Prostate Postop

== Post-operative Trials ==

Adjuvant Radiation

  • 3 randomized trials (EORTC and SWOG) have shown bPFS for immediate post-op RT vs observation with salvage RT.
  • indications are ECE(+), margin(+), and SVI(+) for both trials
  • SWOG 8794 (Swanson) did show a trend towards OS.
    • 10-RFS 52.6% vs 39.3% p = 0.06.
    • Overall Survival 60.7% vs. 66.8% p = 0.16.
  • EORTC trial 22911 - Bolla[4]
    • bPFS 74% vs 53% favoring RT
    • 5-locoregional failure was 5·4% vs 15·4%, favoring RT
  • ARO 96-02/AUO AP 09/95
    • significant PFS 81% vs 61%

Salvage Radiation

Patterns of Failure

  • Biochemical failure occur 3-5 years before clinical relapse. (Pollack, et al. Cancer 1994 & Paulson DF. J Urol 1994)
  • > 50% biochemical failure with positive margins at surgery.(Connolly JA, et al. Urology 1996 & Shekarriz B, et al. Urology 1999)

Time to Death after Biochemical Failure[3]

  • The median actuarial time to metastases was 8 years from the time of PSA level elevation. In survival analysis, time to biochemical progression (P<.001)
  • Once men developed metastatic disease, the median actuarial time to death was 5 years
  • men with biochemical recurrence have 13 years of median survival.

Indications: Those likely to have local recurrence (thus benefit most from EBRT)

  • PSA failure

— PLUS —

  • Doubling time > 6 months
  • Recurrence > 1 to 2 year
  • Gleason score < 8
  • LN (-)
  • no SV invasion

Results

  • No randomized trials for biochemical relapse

Multiple observational case studies haves shown [1]

  • median RT dose of 64.8 Gy
  • 45% have biochemical controla at 5 years
  • RT may be especially beneficial in PSA > 1.0 ng/mL.[2]

Timing

  • preradiotherapy of < 2 ng/ml had significantly improved PFS than ≥ 2 ng/ml[6]
  • ASTRO consensus panel concluded PSA < 1.5 ng/mL would predict favorable outcome.[7]
  • For adjuvant cases with incontinence, wait for incontinence to improve to a plateau but not beyond PSA of 2. (my thoughts)

Field size for Adjuvant/ Salvage RT

  • The two published randomized trials (SWOG 8794 by Swanson and EORTC 22911 by Bolla) that demonstrate reduced biochemical recurrence with postoperative radiotherapy in high risk prostate cancer use treatment volumes that are smaller than whole pelvis and neither trial used ADT with radiotherapy.

SWOG 8794 Field

  • 9x9 or 10x10 Field with following borders
    • The inferior margin of this field will be the lower border of the ischial tuberosities
    • The lateral fields should extend from the level of the mid rectum to the mid symphysis.
    • The use of an indwelling bladder catheter with contrast in the balloon or retrograde urethrography is mandatory for simulation.
    • Specific instruction should be made in the treatment sheets to assure a full bladder during delivery of treatments.

Consensus CTV[8]

postop

Field Boundaries for 3D and IMRT treatments

  • The inferior boundary was 8-mm below the VUA (anastomosis) or the top of the PB (whichever is most superior).
  • The anterior, caudal boundary was the posterior edge of the symphysis pubis up to the top of the symphysis pubis.
  • The anterior, cranial boundary was the posterior 1.5 cm of the bladder wall.
  • The lateral, caudal boundary was the medial border of the levator ani and obturator internus.
  • In the caudal aspect of the surgical volume, the pelvic muscles bound the lateral dissection plane.

Standford Review

  • High Risk:
    • Gleason score of ≥ 8
    • preoperative PSA >20 ng/mL
    • SV+ or ECE+, or LN+
  • retrospective review from Stanford showed whole pelvic radiotherapy was associated with lower rates of biochemical recurrence in patients with higher risk features.
  • Furthermore androgen deprivation therapy reduced biochemical recurrence with whole pelvic radiotherapy; but not in patients treated with small field radiotherapy.[5]
Bibliography
1. Gunderson L, Tepper J: Clinical Radiation Oncology. 2nd ed. China: Elsevier 2007.
2. Teh BS, Mai WY, Augspurger ME, Uhl BM, McGary J, Dong L, Grant WH 3rd, Lu HH, Woo SY, Carpenter LS, Chiu JK, Butler EB. Intensity modulated radiation therapy (IMRT) following prostatectomy: more favorable acute genitourinary toxicity profile compared to primary IMRT for prostate cancer. Int J Radiat Oncol Biol Phys. 2001 Feb 1;49(2):465-72. Erratum in: Int J Radiat Oncol Biol Phys 2001 Apr 1;49(5):1529. PMID: 11173142
3. Pound, Charles R. MD; Partin, Alan W. MD, PhD; Eisenberger, Mario A. MD; Chan, Daniel W. PhD; Pearson, Jay D. PhD; Walsh, Patrick C. MD Natural History of Progression After PSA Elevation Following Radical Prostatectomy. JAMA. 281(17):1591-1597, May 5, 1999.
4. Michel Bolla, Hein van Poppel, Laurence Collette, Paul van Cangh, Kris Vekemans, Luigi Da Pozzo, Theo M de Reijke, Antony Verbaeys, Jean-François Bosset, Roland van Velthoven, Jean-Marie Maréchal, Pierre Scalliet, Karin Haustermans, Marianne Piérart. Postoperative radiotherapy after radical Prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet 2005; 366: 572–78.
5. Spiotto MT, Hancock SL, King CR. Radiotherapy after prostatectomy: improved biochemical relapse-free survival with whole pelvic compared with prostate bed only for high-risk patients. Int J Radiat Oncol Biol Phys 2007; 69(1):54-61.
6. Stephenson AJ, Shariat SF, Zelefsky MJ, Kattan MW, Butler EB, Teh BS, Klein EA, Kupelian PA, Roehrborn CG, Pistenmaa DA, Pacholke HD, Liauw SL, Katz MS, Leibel SA, Scardino PT, Slawin KM. Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. JAMA. 2004 Mar 17;291(11):1325-32.
7. Cox JD, Gallagher MJ, Hammond EH, Kaplan RS, Schellhammer PF, American Society for Therapeutic Radiology and Oncology Consensus Panel. Consensus statements on radiation therapy of prostate cancer: guidelines for prostate re-biopsy after radiation and for radiation therapy with rising prostatespecific antigen levels after radical prostatectomy. J Clin Oncol. 1999;17:1155-1163.
8. WILTSHIRE et al., Int. J. Radiation Oncology Biol. Phys., Vol. 69, No. 4, pp. 1090–1099, 2007
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