Intermediate- and High-Risk Prostate Cancer
Background
Estimate the annual incidence and mortality of prostate cancer in the U.S.
~230,000 Dx of and ~27,000 deaths from prostate cancer annually in the U.S.
Where does prostate cancer rank as a cause of cancer death in men in the U.S.?
Prostate cancer is essentially tied with colorectal cancer as the 2nd most common cause of cancer death behind lung cancer.
What % of newly diagnosed prostate cancer is cT3 or higher?
12%–28% of men with newly diagnosed prostate cancer have cT3 Dz or higher.
What % of newly diagnosed prostate cancer is Gleason ≥7 on Bx?
In the U.S., ~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 U.S., ~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 ng/mL.
In a man with a pre-Bx PSA <4 ng/mL, the risk of Gleason ≥7 is ~PSA × 2.
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.
Workup/Staging
By the D–Amico criteria, which localized prostate cancer pts are considered to have intermediate-risk Dz?
A pt has intermediate-risk prostate cancer if he has any or all of the following 3 risk factors (but no high-risk factors): stage T2b, Gleason 7, and pre-Tx PSA 10–20 ng/mL. (D–Amico A et al., J Urol 2001)
By the D–Amico criteria, which localized prostate cancer pts are considered to have high-risk Dz?
A pt has high-risk prostate cancer if he has any or all of the following 3 risk factors: stage ≥T2c, Gleason ≥8, and pre-Tx PSA >20 ng/mL. (D–Amico A et al., J Urol 2001)
What is the Roach equation that estimates risk of pathologic ECE in prostate cancer pts?
Roach equation for ECE risk:
ECE% = ([3/2] × PSA) + ([Gleason − 3] × 10)
What is the Roach equation that estimates risk of pathologic seminal vesicle involvement in prostate cancer pts?
Roach equation for seminal vesicle risk:
SV% = PSA + ([Gleason − 6] × 10)
What is the Roach equation that estimates risk of pathologic LN involvement in prostate cancer pts?
Roach equation for LN risk:
LN% = ([2/3] × PSA) + ([Gleason − 6] × 10)
The Roach equations were developed from prostate cancer pts who had surgery in which yrs?
The Roach equations were developed from prostate cancer pts who had surgery between 1982–1996 (i.e., mainly in the pre-PSA era). These tools likely overestimate risks in pts diagnosed in the post-PSA era.
What is the sensitivity and specificity of endorectal coil MRI for determining the presence of prostatic ECE?
The estimates for the sensitivity and specificity of endorectal coil MRI as a predictor of prostatic ECE vary widely, between 13%–95% (sensitivity) and 49%–97% (specificity). The experience of the radiologist appears to play an important role in the accuracy of the tool.
What is the sensitivity and specificity of endorectal coil MRI for determining the presence of seminal vesicle invasion by prostate cancer?
The estimated sensitivity of endorectal coil MRI to predict seminal vesicle invasion by prostate cancer varies widely from 23%–80%. The estimates for specificity of seminal vesicle invasion are superior and vary between 81%–99%.
If an endorectal coil 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 endorectal coil MRI as part of the workup for prostate cancer. However, if an MRI is ordered, wait 6–8 wks after Bx to avoid artifact caused by post-Bx hemorrhage.
Treatment/Prognosis
What are the Tx options for a man with localized intermediate-risk prostate cancer?
Tx options for a man with intermediate-risk prostate cancer:
EBRT +/− short-term androgen suppression (AS) (4–6 mos) +/− brachytherapy (brachy) boost
Brachy +/− AS
Prostatectomy (less ideal for pt with >1 intermediate risk factor).
If he has a life expectancy <10 yrs, also consider active surveillance.
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 +/− brachy boost
Prostatectomy (less ideal for high-risk pts)
Estimate the 5-yr biochemical failurefree 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 and 4 + 3 = 7 Dz treated with prostatectomy alone.
After prostatectomy alone, 10-yr bFS is ~60% with Gleason 3 + 4 = 7 and ~33% with 4 + 3 = 7. (Han M et al., Urol Clin N Am 2001)
Estimate the 10-yr bFS for prostate cancer pts with Gleason 8–10 Dz treated with prostatectomy alone.
After prostatectomy alone, 10-yr bFS is ~29% with Gleason 8–10 Dz. (Han M et al., Urol Clin N Am 2001)
Estimate the 10-yr bFS for prostate cancer pts with a pretreatment prostate-specific 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 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. In addition, a longer duration of neoadj therapy (6–8 mos vs. 3 mos) is associated with improvements in these pathologic outcomes. (Kumar S et al., Cochrane Database Sys Rev 2006)
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 Sys 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 is indicated and 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), though 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 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.
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