Reply to the letter to the editor ‘Age at diagnosis and prognosis among prostate cancer patients treated with radiotherapy: evidenced from three independent cohort studies’ by X. Dong, G. Ma and F. Chen
Authors: A. Pettersson, D. Robinson, H. Garmo, L. Holmberg, P. Stattin
Journal: Annals of Oncology (2018)

We read with great interest the Letter by Dong and colleagues assessing the association between age at diagnosis and prognosis among 3304 men in the Prostate, Lung, Colorectal, and Ovarian Cancer Trial (PLCO) and 56 860 men in the Surveillance, Epidemiology, and End Results (SEER) database treated with radiotherapy for prostate cancer [1.Dong X. Ma G. Chen F. Age at diagnosis and prognosis among prostate cancer patients treated with radiotherapy: evidenced from three independent cohort studies.Ann Oncol. 2018; 29: 2019-2020Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar]. In contrast to our null finding among 14 776 Swedish men in the Prostate Cancer data Base Sweden (PCBaSe) [2.Pettersson A. Robinson D. Garmo H. et al.Age at diagnosis and prostate cancer treatment and prognosis: a population-based cohort study.Ann Oncol. 2018; 29: 377-385Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar], they found a positive association between old age at diagnosis (age 75+ versus 60–64) and poorer prognosis in both PLCO and SEER. A positive association between age at diagnosis and poorer prognosis among men treated with radiotherapy for prostate cancer has previously been reported in a study based on 149 967 men in SEER [3.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: 88-95Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar]. To the best of our knowledge, no previous study has specifically reported on the association between age at diagnosis and prognosis among men in PLCO with prostate cancer treated with radiotherapy. Results from SEER and PCBaSe are not readily comparable for several reasons, as previously discussed [2.Pettersson A. Robinson D. Garmo H. et al.Age at diagnosis and prostate cancer treatment and prognosis: a population-based cohort study.Ann Oncol. 2018; 29: 377-385Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar]. Importantly, the SEER database lack information on key confounding factors including Gleason score, prostate-specific antigen (PSA) and comorbidity at diagnosis. Hence, residual confounding remains a concern. Moreover, the radiotherapy data have been verified to have been given with curative intent in PCBaSe [4.Robinson D. Garmo H. Lissbrant I.F. et al.Prostate cancer death after radiotherapy or radical prostatectomy: a nationwide population-based observational study.Eur Urol. 2018; 73: 502-511Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar] but not in SEER (https://seer.cancer.gov/data/treatment.html). Thus, there is a higher risk of misclassification of the exposure with ensuing bias in SEER than in PCBaSe. Results from PLCO and PCBaSe are also not readily comparable, primarily because of differences in study populations. Whereas PCBaSe is a nation-wide population-based cohort, PLCO is a screening trial. The differences in study populations are reflected in differences in baseline characteristics. For example, in PLCO roughly 3% had T3/T4 tumors and 20% PSA above 10 ng/ml at diagnosis, whereas the corresponding numbers in PCBaSe were about 20% and 50% [1.Dong X. Ma G. Chen F. Age at diagnosis and prognosis among prostate cancer patients treated with radiotherapy: evidenced from three independent cohort studies.Ann Oncol. 2018; 29: 2019-2020Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 2.Pettersson A. Robinson D. Garmo H. et al.Age at diagnosis and prostate cancer treatment and prognosis: a population-based cohort study.Ann Oncol. 2018; 29: 377-385Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar]. That said, an important strength with PLCO is that the study subjects are indeed participants in a screening trial. The impact of PSA screening intensity, which is a potentially powerful confounding factor of the association between age at diagnosis and prognosis among men with prostate cancer, should thus be minimized. The results from Dong and colleagues add to the pool of conflicting data on the association between age at diagnosis and prognosis among men with prostate cancer treated with radiotherapy. We stand by our original conclusion: our findings from PCBaSe do not indicate a strong inherent effect of age on risk of prostate cancer death, but indicate that in current clinical practice, old men with prostate cancer receive insufficient diagnostic workup and subsequent curative treatment and that adherence to clinical guidelines needs to be improved for old men. None declared.