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Surgery or Radiation in Prostate Cancer?




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I am sure many of you are familiar with the clinical situation I see every week of a man with newly-diagnosed prostate cancer asking me about his options. While we steer many men with low risk prostate cancer towards surveillance nowadays, for those with intermediate or high risk disease intervention is usually their best option, especially if they have a long life expectancy. This gives us the dilemma of whether to recommend surgery or radiotherapy.

In Oxford, we have a long and pioneering history of evidence-based medicine, and I lament the lack of RCTs in this field. The only one, ProtecT, which is being led also by Oxford, will not report before 2016, and will at least in part be subject to volunteer bias. Now, the question of surgery or radiotherapy for prostate cancer is not a new question. Millions of men have undergone these treatments across the globe and over the decades, and many other investigators have evaluated this question.

Most of these previous studies suggest that surgery in indeed superior but the main problem with them is inadequate control for selection bias (what we term in the trade as confounding by indication) – i.e. that men undergoing surgery are fitter and have better prognosis from their cancer point of view than men undergoing radiotherapy, and thus it’s not a fair comparison. Another problem with these previous studies is that the datasets used are not very comprehensive – not all men are included, and we don’t know all their important risk factors. All this makes it difficult to be confident in their results.

What is different about the BMJ study (https://www.bmj.com/content/348/bmj.g1502) is that the dataset and the statistics were top-notch. More than 98% of men diagnosed with prostate cancer in Sweden from 1998 onwards were included, and virtually all important data points were recorded with <2% incomplete data. Men were followed for up to 15 years and 4 different sets of statistical models were done to balance the surgery and radiotherapy groups with each other.

Remarkably, all sets of models came up with the same answer: that surgery led to better survival results than radiotherapy, especially for the men with intermediate and high risk prostate cancer and even more so if they had a long life expectancy. If I were a barrister, I would say this study provides strong evidence to build the case that surgery is a better option in survival terms for the majority of men who need treatment for localized prostate cancer.  Medicine, like law, is never about absolutes, it’s about risk and probability. Can I prove that surgery is better than radiotherapy from this study – no; but there certainly seems a strong case to argue.

The current BJUI Article of the Week is another excellent article on the same subject (https://www.bjuinternational.com/article-of-the-week/prostate-cancer-sun-shines-light-on-surgical-survival/)

You can download Drs Sooriakumaran & Wiklund’s slideshow on their article by clicking here (1.5mb)

Prasanna Sooriakumaran is a robotic prostate & bladder cancer surgeon and academic at Oxford and Karolinska. @PSooriakumaranu

 

  1. Prabhakar Rajan
    The authors of both the BMJ and BJUI papers should be commended on excellent retrospective analyses of the large PCBaSe and SEER datasets, respectively. Both studies have used sophisticated statistical methods to attempt to reduce bias from confounding variables. The conclusions - that surgery leads to better survival than does radiotherapy - are potentially very interesting, although must be interpreted with caution in the context of retrospective analyses. We await, with huge anticipation, the results of the ProtecT study comparing these treatment modalities.
  2. Declan Murphy
    Congrats to PS, Peter Wiklund and all on this huge piece of work. Also to Maxine Sun, Quoc and their superb team for their complementary Article of the Week in BJUI. These papers together do not amount to the randomised evidence we would like to see (and I have a feeling that ProtecT may leave a lot of unanswered questions), however the message that radiotherapy underperforms as a cancer intervention for localised prostate cancer certainly has some momentum. Until we see convincing evidence otherwise, from similarly large datasets with appropriate statistics, surgery must be considered as a more robust cancer intervention, especially for non-elderly men with intermediate and high-risk disease. Congratulations to PS, Maxine and colleagues.
  3. Debashis Sarkar
    It was very nine to know about the result of these studies.As it contain a huge number of patients and long follow-up, and the way of measurement of the data. The swidish study is similar to European geographical area.So there will be no question about the external validity.Again in the canadian study showed-In patients with an estimated Life expectency ≥10 years at initial diagnosis, Radical Prostatectomy was associated with improved survival compared with radiotherapy and observation, regardless of disease stage.Both the study result are nearly similar.Congratulation to PS.We will wait for the Protec T Stusy result.
  4. Christopher Eden
    Sooriakumaran's paper is important not just because it adds to the body of evidence that surgery is more effective than radiotherapy at prolonging the lives of men with prostate cancer, which has been growing since Lu-Yao's seminal study of 59,876 men published in 1997 [1], through Abdollah [2] and Suns’s [3] studies of 404,604 and 67,087 men, respectively, to the present day, but also because it tackles head-on the issue of confounding factors.

    The standard response from the naysayers of these studies is to claim that they are irrelevant because radiotherapy techniques have improved since the men in them were treated and that in the current era higher radiotherapy doses are routinely used. That explanation does not seem credible in this study since Sooriakumaran and colleagues found that the year of treatment had no bearing on the differences observed in this study between survival following radiotherapy and surgery. What should also not be discounted are the improvements in surgical technique that has taken place during this time, including the use of extended pelvic lymphadenectomy in men with intermediate- and high-risk prostate cancer, which has been shown in a randomised controlled trial to improve the cancer-specific survival of men in these risk groups at 7 years following surgery by 12.6% and 20.3%, respectively [4].

    The explanation for the difference in the effectiveness of radiotherapy and surgery in treating prostate cancer may not lie just in their biological and physical effects on the men receiving these treatments. Specifically, evidence continues to grow regarding the extent of the detrimental effect on overall survival produced by the use of neoadjuvant and/or adjuvant hormonal manipulation in patients receiving radiotherapy [5].

    References
    1. Lu-Yao GL, Yao SL. Population-based study of long-term survival in patients with clinically localised prostate cancer. Lancet 1997; 349: 906–910.
    2. Abdollah F, Sun M, Thuret R, et al. A competing-risks analysis of survival after alternative treatment modalities for prostate cancer patients: 1988–2006. Eur Urol 2011; 59: 88–95.
    3. Sun M, Sammon JD, Becker A, et al. Radical prostatectomy vs radiotherapy vs observation among older patients with clinically localized prostate cancer: a comparative effectiveness evaluation. BJU Int 2014; 113: 200–208.
    4. Ji J, Yuan H, Wang L, Hou J. Is the impact of the extent of lymphadenectomy in radical prostatectomy related to the disease risk? A single center prospective study. J Surg Res 2012; 178: 779–788.
    5. Nepple KG, Stephenson AJ, Kallogjeri D, et al. Mortality after prostate cancer treatment with radical prostatectomy, external-beam radiation therapy, or brachytherapy in men without comorbidity. Eur Urol 2013; 64: 372–378.
  5. Matt Cooperberg
    Congratulations on a nice study. However, you're a bit dismissive of the quality of the prior work in this area. We published similar findings in 2010 from CaPSURE (ref 22), as did Zelefsky from MSKCC/Baylor in the same year (ref 17)—you review the more recent ones from PCOS etc as well. These studies did in fact include sophisticated statistical analyses: in the CaPSURE analysis (led by Andrew Vickers at MSKCC) we included both proportional hazards and competing risks regressions, as well as an analysis to quantify the extent of unmeasured compounding which would have to be assumed to explain away the results. This study, as well as the Zelefsky study, also included substantially better detailed risk stratification and adjustment than what is possible using PCBaSe.

    Nonetheless, any confirmatory research with clinically meaningful mortality outcomes on this question is always welcome.

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