Yonsei Med J.  2018 Jul;59(5):580-587. 10.3349/ymj.2018.59.5.580.

Impact of Early Salvage Androgen Deprivation Therapy in Localized Prostate Cancer after Radical Prostatectomy: A Propensity Score Matched Analysis

• Park JW
• Jang WS
• Koh DH
• Ham WS
• Rha KH
• Hong SJ
• Choi YD

• KMID: 2412648
• DOI: http://doi.org/10.3349/ymj.2018.59.5.580

Abstract

PURPOSE
Androgen deprivation therapy (ADT) is used as a salvage treatment for men with biochemical recurrence (BCR) of prostate cancer (PCa) following initial radical prostatectomy (RP). The optimal time at which to begin salvage ADT (sADT) remains controversial. In this retrospective study, we evaluated the efficacy of initiating sADT in patients before prostate-specific antigen (PSA) values met the clinical definition of BCR.
MATERIALS AND METHODS
We identified 484 PCa patients who received sADT for BCR after RP. Median follow-up was 82 months. Propensity score matching was performed based on preoperative PSA level, pathologic T stage, and Gleason score. Patients were assigned to two groups of 169 patients each, based on PSA levels at the time of sADT: Group A (without meeting of the definition of BCR) and Group B (after BCR). Kaplan-Meier survival analyses and Cox regression analyses were performed.
RESULTS
The median PSA level at sADT initiation was 0.12 ng/mL in group A and 0.42 ng/mL in group B. Kaplan-Meier analyses showed that group A had favorable disease progression-free survival (DPFS) and distant metastasis-free survival (DMFS), but did not have better cancer-specific survival (CSS) than group B. In subgroup analyses, group A showed better CSS rates in the non-organ confined PCa group. In Cox regression analyses, early sADT was associated significantly with DPFS and DMFS rates, however, did not correlate with CSS (p=0.107).
CONCLUSION
Early sADT after RP improved DPFS and DMFS. Furthermore, early sADT patients demonstrated better CSS in non-organ confined PCa.

Keyword

Radical prostatectomy; androgen deprivation therapy; prostate specific antigen; salvage therapy

MeSH Terms

Disease-Free Survival
Follow-Up Studies
Humans
Male
Neoplasm Grading
Passive Cutaneous Anaphylaxis
Propensity Score*
Prostate*
Prostate-Specific Antigen
Prostatectomy*
Prostatic Neoplasms*
Recurrence
Retrospective Studies
Salvage Therapy
Prostate-Specific Antigen

Figure

• 

  Fig. 1 Kaplan-Meier curves of DPFS in early sADT group (Group A) and delayed sADT group (Group B). sADT, salvage androgen deprivation therapy. DPFS, disease progression-free survival.

• 

  Fig. 2 Kaplan-Meier curves of DMFS in early sADT group (Group A) and delayed sADT group (Group B). sADT, salvage androgen deprivation therapy. DMFS, distant metastasis-free survival.

• 

  Fig. 3 Kaplan-Meier curves of CSS in early sADT group (Group A) and delayed sADT group (Group B). sADT, salvage androgen deprivation therapy. CSS, cancer-specific survival.

• 

  Fig. 4 Kaplan-Meier curves of CSS in subgroups of early sADT group (Group A) and delayed sADT group (Group B). (A) CSS in low/intermediate-risk PCa, (B) CSS in high-risk PCa, (C) CSS in Gleason score <8 PCa, (D) CSS in Gleason score ≥8 PCa, (E) CSS in organ confined PCa, and (F) CSS in non-organ confined PCa. CSS, cancer-specific survival; PCa, prostate cancer; sADT, salvage androgen deprivation therapy.

Reference

1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67:7–30. PMID: 28055103.

2. Resnick MI. Hormonal therapy in prostatic carcinoma. Urology. 1984; 24(5 Suppl):18–23.

3. Huggins C. Effect of orchiectomy and irradiation on cancer of the prostate. Ann Surg. 1942; 115:1192–1200. PMID: 17858048.

4. National Comprehensive Cancer Network. National Comprehensive Cancer Network clinical practice guidelines in oncology (NCCN®): prostate cancer. ver. 2. Fort Washington (PA): National Comprehensive Cancer Network Inc;2017.

5. Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002; 360:103–106. PMID: 12126818.

6. Messing EM, Manola J, Yao J, Kiernan M, Crawford D, Wilding G, et al. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol. 2006; 7:472–479. PMID: 16750497.

7. Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, DiPaola RS, et al. Survival following primary androgen deprivation therapy among men with localized prostate cancer. JAMA. 2008; 300:173–181. PMID: 18612114.

8. Siddiqui SA, Boorjian SA, Inman B, Bagniewski S, Bergstralh EJ, Blute ML. Timing of androgen deprivation therapy and its impact on survival after radical prostatectomy: a matched cohort study. J Urol. 2008; 179:1830–1837. PMID: 18353378.

9. van den Bergh RC, van Casteren NJ, van den Broeck T, Fordyce ER, Gietzmann WK, Stewart F, et al. Role of hormonal treatment in prostate cancer patients with nonmetastatic disease recurrence after local curative treatment: a systematic review. Eur Urol. 2016; 69:802–820. PMID: 26691493.

10. Ryan CJ, Small EJ. Early versus delayed androgen deprivation for prostate cancer: new fuel for an old debate. J Clin Oncol. 2005; 23:8225–8231. PMID: 16278477.

11. D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998; 280:969–974. PMID: 9749478.

12. Buyyounouski MK, Choyke PL, McKenney JK, Sartor O, Sandler HM, Amin MB, et al. Prostate cancer - major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017; 67:245–253. PMID: 28222223.

13. Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol. 2017; 71:630–642. PMID: 27591931.

14. Kirk D. Timing and choice of androgen ablation. Prostate Cancer Prostatic Dis. 2004; 7:217–222. PMID: 15278095.

15. Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med. 1999; 341:1781–1788. PMID: 10588962.

16. Garcia-Albeniz X, Chan JM, Paciorek A, Logan RW, Kenfield SA, Cooperberg MR, et al. Immediate versus deferred initiation of androgen deprivation therapy in prostate cancer patients with PSA-only relapse. An observational follow-up study. Eur J Cancer. 2015; 51:817–824. PMID: 25794605.

17. Duchesne GM, Woo HH, Bassett JK, Bowe SJ, D'Este C, Frydenberg M, et al. Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. Lancet Oncol. 2016; 17:727–737. PMID: 27155740.

18. Fu AZ, Tsai HT, Haque R, Yood MU, Cassidy-Bushrow AE, Van Den Eeden SK, et al. Mortality and androgen deprivation therapy as salvage treatment for biochemical recurrence after primary therapy for clinically localized prostate cancer. J Urol. 2017; 197:1448–1454. PMID: 28007467.

19. Moul JW, Wu H, Sun L, McLeod DG, Amling C, Donahue T, et al. Early versus delayed hormonal therapy for prostate specific antigen only recurrence of prostate cancer after radical prostatectomy. J Urol. 2004; 171:1141–1147. PMID: 14767288.

20. Taguchi S, Fukuhara H, Azuma T, Suzuki M, Fujimura T, Nakagawa T, et al. Ultra-early versus early salvage androgen deprivation therapy for post-prostatectomy biochemical recurrence in pT2-4N0M0 prostate cancer. BMC Urol. 2014; 14:81. PMID: 25323845.

21. Abugharib A, Jackson WC, Tumati V, Dess RT, Lee JY, Zhao SG, et al. Very early salvage radiotherapy improves distant metastasis-free survival. J Urol. 2017; 197(3 Pt 1):662–668. PMID: 27614333.