Treatment/Prognosis Flashcards
What is the prognostic significance of PSA-DT after local therapy for prostate cancer?
PSA-DT can help predict MFS and CSS. PSA-DT <3 mos confers a 20-fold higher risk of prostate cancer death than PSA-DT ≥3 mos. For pts with PSA-DT <3 mos, 5-yr cause-specific mortality after biochemical failure is 35% and 75% for Gleason 7 and ≥8 Dz, respectively.
Name 5 prognostic factors associated with a favorable outcome after salvage RT.
Prognostic factors associated with a favorable outcome after salvage RT post prostatectomy: +Margin, low PSA at recurrence, long recurrence-free interval, long PSA-DT, low prostatectomy GS. (Stephenson AJ et al., JCO 2007)
What are the indications for adj RT after prostatectomy, and what studies support its role?
pT3N0 prostate cancer or positive surgical margins. 3 RCTs using these criteria and showed improved 10-yr biochemical PFS with adj RT compared to observation: SWOG 8794, EORTC 22911, and ARO 96-02. The SWOG 8794 study, which has the longest f/u, found an OS benefit with adj RT. Exploratory analyses of the EORTC study suggest that the benefit may be limited to men <70 yo or with +margins after Sg.
Describe the study design and results of the SWOG 8794 RCT that compared adj RT and observation in pts with high-risk features after prostatectomy.
SWOG 8794 enrolled 431 men with pT3N0 prostate cancer or +margin after prostatectomy and randomized to adj RT (60–64 Gy). Adj RT improved MS (15.2 yrs vs. 13.3 yrs). Global QOL was initially worse in the adj RT arm but was similar after 2 yrs of f/u and sup thereafter. (Thompson IM et al., J Urol 2009)
Is there any evidence that salvage RT post prostatectomy improves survival c/w observation?
There is no prospective evidence, but there is retrospective evidence (Trock BJ et al., JAMA 2008). 635 pts s/p prostatectomy with biochemical recurrence were treated either with observation, salvage RT alone, or salvage RT + hormone therapy. Adjusted for prognostic factors, CSS was prolonged in pts who rcvd salvage RT compared to observation, regardless of hormone therapy (5-yr CSS 96% vs. 88%).
Are there randomized data comparing adj vs. salvage RT in men with locally advanced prostate cancer or biochemical recurrence s/p prostatectomy?
No. The 3 randomized trials on adj therapy (SWOG 8794, EORTC 22,911, and ARO 96-02) compared adj RT vs. observation, without strict salvage guidelines at the 1st sign of Dz recurrence. Nonrandomized series on salvage RT appears to produce results somewhat comparable to adj RT. The ongoing RAVES trial (TROG) randomizes men with PSA <0.1 ng/mL postprostatectomy PSA to adj vs. early-salvage RT.
At what threshold should salvage RT be initiated following biochemical failure post prostatectomy?
Based on Stephenson 2007, superior biochemical control following salvage Tx was obtained when salvage Tx was administered at PSA <0.5 ng/mL. This cutoff was later shown to be associated with lower rates of DM, cancer-specific death, and all-cause mortality. (Stish et al., JCO 2016)
What is ultrasensitive PSA and what is its role in the management of biochemical recurrence post prostatectomy?
Ultrasensitive PSA is a newer PSA test with a lower limit of detection of 0.01 ng/mL or less. AUA Guidelines do not recommend calculation of PSA-DT from ultrasensitive measurements. While it has strong NPV, PPV of early PSA-DT may be as low as 40%. The initial validation of PSA-DT as a biomarker was in the context of an assay that only measured PSA >0.2 ng/mL, so the clinical utility of early PSA-DT is still unclear.
What are the appropriate CTV borders for the prostatic fossa?
Below the public symphysis: Ant border is post edge of the pubic bone, post border is ant rectal wall, inf border is 8–12 mm below the vesicourethral anastomosis, and lat borders are levator ani and obturator internus muscles. Above the symphysis: Ant border is post 1–2 cm of the bladder, post border is mesorectal fascia, sup border is cut end of the vas deferens, and lat borders are the sacrorectogenitopubic fascia.
What is the role of pelvic nodal RT in salvage RT post prostatectomy?
The appropriate Tx volume in adj and salvage RT post prostatectomy has not been prospectively determined. Randomized trials in adj RT (SWOG 8794, EORTC 22,911, and ARO 96-02) used small-field RT and did not include regional pelvic nodal irradiation. RTOG-0534 is an ongoing trial looking at extent of pelvic RT, but only in men also receiving hormone therapy.
What should be the RT dose in adj and salvage RT post prostatectomy?
There are no randomized studies addressing the issue of dose in adj and salvage RT post prostatectomy. The ASTRO consensus panel recommends >64 Gy and NCCN recommends 64–72 Gy, with further dose escalation an option for gross LR. SAKK 09/10 is an ongoing trial randomizing men undergoing salvage prostate bed RT to 70 Gy vs. 64 Gy.
Are there randomized data supporting the addition of hormone therapy to salvage RT post prostatectomy?
Yes, 2 phase III RCTs address this question. RTOG 9601 randomized 761 pts with biochemical recurrence post prostatectomy with PSA 0.2–4.0 ng/mL to 64.8 Gy to the prostatic fossa +/– 2 yrs of bicalutamide. 10-yr OS was significantly improved with bicalutamide (82% vs. 78%). However, use of antiandrogen monotherapy and liberal PSA entry criteria may question the applicability of this strategy. GETUG-AFU 16 randomized 743 men with postprostatectomy PSA 0.2–2.0 ng/mL to 66 Gy to the prostatic fossa +/– 6 mos goserelin. 5-yr PFS was significantly improved (80% vs. 62% with ADT). Longer f/u is awaited to assess the impact on OS. The ongoing trials RTOG 0534 and RADICALS are further attempting to address this question.
Is there a role for salvage prostatectomy for biochemical recurrence after RT for prostate cancer?
Yes. For biochemical recurrence after RT for prostate cancer, salvage prostatectomy can provide long-term Dz control in a significant portion of pts. However, salvage prostatectomy is associated with a higher risk of urinary incontinence and rectal injury, though pts treated with modern IMRT may have better outcomes. Careful pt selection is the key. Outcome is better with pts with lower preop PSA. Based on retrospective series, 5-yr PFS is up to 86% for a PSA <4, 55% for a PSA 4–10, and 28% for a PSA >10.
Is there a role for cryotherapy or brachytherapy for biochemical recurrence after RT for prostate cancer?
This is uncertain and there are no prospective studies evaluating these strategies in the setting of biochemical recurrence. Retrospective studies suggest both strategies may be considered as possible salvage options in this setting.
