A New Prognostic Tool for Patients Undergoing Radiotherapy plus Upfront Transurethral Resection for Bladder Cancer

Discussion

Considerable efforts have been made to improve the prognoses of patients with bladder cancer (6-10). Many of these patients are not able to withstand radical cystectomy, which is associated with severe complications in almost one-third of patients (3-5). The alternative approach including transurethral resection of the tumour and local radiotherapy with or without radio-sensitising chemotherapy is also aggressive and may result in serious adverse events, mainly of the bladder and the rectum. When selecting a bladder-preserving treatment approach, one should always consider the patient's particular situation, including their survival prognosis. Patients with a short remaining lifespan may not benefit from an aggressive approach with a high radiation dose and concurrent chemotherapy; a shorter radiation program without chemotherapy may be more appropriate. On the other hand, for patients with a more favourable survival prognosis, local and locoregional control of the disease is more important. In these patients, a more aggressive approach including higher radiation doses and chemotherapy appears justified in order to improve the outcome.

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Figure 1.

Comparison of the three groups defined using the prognostic tool based on pack years and Karnofsky performance score (Kaplan–Meier curves). The p-value (univariate analysis) was obtained from the log-rank test.

These considerations make it clear that it is important to know a patient's survival prognosis in order to choose the best treatment regimen for each patient. A prognostic tool designed specifically to estimate the survival of this particular patient group is needed. Such tools have been developed for patients with bladder cancer in other situations, such as locally recurrent and metastatic disease (11, 12). However, a tool for definitive bladder-preserving treatment has been lacking. To close this gap, the present study was performed.

In this study, a prognostic tool for estimation of survival of patients undergoing organ-preserving treatment for bladder cancer was created. It included those clinical parameters that proved to be significant on both univariate and multivariate analyses, namely pack years and KPS. Based on these two parameters, three prognostic groups were designed with significantly different 3-year OS rates and median OS times. For the 6-point group, the 3-year OS rate was 0%, and the median OS duration only 2 months. These patients should be treated with a very short course of radiotherapy without concurrent chemotherapy and may even be considered for best supportive care alone. Patients of the 10-11 point group had a relatively poor 3-year OS rate of 34%. Their treatment regimen should be chosen on an individual basis considering the patient's preference weighing improved local control versus an increased risk of serious adverse events. The radiotherapy dose may be lower than 59.4 Gy in 33 fractions and concurrent chemotherapy may be omitted, depending on the patient's choice. For the 15-point group, the 3-year OS rate was 83%, and the median OS duration 76 months. These patients would likely benefit from a more aggressive approach including a radiation dose of 59.4 Gy in 33 fractions supplemented with concurrent chemotherapy, since these patients live long enough to be at risk of developing a local or locoregional recurrence, which cannot be effectively treated with a second course of radiotherapy or radio-chemotherapy.

When following these recommendations, physicians should be aware that the predictive tool was generated from retrospective data and bears the risk of including hidden selection biases. However, since patients with bladder cancer undergoing organ-preserving treatment are uncommon, prospective trials with a sufficient statistical power cannot be expected in the near future. Moreover, the findings of the present study that a lower number of pack years and a better KPS are significantly associated with longer OS agree with data regarding other oncological situations reported in the literature and, therefore, show consistency (11, 13-15). The fact that a lower number of pack years results in better treatment outcomes was demonstrated for other tumours including head-and-neck cancer (13, 14). A positive association with greater KPS and improved OS was previously found in patients with locally recurrent or metastatic bladder cancer (11, 15).

In conclusion, a prognostic tool was developed to be able to estimate the survival of patients with bladder cancer undergoing a bladder-preserving treatment approach including radiotherapy with upfront transurethral resection of the tumour. This new prognostic tool can improve the individualization of the treatment for this particular group of patients with bladder cancer.