Surgery or radiotherapy for prostate cancer?

BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g1580 (Published 26 February 2014) Cite this as: BMJ 2014;348:g1580

Re: Surgery or radiotherapy for prostate cancer?

Dear Editor of the BMJ,

Regarding “Comparative effectiveness of radical prostatectomy and radiotherapy in prostate cancer: observational study of mortality outcomes”, BMJ. 2014 Feb 26;348:g1502.

The authors of this article have in a retrospective study addressed the very important subject regarding survival after surgery versus radiotherapy for prostate cancer. They conclude that “for most men with non-metastatic prostate cancer, surgery leads to better survival than does radiotherapy. Younger men and those with less comorbidity who have intermediate or high risk localized prostate cancer might have a greater benefit from surgery.” Although this is a large population based study, we have some major concerns about these conclusions.

The two patient populations in this study are clearly different. In Table 1, almost all clinico-pathological data significantly favor surgery. Subsequent statistical adjustments cannot fully make up for this lack of balance, which has been pointed out by others (1). This leads us to believe that their corrections are unable to adequately adjust for known/unknown factors. Exactly how the populations were matched is not revealed to the reader. If these results represent a true difference in a balanced patient cohort, i.e. that surgical treatment would reduce death in prostate cancer; one would not expect that death due to other causes would be higher in the radiotherapy group as is the case in this study. It suggests that the attempt to perform adjustments was not successful and probably incomplete.

Despite a rather short median follow-up time of 5 years, a clear survival benefit was observed between radiotherapy and prostatectomy even in the low risk group. This further increases our concerns about the results from this study keeping in mind that prostatectomy has not shown better cancer specific mortality as compared to watchful waiting in two large randomized trials for the low risk category, with much longer median follow up times of 10 and 13.4 years, respectively (2, 3). The reason for this discrepancy is unknown but raises concerns about the treatment comparisons made, given the known efficacy of radiotherapy in prostate cancer treatment (4, 5).

Several aspects regarding the data-set are important for the interpretation of the results. Data in a quality register are not monitored and reviewed as compared to, for example, the data in a prospective clinical study which leads to further questions. Did primary treatment mean that it was given with curative intent or is it possible that the radiation doses were given with only palliative intention? An unknown proportion of the surgery patients received adjuvant or salvage radiotherapy. If this parameter was taken into account, would that change the conclusions? The analysis is based on "planned treatment” and not "given treatment". The reciprocity between these entities is not known. This underlines the importance of validating data before drawing strong conclusions. The fact that similar studies (6, 7) with more detailed treatment information have shown conflicting results indicates that the authors should have retrieved treatment data before defining different treatment groups. This is a subject for further analysis. The development and implementation of radiotherapy treatment data registries is ongoing in Sweden which will enable more accurate comparisons of different treatment modalities.

In conclusion we assume that residual confounding, despite the use of propensity scores, has affected the results of this study. This clearly underlines the obvious need for prospective randomized data to adequately compare these treatment modalities. We strongly urge those who treat prostate cancer to make no change in their practices based on this study and suggest that they wait a little longer for more valid data to emerge from two much awaited randomized trials. The recently started SPCG-15, comparing surgery versus radiotherapy in high risk patients, will hopefully solve the issue in the high risk group. Further conclusions in low and intermediate risk patients should await the ProtecT trial. The first report from this study is likely to be published in 2015.

1. Stattin P, Loeb S. "To measure is to know. If you cannot measure it, you cannot improve it": statistical modeling cannot compensate for unmeasured bias. European urology. 2014;65(4):701-3.
2. Bill-Axelson A, Holmberg L, Garmo H, Rider JR, Taari K, Busch C, et al. Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer. New England Journal of Medicine. 2014;370(10):932-42.
3. Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, et al. Radical prostatectomy versus observation for localized prostate cancer. The New England journal of medicine. 2012;367(3):203-13.
4. Widmark A, Klepp O, Solberg A, Damber JE, Angelsen A, Fransson P, et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet. 2009;373(9660):301-8.
5. Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011;378(9809):2104-11.
6. Boorjian SA, Karnes RJ, Viterbo R, Rangel LJ, Bergstralh EJ, Horwitz EM, et al. Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer. Cancer. 2011;117(13):2883-91.
7. Zelefsky MJ, Eastham JA, Cronin AM, Fuks Z, Zhang Z, Yamada Y, et al. Metastasis after radical prostatectomy or external beam radiotherapy for patients with clinically localized prostate cancer: a comparison of clinical cohorts adjusted for case mix. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010;28(9):1508-13.

Competing interests: No competing interests

12 March 2014
Anders Widmark
Professor, Senior Consultant Oncology
Anders Widmark, Adalsteinn Gunnlaugsson, Per Nilsson, Håkan Jonsson, Björn Zackrisson, René Blom, Ingela Franck-Lissbrant, Anthony Zietman, Alberto Bossi, David Dearnaley, Howard Sandler
Umeå University
Cancercenter, 90185, Umeå