Summary Patients who were previously treated for prostate cancer with radiation therapy are monitored at regular intervals using a laboratory test called Prostate Specific Antigen (PSA). If the value of the PSA test starts to rise, this is an indication that the prostate cancer is more likely to recur, and the patient may wish to initiate new treatments. Such patients could be helped in making medical decisions by an accurate estimate of the probability of recurrence of the cancer in the next few years. In this paper, we describe the methodology for giving the probability of recurrence for a new patient, as implemented on a web-based calculator. The methods use a joint longitudinal survival model. The model is developed on a training dataset of 2,386 patients and tested on a dataset of 846 patients. Bayesian estimation methods are used with one Markov chain Monte Carlo (MCMC) algorithm developed for estimation of the parameters from the training dataset and a second quick MCMC developed for prediction of the risk of recurrence that uses the longitudinal PSA measures from a new patient.

Purpose To estimate the ratio α/β of Prostate Cancer from the effect of dose of radiation on the long term rise of prostate specific antigen (PSA). Materials and methods Repeated measures of PSA from 5,093 patients treated for localized prostate cancer by external beam radiation therapy (EBRT) were analysed. Patients came from 6 large cohorts. A biphasic linear mixed model described the post-treatment evolution of PSA. The effect of the radiation dose schedule on the long term rate of rise of PSA was estimated from the model. The model adjusted for standard prognostic factors (T-stage, initial PSA and Gleason) and cohort specific effects. Results Adjusted for other factors, total dose of EBRT and sum of squared doses per fraction were associated with long term rate of change of PSA (respectively p=0.0017 and p=0.0003), an increase of each being associated with a lower rate of rise. The ratio α/β was estimated at 1.55 Gy with 95% confidence interval [0.46;4.52]. This estimate was robust to adjustment of the linear mixed model but varied according to which cohorts were included, especially the one bringing hypofractioned schemes. Conclusions Using more than 5,000 patients treated by EBRT and a method that accounts for all the repeated measures of PSA after end of treatment rather than only the time of biochemical recurrence, a very low and precise value for α/β was estimated. This result favors hypofractionated radiation therapy that could better control the tumor with a reduced late toxicity. However outcome data from EBRT studies using higher doses per fraction are still needed to validate this result.

Purpose-Late gastrointestinal and genitourinary morbidity from external beam irradiation used to treat adenocarcinoma of the prostate continue to be a concern of physicians, and patients alike. Additionally for high risk/locally advanced patients the appropriate use of hormonal manipulation in addition to radiation therapy (RT) may increase toxicity. We analyzed three large RTOG studies 85-31, 86-10, and 92-02 to try to address the aforementioned issues.Methods-2,922 patients were accrued with a median follow up of 10.3 years for surviving patients. The RTOG scoring scheme was used to assess GI, GU, and other toxicities. Toxicity reported was grade 3 or higher late toxicity. Patient toxicity level was assessed by study and by treatment type combining RT only vs. RT + short course hormone therapy (STH) vs. RT + long term hormone therapy (LTH).Results-Multivariate analysis reveals that age > 70 was statistically significantly associated with a decrease in late any grade 3+ toxicity (HR= 0.78, p=0.0476) adjusted for treatment type. Comparing treatment type, patients treated with RT+STH had a statistically significant lower probability of grade 3+ GI, GU, and other toxicity compared to RT alone (p = .00006; p=0.0037; p=0.0127, respectively). Patients treated with RT+LTH had a statistically significant lower probability of grade 3+ GU toxicity compared to RT alone (p=0.023).Conclusion-These data show that external beam radiation therapy remains a safe option for locally advanced/high risk prostate cancer, and the use of hormonal manipulation does appear to be protective for GU and GI toxicity depending upon length of treatment.

BACKGROUND The combination of external‐beam radiotherapy and brachytherapy is used commonly to treat men with prostate cancer. In this analysis, the authors examined the rate of biochemical recurrence (BR) and late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity after treatment with external‐beam radiotherapy and brachytherapy in a multiinstitutional, cooperative group setting. METHODS All eligible patients received external‐beam radiotherapy (45 Gray [Gy] in 25 fractions) followed 2 to 6 weeks later by an interstitial implant using iodine‐125 to deliver an additional 108 Gy. BR was defined in 2 ways: according to the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Definition (ACD) and according to the Phoenix definition (PD) (prostate‐specific antigen nadir +2 ng/mL). The Radiation Therapy Oncology Group(RTOG)/European Organization for Research and Treatment of Cancer late radiation morbidity scoring system was used to grade all toxicity. RESULTS One hundred thirty‐eight patients were enrolled, and 130 were eligible for the current analysis. The median follow‐up for surviving patients was 49 months (range, 20–60 months). The 48‐month estimate of late grade ≥3 GU/GI toxicity was 15% (95% confidence interval [95% CI], 8–21%), and the 48‐month estimate of BR was 19% (95% CI, 12–26%) and 14% (95% CI, 8–20%) according to the ACD and PD, respectively. CONCLUSIONS The morbidity observed in this multiinstitutional, cooperative group study was slightly higher than that reported in recent RTOG studies using brachytherapy alone or high‐dose external‐beam radiotherapy. The BR rate observed in this report was similar to that observed with high‐dose external‐beam radiotherapy alone in similar patients. Cancer 2007. © 2007 American Cancer Society.