Androgen Ablation With Salvage Radiation During Post-RP Biochemical Failure - Renal and Urology News

Androgen Ablation With Salvage Radiation During Post-RP Biochemical Failure

Slideshow

  • Unilateral sparing of the neurovascular (NV) bundle is shown. The left NV bundle (arrow) was sacrified due to presence of extracapsular extension, while the right NV bundle was spared.

    Robotic prostatectomy specimen with a Foley catheter through the urethra

    Unilateral sparing of the neurovascular (NV) bundle is shown. The left NV bundle (arrow) was sacrified due to presence of extracapsular extension, while the right NV bundle was spared.

A 65-year-old man was found to have a pT3aN0M0 Stage III Gleason 4+3 prostate cancer (PCa) at the time of robotic prostatectomy. He had negative surgical margins. After extensive counseling, the patient elected against adjuvant radiation therapy. Although initial PSA levels were undetectable, a rise to 0.2 ng/mL was noted 18 months following surgery. The patient is seen by a radiation oncologist to discuss salvage radiation therapy.

Our monthly quiz presents medical cases designed to test your diagnostic skills. The case was prepared by Alexander Kutikov, MD, of Fox Chase Cancer Center in Philadelphia.Reference1. Shipley WU, Seiferheld W, Lukka HR, et al.  Radiation with or without antiandrogen...

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Our monthly quiz presents medical cases designed to test your diagnostic skills. The case was prepared by Alexander Kutikov, MD, of Fox Chase Cancer Center in Philadelphia.

Reference

1. Shipley WU, Seiferheld W, Lukka HR, et al.  Radiation with or without antiandrogen therapy in recurrent prostate cancer. N Engl J Med 2017;376:417-428.

Answer:

E:  Results from RTOG 9601 were recently published in the New England Journal of Medicine.1 Led by William Shipley, MD, from Massachusetts General Hospital in Boston, the study investigated an important question: “Do men who experience biochemical failure after radical surgery for PCa and who undergo additional treatment with salvage radiation therapy benefit from concurrent hormonal blockade?” Clinically, the question is extremely relevant. The trial was initiated in 1998, and after a median 13 years of follow up, this prospective randomized placebo-controlled trial demonstrated an improvement in both overall and PCa survival in men who received 2 years of bicalutamide therapy in addition to radiation (5% and 7.6%, respectively). Furthermore, many more men who did not receive bicalutamide harbored metastatic disease when compared with those who received hormonal blockade (23% vs. 14.5%).

These data illustrate several important points and raise important questions.

  1. Even in these men with biologically aggressive disease who were refractory to surgery, it took over 10 years to see the difference in survival in the 2 groups, underscoring the long natural history of PCa and the challenges associated with conducting effective trials investigating its optimal management.
  2. As the authors of the study acknowledge, since initiation of the trial in 1998, the PCa therapeutic landscape has changed.  Gonadotropin-releasing hormone modulators have now replaced bicalutamide in clinical practice for patients receiving radiation therapy.  Furthermore, during primary radiation therapy, 6 months of hormonal therapy has proven to be sufficient for many patients.  As such, the study’s findings will need to be reconciled with current clinical practice.
  1. On subgroup analysis, some patients did not benefit from 2 years of anti-androgen therapy.  For instance, men with low Gleason score and/or PSA <0.7 at initiation of radiation appeared to not have benefited from androgen ablation.  These data suggest, but do not prove, that the men with lower-risk disease are overtreated by hormone therapy.  Patients with rising PSA after surgery where margins of resection were negative also appeared to not have benefited from androgen ablation.  Indeed, patients with biochemical failure and negative margin status tend to be a higher-risk group since persistent PSA in these men often stems from cell that had left the prostate prior to surgery (i.e., negative margins and rising PSA are more likely to represent systemic metastatic disease and not a local recurrence where radiation therapy would be helpful).
  2. Interestingly, men with Gleason >7 disease did not appear to have benefited from addition of bicalutamide to salvage radiation.  Only 17.3% of men in this cohort harbored Gleason 8-10 disease and, as such, the group may have been too small to demonstrate a statistically significant treatment effect.  Nevertheless, men with localized high-grade disease who present for initial treatment currently face a choice of surgery followed by likely radiation versus radiation with hormone therapy.  The decision to move forward with surgery for some men is influenced by the possibility of avoiding hormone therapy.  Undoubtedly opinions will abound; however, it is unclear how these data from RTOG 9601 can help with decision making for men in such situations.
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