Recurrent PC (non-metastatic, hormone sensitive) after curative therapies exhausted? Here are some clinical trials to look at.

A perplexing situation is what to do after one has tried one or more potentially curative therapies (e.g., prostatectomy plus salvage radiation including pelvic lymph nodes), and there are no detectable metastases, but PSA keeps rising. The TOAD randomized clinical trial demonstrated that survival is improved by starting on hormone therapy (intermittent or continuous) as soon as recurrence is observed. Chemo has not proved to increase survival until after multiple metastases are detected (CHAARTED). Waiting for metastases to appear and spot treating them  has not proved to be beneficial either (see this link).

There may be hope in participating in clinical trials. There aren't many. There is a trial for the earlier use of Xtandi therapies, as well as trials for novel therapeutics, like apalutamide and Prostvac, which have been very promising in early trials. Here's a current list that you may wish to discuss with your medical oncologist:

Advanced hormonal therapies:

Apalutamide:at University of Texas, Houston (a larger trial is no longer recruiting)
Apalutamide/ degarelix/abiraterone at 8 locations
Xtandi at 172 locations
Xtandi at University of Colorado, Denver

Immunotherapy/PARP inhibitor:

Prostvac at NIH
Durvalumab + Olaparib at MSK
Olaparib - recurrent - Johns Hopkins & Thomas Jefferson U.

MAO inhibitor:

Phenelzine at USC

Salvage whole-gland cryoablation after radiation therapy failure

At the 17^th International European Association of Urology Meeting, Joseph Chin of the University of Western Ontario presented his analysis of outcomes of 157 patients treated with whole-gland salvage cryotherapy after primary radiotherapy failure between 1995 and 2004. After a median followup of 117 months:

• ·      10-year overall survival was 76%
• ·      10-year metastasis-free survival was 74%.
• ·      Median biochemical disease-free survival was 56 months.
• ·      10-year biochemical disease-free survival was 34%.
• ·      15-year biochemical disease-free survival was 23%.
• ·      Of the 179 complications, 22 (12%) were serious.

While more than 3 in 4 men had a biochemical recurrence after salvage cryotherapy, it’s not at all clear whether any salvage therapy on this group of patients could have increased survival any better or with fewer complications. As far as I’m aware, this is the longest followup that has been reported in a salvage cryotherapy study, but, paradoxically, its greatest strength is also its greatest weakness. Many of the men treated in this study were selected for salvage treatment before we had advanced imaging techniques that might have identified small distant metastases in many of them. Also, cryotherapy has benefitted from technological advances that have reduced morbidity considerably.

There are many outstanding questions:

• ·      How should patients be selected for salvage therapy after radiation?
• ·      Can we use advanced imaging to eliminate those patients in whom distant metastases have already occurred?
• ·      Did the salvage therapy delay progression?
• ·      Is there a survival advantage to salvage whole-gland cryoablation vs. focal or hemi-gland cryoablation?
• ·      Is there an advantage in terms of treatment morbidity to salvage whole-gland cryoablation vs. focal or hemi-gland cryoablation?
• ·      How does salvage cryo compare to other ablative salvage therapies, salvage radiotherapies, or salvage surgery after radiation failure?