Testosterone recovery in patients with prostate cancer treated with radiotherapy and different ADT duration: Long-term data from two randomized trials.

Abstract

300 Background: To determine the rate and time of testosterone (T) recovery to normal level in patients (pts) with prostate cancer treated with radiotherapy plus 6, 18 or 36 months of androgen deprivation therapy (ADT) and considered cured from their disease. Methods: We randomized 1230 pts with prostate cancer, into two phase III trials: 600 with intermediate risk and 630 with high-risk. We selected those considered cured to avoid subsequent T variations due to reintroduction of ADT for recurrence. We excluded the following pts: no ADT at all (126) or not receiving exactly 6, 18 or 36 months of ADT (69), survival less than one year (21), no T measured at baseline or during follow-up (75), biochemical failure (195) or evidence of metastatic/recurrent disease (137).T recovery rate was compared between baseline normal/abnormal T (values below biochemical normal range) and by ADT duration with Chi-square test or Fisher's exact test. A multivariable logistic regression model to predict the probability of recovering normal T was performed by including normal/abnormal T at baseline, age, Zubrod, comorbidities and ADT duration. A second model was performed by replacing ADT duration with baseline PSA, Gleason score and stage. The median time to T recovery was calculated only on pts who recovered normal T. Results: Results are reported with a median follow-up of 14 years. 607 pts fit the criteria and are available for analysis: 309 pts in the 6 months ADT schedule, 185 in the 18 and 113 in the 36. Overall, 76.7%, 54.6% and 45.1% pts recovered normal T on the 6, 18 or 36 months schedule, respectively (p<0.001). The median time to T recovery was 1.5, 3.1, and 5.1 years for the 6, 18 or 36 months schedule, respectively (p<0.001). 79.7% presented with a normal T at baseline while 20.3% had an abnormal T level. By splitting pts between a normal vs. abnormal presenting T level, the T recovery rate was as follows: 82.1%, 63.3%, and 50% for the normal T cohort, compared to 53.4%, 28.3% and 21.1% for the abnormal T cohort at 6, 18 or 36 months, respectively. There was a significant difference in the overall recovery rate (p<0.001) between normal vs. abnormal T level and at all ADT duration lengths between the two cohorts. In multivariable model, baseline normal T was a strong predictor of T recovery. Older age, diabetes, longer ADT, higher clinical stage, higher PSA and higher Gleason score reduced significantly the chance for T recovery. In pts recovering T post-ADT, except for the 6 months duration (p=0.01), the median time for T recovery was not significantly different between normal or abnormal T at baseline in 18 and 36 months cohorts. Conclusions: Older age, longer ADT and poor disease features are associated with a lower T recovery. Even after adjusting for several variables and ADT duration, a higher T recovery post-ADT is significantly associated with a normal T at baseline.

Prognostic Impact of Prostate-Specific Antigen at 6 Months After Radiotherapy in Localized Prostate Cancer: An Individual Patient Data Analysis of Randomized Trials

“…Key limitations include the small number of patients achieving a PSA <0.1 ng/mL in those treated with RT alone, which greatly decreases the prognostic utility of this cutpoint in such patients, and that most patients were treated before 2000 and may therefore not have received contemporary RT approaches nor novel systemic therapies at the time of metastasis. We also recognize the lack of availability of data pertaining to post-therapy testosterone levels; however, very few patients treated with stADT and none treated with ltADT would have recovered their testosterone by 6 months after RT completion, 16 and therefore, a PSA at this time point would very likely be in the context of suppressed testosterone. We categorized PSA values of 0 in the data from the original trial databases as <0.1 ng/mL, although they may have represented readings below an assay detection limit of <0.2 ng/mL and therefore may have actually represented values between 0.1 and 0.2 ng/mL; however, results using a definition of <0.2 ng/mL were very similar to <0.1 ng/mL, suggesting that this did not significantly affect the results.…”

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate

“…The observed differences in patient-level correlation of BCRFS (or TTBCR) with OS between the three groups of trials may be affected by differential durations of gonadal suppression and post-testosterone recovery subsequent PSA kinetics. [24][25][26] When TTBCR was used rather than BCRFS (meaning that other-cause mortality was censored), correlations eroded significantly at both the patient and trial level. Overall, these findings suggest that the strength of association between BCR and OS varies on the basis of the underlying censoring mechanism used to define the BCR-based end point.…”

2023 American Society of Clinical Oncology Genitourinary (ASCO-GU) Cancers Symposium

“…The second study presented evaluated long-term data on testosterone recovery in patients with intermediate-and high-risk prostate cancer treated with radiotherapy and different durations of ADT. 28 Data from two randomized studies (PCS II and PCS IV) was included. Only patients that were considered cured were included in the analysis.…”