Testosterone Therapy in Men After Radical Prostatectomy for Organ-Confined,Low-Intermediate Prostate Cancer

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* TTh can be given to select men after RP. Longer term outcome needs to be assessed.




Purpose

Testosterone therapy (TTh) in men with T deficiency who have undergone radical prostatectomy (RP) for prostate cancer remains controversial. We aimed to assess the impact of TTh on biochemical recurrence (BCR) rates after RP in men with low-intermediate organ-confined disease.


Materials and Methods

This study included men who underwent an RP at our institution for organ-confined prostate cancer and had grade groups 1 to 3 on RP pathology. A Cox model was created for time to BCR with T use included as a time-dependent covariate, adjusted for age, preoperative PSA, grade group at RP, and the presence of comorbidities. A landmark analysis was used: Patients were included in the analysis if their last PSA in the 18 weeks post operatively was undetectable and they had not had BCR or been lost to follow-up by that point, and follow-up for BCR began at 18 weeks. BCR was defined as a PS ≥ 0.1ng/mL after RP with a second confirmatory rise ≥ 0.1 ng/mL.


Results

The study population included 5199 men after RP, with 198 patients receiving T at any point after RP and 5001 not receiving T. The median age was 59 (IQR, 55-65) and 61 (IQR, 56-66) years, respectively. Men in the T group tended to present with more vascular comorbidities. For those receiving T, clomiphene citrate was prescribed in 49% of men, 32% received transdermal T, and 19% intramuscular T. We found a non significantly decreased risk of BCR associated with the use of T after RP (HR, 0.84; 95% CI, 0.48-1.46; P [ .5), and overall rates of BCR were low, with probability of BCR at 5 years less than 2% in both groups.


Conclusions

TTh can be given to select men after RP. We found no evidence that administration of TTh after RP causes BCR.




* The main limitation of our study is that we only have a medium-term follow-up. It is possible that longer term exposure to T might eventually lead to growth of quiescent PC cells sufficient to cause recurrence. Strengths of our study include a large series of patients, rigorous T testing for TTh patients, and use of a rigorous BCR definition: Most of the prior studies had used a BCR definition of PSA levels between 0.2 and 0.4 ng/mL, which was significantly higher than the 0.1 ng/mL definitions used in this study. Our study is the largest series in the literature to date, but further research including larger numbers of patients receiving TTh with extended follow-up would add support to our conclusions.





CONCLUSION

TTh can be given to select men after RP. Longer term outcome needs to be assessed. Consideration should be given to including higher risk patients in research studies on postprostatectomy TTh.
 

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Table 1. Rates of BCR at 10 y With 95% CIs for Those Taking Testosterone vs Not Taking Testosterone, Separately by the Pathologic Gleason Grade Group, Along With the Estimates for Testosterone Use From the Cox Model for BCR. The Estimate for Grade Group 1 Patients on Testosterone is Based on Only 1 BCR Event
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Figure. Adjusted survival curve showing BCR event rates by group, accounting for the time-dependent nature of testosterone therapy,P [ .5. BCR indicates biochemical recurrence; RP, radical prostatectomy
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Table 2. Association Between Patient and Disease Characteristics and Testosterone Therapy Use. Because Testosterone Therapy Use is a Time-Dependent Covariate, Estimates are Generated From Univariable Cox Proportional Hazards Models for Time From Landmark to Initiation of Testosterone Therapy or Last Follow-Up
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