Adjuvant and salvage treatment for prostate cancer

Question 1

In which portion of the prostate is ECE most commonly found?

Answer 1

ECE is most commonly found in the poseterolateral portion of the prostate, near the prostatic neurovascular bundle.

Question 2

What is the ASTRO/American Urological Association (AUA) definition of biochemical recurrence s/p radical prostatectomy?

Answer 2

The AUA definition of biochemical recurrence s/p radical prostatectomy is a serum PSA ≥0.2 ng/mL, confirmed by a 2nd determination also ≥0.2 ng/mL.

Question 3

What is the mean time to PSA nadir after RT for localized prostate cancer?

Answer 3

The mean time to PSA nadir after RT for localized prostate cancer is 18 mos. Though there are contradictory reports, it seems that the rate of decline in
PSA does not appear to correlate with risk of Dz recurrence.

Question 4

What is the Phoenix criterion (2005 consensus panel) for defining biochemical recurrence after RT for localized prostate cancer?

Answer 4

Partly to eliminate concerns about the “backdating” associated with the original ASTRO definition, the Phoenix criterion for defining biochemical recurrence after RT for localized prostate cancer is a PSA rise of ≥2 ng/mL above the PSA nadir, even after the discontinuation of androgen deprivation therapy (ADT). The date of recurrence is the date of the PSA that triggers the definition.

Question 5

What is the concept of “PSA bounce” in pts who rcvd RT for localized prostate cancer? How should it be managed?

Answer 5

After RT for localized prostate cancer, serum PSA typically falls. However, it can rise transiently, called a PSA bounce, usually around 12–18 mos after Tx, and classically associated with pts having undergone brachytherapy. This can occur even without Dz recurrence. Using the Phoenix definition of biochemical failure, a PSA bounce can trigger a false failure in 10%–20% of pts. There is no definitive method to distinguish a PSA bounce from recurrent Dz. The PSA should be rechecked 3–6 mos later and managed accordingly.

Question 6

What is the risk of mets or death following biochemical failure after prostatectomy?

Answer 6

In a prominent series of men who developed biochemical failure post prostatectomy and did not undergo subsequent salvage Tx, the median MFS
was 10 yrs. (Pound, JAMA 1999)

Question 7

For men with rising PSA (and no other Sx of Dz) after definitive local Tx for prostate cancer, what is the utility of imaging studies in the workup?

Answer 7

For men with biochemical-only recurrence after definitive local Tx for prostate cancer, the yield of imaging studies is low. The likelihood of a positive bone scan is <5% if PSA <10 ng/mL, though time to PSA relapse and PSA kinetics can change pretest probability. (18F)-fluorocholine and fluciclovine-(18F) PET/CT may offer improved sensitivity, though further investigation of these tests is warranted.

Question 8

What is the utility of prostate Bx for men with a rising PSA (and no other Sx of Dz) after definitive prostate RT?

Answer 8

For post-RT pts with prostate cancer, TRUS prostate Bx is typically not recommended unless local salvage options are being considered, such as prostatectomy. Bx should be performed at least 18 mos after RT completion.

Question 9

What is the utility of prostate bed Bx for men with a rising PSA (and no other Sx of Dz) after radical prostatectomy?

Answer 9

This is controversial, and most recurrences are at the anastomotic site. Palpable prostate bed nodules should probably be biopsied and perhaps given higher doses of RT.

Question 10

What is the prognostic significance of PSA-DT after local therapy for prostate cancer?

Answer 10

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 PSADT <3 mos, 5-yr cause-specific mortality after biochemical failure is 35%
and 75% for Gleason 7 and ≥8 Dz, respectively.

Question 11

Name 5 prognostic factors associated with a favorable outcome after salvage RT.

Answer 11

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)

Question 12

What are the indications for adj RT after prostatectomy, and what studies support its role?

Answer 12

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

Question 13

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.

Answer 13

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)

Question 14

Is there any evidence that salvage RT post prostatectomy improves survival c/w observation?

Answer 14

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%).

Question 15

Are there randomized data comparing adj vs. salvage RT in men with locally advanced prostate cancer or biochemical recurrence s/p prostatectomy?

Answer 15

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.

Question 16

At what threshold should salvage RT be initiated following biochemical failure post prostatectomy?

Answer 16

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, cancerspecific death, and all-cause mortality. (Stish et al., JCO 2016)

Question 17

What is ultrasensitive PSA and what is its role in the management of biochemical recurrence post prostatectomy?

Answer 17

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 PSADT 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.

Question 18

What are the appropriate CTV borders for the prostatic fossa?

Answer 18

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.

Question 19

What is the role of pelvic nodal RT in salvage RT post prostatectomy?

Answer 19

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.

Question 20

What should be the RT dose in adj and salvage RT post prostatectomy?

Answer 20

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.

Question 21

Are there randomized data supporting the addition of hormone therapy to salvage RT post prostatectomy?

Answer 21

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.

Question 22

Is there a role for salvage prostatectomy for biochemical recurrence after RT for prostate cancer?

Answer 22

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.

Question 23

Is there a role for cryotherapy or brachytherapy for biochemical recurrence after RT for prostate cancer?

Answer 23

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.

Question 24

What is the rate of urinary incontinence and anastomotic stricture with salvage prostatectomy for biochemical recurrence after RT for prostate cancer?

Answer 24

These rates are lower in modern series d/t decreased fibrosis with modern RT techniques and improved surgical techniques. In modern series, the rate of
many acute and late complications is similar to standard prostatectomy. However, there are still significant rates of urinary incontinence (30%–50%) and anastomotic stricture (17%–32%).

Question 25

Name 5 side effects associated with ADT.

Answer 25

Side effects associated with ADT include hot flashes, loss of libido, decreased muscle mass, mild anemia, and loss of bone density.