing high-grade tumours causing symptoms at a young age in the absence of a dilution by favourable early detected low-grade cancers. In contemporary patients, the opposite is observed [1]. As the impact of age vanished after controlling for tumour-related prognostic factors reflecting the presence of more favourable disease criteria in younger men, it may be considered likely that PSA-based early detection enriched favourable parameters in the younger subgroup. Altogether, prostate cancer biology is probably not meaningfully associated with age. Outcome differences, even in randomised trials [3, 4], are rather caused by age-related differences in the approach to prostate cancer diagnostics and early detection than in actual biological differences.

The relative favourable functional outcome in younger patients [1] supports early curative treatment in this population. Currently available active surveillance studies have very limited follow-up and were performed mainly in elderly patients with significant comorbidity [5]. Currently, in Germany the further life expectancy in men aged 50 years is ≈30 years [6]. In a contemporary active surveillance study, narrowly half of patients received active treatment within 10 years [5]. Therefore, most men starting active surveillance at an age of 50 years will subsequently receive active treatment. This treatment will then be performed at a greater age where the chances for satisfactory functional recovery are less favourable.

The inferior tumour control rates in patients receiving robot-assisted surgery is another remarkable finding of this study (hazard ratio 1.4, 95% CI 0.99–1.9, P = 0.06 in the multivariate analysis). Although the significance level was narrowly failed, this observation cannot be ignored. It was accompanied by an increased continence recovery rate after robot-assisted surgery suggesting that it may probably not be attributed to the learning curve. Less radical removal of the prostate with more sparing of neurovascular structures and bladder neck might be a conceivable explanation of this phenomenon. In this study [1], the prognostic impact of robot-assisted approach was in a similar range as a positive surgical margin (hazard ratio 1.5, 95% CI 1.4–1.7).

Current clinical guidelines discourage prostate cancer screening in average-risk men aged <50 years [7]. It remains to be seen in which degree these recommendations will affect clinical practice and outcome parameters in this age group in the years ahead.

Read the full article

Manfred P. Wirth and Michael Froehner
Department of Urology, University Hospital ‘Carl Gustav Carus’, Dresden University of Technology, Dresden, Germany

References

  1. Becker A, Tennstedt P, Hansen J et al. Functional and oncological outcomes of patients younger than 50 years treated with radical prostatectomy for localized prostate cancer in a European population. BJU Int 2014; 114: 38–45
  2. Parker CC, Gospodarowicz M, Warde P. Does age influence the behaviour of localized prostate cancer? BJU Int 2001; 87: 629–637
  3. Bill-Axelson A, Holmberg L, Ruutu M et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2011; 364: 1708–1717
  4. Froehner M, Wirth MP. Early prostate cancer – treat or watch? N Engl J Med 2011; 365: 568
  5. Selvadurai ED, Singhera M, Thomas K et al. Medium-term outcomes of active surveillance for localised prostate cancer. Eur Urol 2013; 64: 981–987
  6. Statistisches Bundesamt. Periodensterbetafeln für Deutschland 1871/1881 bis 2008/2010 [Period death tables for Germany 1871/1881 bis 2008/2010]. Wiesbaden 2012. Available at: https://www.destatis.de/DE/Publikationen/Thematisch/Bevoelkerung/Bevoelkerungsbewegung/PeriodensterbetafelnPDF_5126202.pdf?__blob=publicationFile [Website in German]. Accessed 12 July 2013.
  7. Qaseem A, Barry MJ, Denberg TD, Owens DK, Shekelle P; Clinical Guidelines Committee of the American College of Physicians. Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med 2013; 158: 761–769
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Video: RP for younger men – low risk and high survival rate

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Functional and oncological outcomes of patients aged <50 years treated with radical prostatectomy for localised prostate cancer in a European population

Andreas Becker*†, Pierre Tennstedt*, Jens Hansen*, Quoc-Dien Trinh†, Luis Kluth‡, Nabil Atassi*, Thorsten Schlomm*, Georg Salomon*, Alexander Haese*, Lars Budaeus*, Uwe Michl*, Hans Heinzer*, Hartwig Huland*, Markus Graefen* and Thomas Steuber*

*Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany, †Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada, and ‡Department of Urology, University-Hospital Hamburg-Eppendorf, Hamburg, Germany

Read the full article
OBJECTIVE

• To address the biochemical and functional outcomes after radical prostatectomy (RP) of men aged <50 years in a large European population.

PATIENTS AND METHODS

• Among 13 268 patients who underwent RP for clinically localised prostate cancer at our centre (1992–2011), 443 (3.3%) men aged <50 were identified.

• Biochemical recurrence (BCR) and functional outcomes (International Index of Erectile Function [IIEF-5], use of pads), were prospectively evaluated and compared between men aged <50 years and older patients.

RESULTS

• Men aged <50 years were more likely to harbour D’Amico low-risk (49.4 vs 34.9%, P < 0.001), organ-confined (82.6 vs 69.4%, P < 0.001) and low-grade tumours (Gleason score <7: 33.1 vs 28.7%, P < 0.001).

• Multivariate Cox regression analysis showed that age <50 years (hazard ratio 0.99; confidence interval 0.72–1.31; P = 0.9) was not a predictor of BCR.

• Urinary continence was more favourable in younger patients, resulting in continence rates of 97.4% vs 91.6% in most recent years (2009–2011) for patients aged <50 vs ≥50 years.

• After RP, a median IIEF-5 drop of 4 points in younger men vs 8 points in older patients was recorded (P < 0.001).

• Favourable recovery of urinary continence and erectile function in patients aged <50 years compared with their older counterparts was confirmed after multivariable adjustment.

CONCLUSION

• Men aged <50 years diagnosed with localised prostate cancer should not be discouraged from RP, as the postoperative rates of urinary incontinence and erectile dysfunction are low and probability of BCR-free survival at 2 and 5 years is high.

Read more articles of the week
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