Radiation Oncology/Prostate/Recurrence after RT

Salvage treatments for biochemical failure after definitive radiotherapy.

See also: Advanced disease for PSA-only recurrence.

Androgen ablation
Timing of Salvage HT:
 * ICORG 97-01 (Irish Clinical Oncology Research Group) (1997-2001) -- early vs late salvage HT
 * Secondary (retrospective) analysis of a randomized trial. ICORG 97-01 compared short (4 months) vs long (8 months) neoadjuvant HT before RT. RT following HRT, 70 Gy. See also: Adjuvant ADT for trial details.
 * Purpose: compare survival outcomes of early vs late salvage HT. Treatment of biochemical failure was not specified per protocol.
 * Group 1 (early salvage): biochemical failure, started on HT with PSA <= 10, no distant mets. Group 2 (late salvage): BF, started on HT with PSA > 10, no distant mets. Group 3 (late salvage with DM): distant mets.
 * 2013 PMID 22658512 -- "Early salvage hormonal therapy for biochemical failure improved survival in prostate cancer patients after neoadjuvant hormonal therapy plus radiation therapy-a secondary analysis of irish clinical oncology research group 97-01." (Mydin AR, Int J Radiat Oncol Biol Phys. 2013 Jan 1;85(1):101-8.)
 * Conclusion: overall survival was improved for pts with BF treated with early salvage HT.


 * RTOG 85-31 (1987-92)
 * "Non-bulky" trial. Long term (indefinite) HT vs none. See also: Adjuvant ADT for trial details.
 * 2010 PMID 20356687 -- "Timing of Salvage Hormonal Therapy in Prostate Cancer Patients With Unfavorable Prognosis Treated With Radiotherapy: A Secondary Analysis of Radiation Therapy Oncology Group 85-31." (Souhami L, Int J Radiat Oncol Biol Phys. 2010 Mar 29. [Epub ahead of print])
 * Subset analysis, relapsing patients in RT alone arm. Defined early salvage as initiated with PSA <10 and late-salvage as >10. Median F/U 11 and 13 years
 * Outcome: Early salvage significantly improved OS (HR 1.5, SS), no difference in local failure or cancer-specific mortality
 * Conclusion: Early introduction of salvage hormonal therapy improved OS but not CSS. Randomized trial is warranted

Intermittent androgen ablation:
 * Canadian trial - phase II
 * PMID 16783817, 2006 &mdash; "Final results of the Canadian prospective phase II trial of intermittent androgen suppression for men in biochemical recurrence after radiotherapy for locally advanced prostate cancer: clinical parameters." Bruchovsky N et al. Cancer. 2006 Jul 15;107(2):389-95.
 * 103 pts. Each cycle consisted of cyproterone acetate (CA) x 4 wks then Lupron plus CA for a total of 36 wks.
 * Median f/u 4.2 yrs. Time off treatment averaged 53% of total cycle time.

Brachytherapy

 * U.Wisconsin, 2007 (Review) PMID 17685384 -- "Management of prostate cancer recurrences after radiation therapy-brachytherapy as a salvage option." (Allen GW, Cancer. 2007 Oct 1;110(7):1405-16.)
 * Review. Summarizes treatment of 226 pts reported in literature, including 12 pts from this institution not previously reported.
 * Wisconsin experience: 12 pts, treated with brachy (I or Pd) + 3 mo neoadjuvant AA. Median f/u of 45 months after implant.
 * Conclusion: salvage brachytherapy success rates are likely similar to salvage with surgery or cryotherapy.

HDR:
 * UCSF (1998-2005)
 * PMID 17197119, 2006 &mdash; "Feasibility of High-Dose-Rate Brachytherapy Salvage for Local Prostate Cancer Recurrence After Radiotherapy: The University of California-San Francisco Experience." Lee B et al. Int J Radiat Oncol Biol Phys. 2006 Dec 28.
 * 21 pts. 36 Gy in 6 fractions.
 * Conclusion: "feasible and effective"

Prostatectomy
Salvage Prostatectomy:
 * Memorial Sloan-Kettering
 * PMID 12756084, 2003 &mdash; "Salvage radical prostatectomy for recurrence of prostate cancer after radiation therapy." Eastham et al. Curr Urol Rep. 2003 June.
 * Incontinence rates are similar to incontinence rates after up front prostatectomy
 * Note: Most other series report higher incontinence rates in the range of 50%


 * UCSF, 2001 (Review) PMID 11590813 -- "Salvage radical prostatectomy." (Shekarriz B, Urol Clin North Am. 2001 Aug;28(3):545-53.)
 * Review.


 * Baylor, 1995 PMID 7526002 -- "Salvage radical prostatectomy: outcome measured by serum prostate specific antigen levels." (Rogers E, J Urol. 1995 Jan;153(1):104-10.)
 * 40 pts.
 * pT3 or pN+ in 54% (more likely if PSA > 10).
 * Mean 39 months f/u. 2 pts died from PCA, 5 developed DM; none had local recurrence. 5-yr PSA control 55%. (more likely if pre-surgery PSA < 10). In pts with pathologically localized disease (minimal T3), 82% had PSA control.
 * Toxicity: 15% rectal injury (colostomy - 2 pts). Persistent urinary incontinence 58% (corrected with artificial sphincter in 9 of 18).
 * Conclusion: salvage prostatectomy provides excellent control of recurrence cancer; best performed before PSA increases greater than 10-20.

Cryotherapy

 * UK, 2007 (2000-5) PMID 17662081 -- "Salvage cryotherapy for recurrent prostate cancer after radiation failure: a prospective case series of the first 100 patients." (Ismail M, BJU Int. 2007 Oct;100(4):760-4. )
 * 100 pts. Mean f/u 33 mo. 5-yr bRFS 73% (low risk pts), 45% (int), 11% (high)
 * Toxicity: incontinence 13%, erectile dysfunction 86%, recto-urethral fistula 1%.
 * Conclusion: salvage cryo is safe and effective