Intermediate and high-risk prostate cancer Flashcards
What % of newly diagnosed prostate cancer is Gleason ≥7 on Bx?
In the United States, ∼1 in 3 of all newly diagnosed prostate cancer in a screened population is Gleason ≥7. (Andriole GL et al., NEJM 2009)
What % of newly diagnosed prostate cancer are Gleason ≥8 on Bx?
In the United States, ∼1 in 10 of all newly diagnosed prostate cancer in a screened population is Gleason ≥8. (Andriole GL et al., NEJM 2009)
Estimate the risk of Gleason ≥7 prostate cancer in a man who has pre-Bx PSA of 4–10 ng/mL? ≥10 ng/mL?
∼1 in 2 men with a pre-Bx PSA of 4–10 ng/mL will have Gleason ≥7 prostate cancer. ∼2 in 3 men with PSA ≥10 ng/mL will have Gleason ≥7 prostate cancer. (Schröder FH et al., J Urol 2000)
In which portion of the prostate is the prostatic capsule not clearly defined?
At the apex of the prostate, the prostatic capsule is not clearly identifiable. Some authors argue that the prostate does not have a true capsule but rather simply has an outer fibromuscular band that continuously transitions to
periprostatic tissues and organs. The transition at the apex is particularly difficult to identify. (Ayala AG et al., Am J Surg Pathol 1989)
In which portion of the prostate is ECE most commonly found?
ECE is most commonly found in the posterolat portion of the prostate at the prostatic neurovascular bundle.
According to the 2018 NCCN guidelines which men are intermediate-risk Dz?
T2b–T2c or GS 3 + 4 = 7 or GS 4 + 3 = 7 or PSA 10–20 ng/mL; no high-risk features
According to the 2018 NCCN guidelines which men are high- or very high–risk Dz?
- High: T3a or GS 8–10 or PSA >20 ng/mL
- Very high: T3b–T4 or primary Gleason pattern 5 or >4 cores with GS 8–10
If a pelvic MRI is ordered as part of the workup for prostate cancer, how long after Bx should it take place?
There is no consensus on the role of pelvic/prostate MRI as part of the workup for prostate cancer nor evidence that it improves outcomes. However, if an MRI is ordered, it is ideally done before Bx or 6–8 wks after Bx to avoid artifact caused by post-Bx hemorrhage.
What are the Tx options for a man with localized intermediate-risk prostate cancer?
Tx options for a man with intermediate-risk prostate cancer according to 2018 NCCN guidelines include:
- EBRT +/– short-term androgen suppression (AS) (4–6 mos) +/– brachytherapy boost
- Brachytherapy alone +/– AS
- Prostatectomy (consider likelihood of indications for postop RT)
- Active surveillance if favorable intermediate risk group
If he has a life expectancy <10 yrs, consider observation.
What are the Tx options for a man with localized high-risk prostate cancer?
Tx options for a man with high-risk prostate cancer:
- EBRT + long-term AS (2–3 yrs) +/– pelvic node RT +/– brachytherapy boost
- Prostatectomy (consider likelihood of indications for postop RT)
Estimate the 5-yr biochemical failure-free survival (bFS) for D’Amico intermediate- and high-risk prostate cancer pts treated with prostatectomy alone.
After prostatectomy alone, 5-yr bFS is ∼65% for intermediate-risk and ∼35% for high-risk prostate cancer pts. (D’Amico A et al., J Urol 2001)
Estimate the 10-yr bFS for prostate cancer pts with cT2b and ≥cT2c Dz treated with prostatectomy alone.
After prostatectomy alone, 10-yr bFS is ∼62% for cT2b, and ∼57% for ≥cT2c. (Han M et al., Urol Clin N Am 2001)
Estimate the 10-yr bFS for prostate cancer pts with Gleason 3 + 4 = 7, 4 +3 = 7, and Gleason 8–10 Dz treated with prostatectomy alone.
After prostatectomy alone, 10-yr bFS is ∼60% with Gleason 3 + 4 = 7, ∼33% with 4 + 3 = 7, and ∼29% with Gleason 8–10. (Han M et al., Urol Clin N Am 2001)
Estimate the 10-yr bFS for prostate cancer pts with a pre-Tx prostatespecific antigen (pPSA) from 10–20 and >20 ng/mL treated with prostatectomy alone.
After prostatectomy alone, 10-yr bFS ∼57% with pPSA 10–20 ng/mL and 48% with pPSA >20 ng/mL are 57% and 48%, respectively. (Han M et al., Urol Clin N Am 2001)
What traditionally classied pts as unfavorable vs. favorable intermediate risk?
Factors that may identify an unfavorable intermediate-risk subgroup include primary Gleason 4 Dz, >50% positive cores, or ≥2 intermediate-risk factors. Retrospectively unfavorable pts had higher rates of PSA failure, DM and cause specific mortality. (Zumsteg ZS et al., Eur Urol 2013)
What are the benefits of neoadj AS prior to radical prostatectomy?
The benefits of neoadj AS prior to prostatectomy include decreased +margin and LN positivity rates. This has been shown in multiple randomized trials.
Why is neoadj AS prior to radical prostatectomy not commonly used?
Despite improvement in pathologic outcomes with neoadj AS prior to prostatectomy, long-term bFS rates do not appear to be improved. This negative result has been found in multiple randomized studies. (Kumar S et
al., Cochrane Database Syst Rev 2006)
What is the role of adj AS therapy after prostatectomy?
In prostate cancer pts found to have node+ Dz after prostatectomy, immediate adj AS improves OS. (Messing EM et al., Lancet Oncol 2006) There appears to be no OS or CSS in node– men after prostatectomy (Wirth MP et al., Euro Urol 2004), although the RCT evaluating this question used only an antiandrogen instead of a GnRH agonist or total AS with both.
What study established the role of adj AS for node+ pts after prostatectomy? What is the main criticism of this study?
Messing EM et al. showed an OS benefit of immediate adj AS vs. observation for node+ prostate cancer pts after prostatectomy (MS 13.9 yrs vs. 11.3 yrs, respectively). The main criticism of this study is that AS was not initiated in the observation arm until clinical Dz progression rather than an elevated absolute PSA or PSA velocity. (Lancet Oncol 2006)
Is active surveillance a reasonable approach in intermediate-risk Dz?
Per the NCCN guidelines 2018, active surveillance is an option for men with favorable intermediate-risk Dz.
Is LDR brachy alone appropriate for intermediate- or high-risk Dz? Describe 1 study that argues against LDR brachy.
Per the American Brachytherapy Society guidelines, LDR brachy alone is not appropriate for high-risk Dz but may be considered for highly selected pts
with intermediate-risk Dz (Davis BJ et al., Brachytherapy 2012). A retrospective study by D’Amico A et al. (JAMA 1998) found that LDR brachy alone was associated with worse 5-yr biochemical progression-free survival (bPFS) compared to prostatectomy and EBRT alone in both
intermediate- and high-risk subgroups. However, several single-institution series suggest that well-selected intermediate-risk pts receiving a high-quality implant have excellent outcomes after LDR brachy alone (5-yr bPFS >95%). (Taira AV et al., IJROBP 2009)
What is the role of neoadj AS and LDR brachy for pts with intermediateor high-risk prostate cancer?
Neoadj AS may be used to cytoreduce large prostates (Nag S et al., IJROBP 1999). However, several large retrospective studies have failed to show that AS improves cancer control outcomes in combination with LDR brachy.
What randomized evidence exists for brachytherapy boost following EBRT for intermediate- and high-risk pts?
Hoskin PJ et al. (Radiotherapy and Oncology 2012) randomized mostly intermediate/high-risk men to 55 Gy in 20 fx vs. 35.75 Gy in 13 fx + HDR boost (2 × 8.5 Gy) and found a 31% reduced (p = 0.01) risk of recurrence with HDR boost without excess toxicity. ASCENDE-RT (Morris WJ et al., IJROBP 2017) gave high-risk men 46 Gy to the whole pelvis (WP) and then randomized them to EBRT boost to 78 Gy vs. LDR boost to 115 Gy and found a 50% risk of biochemical failure in the LDR boost arm (p = 0.004), but no difference in OS at 6.5 yrs median f/u.
What studies support the use of short-course (4–6 mos) AS with EBRT in localized intermediate-risk prostate cancer?
The 1st study to show a benefit to short-course AS in locally advanced prostate cancer was RTOG 8610, although all of these pts were high risk as defined by the D’Amico criteria. None of the published studies of shortcourse AS specifically studied intermediate-risk pts. RTOG 9408 enrolled all risk group pts (but mainly intermediate risk) and found a 10-yr OS benefit to
the addition of short-course AS (Jones CU et al., NEJM 2011). In addition, intermediate-risk pts were included in D’Amico A et al. (JAMA 2004), Laverdiere J et al. (J Urol 2004), and Denham JW et al. (Lancet Oncol 2005;
TROG 96.01), all of which showed improved Dz-specific outcomes with the addition of short-course AS to EBRT. It is unclear whether dose escalation mitigates the benefit of short-course AS in intermediate-risk pts.