Methodological issues in estimating survival in patients with multiple primary cancers: an application to women with breast cancer as a first tumour

<p>Abstract</p> <p>Background</p> <p>Comparing survival of patients with a single tumour and patients with multiple primaries poses different methodological problems. In population based studies, where we cannot rely on detailed clinical information, the issue is disentangling the share of survival probability from the first and second cancer, and their compounded effect. We examined three hypotheses: A) the survival probability since the first tumour does not change with the occurrence of a second tumour; B) the probability of surviving a tumour does not change with the presence of a previous primary; C) the probabilities of surviving two subsequent primary tumours are independent (additivity hypothesis on mortality rates).</p> <p>Methods</p> <p>We studied the survival probabilities modelling mortality rates according to hypotheses A), B) and C). Mortality rates were calculated using Aalen-Johansen estimators which allowed to discount for the lag-time survival before developing a second tumour. We applied this approach to a cohort of 436 women with breast cancer (BC) and a subsequent tumour in the resident population of Turin, Italy, between 1985 and 2002.</p> <p>Results</p> <p>We presented our results in term of a Standardised Mortality Ratio calculated (<it>SMR</it>_<it>AJ</it>) after 10 years of follow-up. For hypothesis A we observed a significant excess mortality of 2.21 (95% C.I. 1.94 – 2.45). Concerning hypothesis B we found a not significant <it>SMR</it>_{<it>AJ </it>}of 0.98 (95% C.I. 0.87 – 1.10). The additivity hypothesis (C) was not confirmed as it overestimated the risk of death, in fact <it>SMRs</it>_{<it>AJ </it>}were all below 1: 0.75 (95% C.I. 0.66 – 0.84) for BC and all subsequent cancers, 0.72 (95% C.I. 0.55 – 0.94) for BC and colon-rectum cancer, 0.76 (95% C.I. 0.48 – 1.14) for BC and corpus uteri cancer (not significant).</p> <p>Conclusion</p> <p>This method proved to be useful in disentangling the effect of different subsequent cancers on mortality. In our application it shows a worse long-term mortality for women with two cancers than that with BC only. However, the increase in mortality was lower than expected under the additivity assumption.</p

Multiple primary tumours: incidence estimation in the presence of competing risks

<p>Abstract</p> <p>Background</p> <p>Estimating the risk of developing subsequent primary tumours in a population is difficult since the occurrence probability is conditioned to the survival probability.</p> <p>Methods</p> <p>We proposed to apply Markov models studying the transition intensities from first to second tumour with the Aalen-Johansen (AJ) estimators, as usually done in competing risk models. In a simulation study we applied the proposed method in different settings with constant or varying underlying intensities and applying age standardisation. In addition, we illustrated the method with data on breast cancer from the Piedmont Cancer Registry.</p> <p>Results</p> <p>The simulation study showed that the person-years approach led to a sensibly wider bias than the AJ estimators. The largest bias was observed assuming constantly increasing incidence rates. However, this situation is rather uncommon dealing with subsequent tumours incidence. In 9233 cases with breast cancer occurred in women resident in Turin, Italy, between 1985 and 1998 we observed a significant increased risk of 1.91 for subsequent cancer of corpus uteri, estimated with the age-standardised Aalen-Johansen incidence ratio (AJ-IR^stand), and a significant increased risk of 1.29 for cancer possibly related to the radiotherapy of breast cancer. The peak of occurrence of those cancers was observed after 8 years of follow-up.</p> <p>Conclusion</p> <p>The increased risk of a cancer of the corpus uteri, also observed in other studies, is usually interpreted as the common shared risk factors such as low parity, early menarche and late onset of menopause. We also grouped together those cancers possibly associated to a previous local radiotherapy: the cumulative risk at 14 years is still not significant, however the AJ estimators showed a significant risk peak between the eighth and the ninth year. Finally, the proposed approach has been shown to be reliable and informative under several aspects. It allowed for a correct estimation of the risk, and for investigating the time trend of the subsequent cancer occurrence.</p

Second primary cancer risk - the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study

Background: There is evidence that cancer survivors are at increased risk of second primary cancers. Changes in the prevalence of risk factors and diagnostic techniques may have affected more recent risks.&lt;p&gt;&lt;/p&gt; Methods: We examined the incidence of second primary cancer among adults in the West of Scotland, UK, diagnosed with cancer between 2000 and 2004 (n = 57,393). We used National Cancer Institute Surveillance Epidemiology and End Results and International Agency for Research on Cancer definitions of multiple primary cancers and estimated indirectly standardised incidence ratios (SIR) with 95% confidence intervals (CI).&lt;p&gt;&lt;/p&gt; Results: There was a high incidence of cancer during the first 60 days following diagnosis (SIR = 2.36, 95% CI = 2.12 to 2.63). When this period was excluded the risk was not raised, but it was high for some patient groups; in particular women aged &#60;50 years with breast cancer (SIR = 2.13, 95% CI = 1.58 to 2.78), patients with bladder (SIR = 1.41, 95% CI = 1.19 to 1.67) and head &#38; neck (SIR = 1.93, 95% CI = 1.67 to 2.21) cancer. Head &#38; neck cancer patients had increased risks of lung cancer (SIR = 3.75, 95% CI = 3.01 to 4.62), oesophageal (SIR = 4.62, 95% CI = 2.73 to 7.29) and other head &#38; neck tumours (SIR = 6.10, 95% CI = 4.17 to 8.61). Patients with bladder cancer had raised risks of lung (SIR = 2.18, 95% CI = 1.62 to 2.88) and prostate (SIR = 2.41, 95% CI = 1.72 to 3.30) cancer.&lt;p&gt;&lt;/p&gt; Conclusions: Relative risks of second primary cancers may be smaller than previously reported. Premenopausal women with breast cancer and patients with malignant melanomas, bladder and head &#38; neck cancers may benefit from increased surveillance and advice to avoid known risk factors