Treatment/Prognosis Flashcards
Define active surveillance, watchful waiting, and observation.
Active surveillance is the postponement of immediate therapy, with active monitoring and definitive Tx given if Dz progresses. Watchful waiting is traditionally defined as forgoing definitive Tx, does not involve active monitoring, and is typically reserved for those with a short life expectancy. However, in order to disambiguate terms often used interchangeably, current guidelines refer to active surveillance vs. observation. Observation indicates monitoring for progression and offering palliative therap
In men with early-stage prostate cancer, what is the benefit in terms of upfront surgical management vs. watchful waiting?
A Swedish study, SPCG-4, randomized 695 men with T1–T2 prostate cancer (all grades) to radical prostatectomy vs. observation. Sg improved 18-yr incidence of cause-specific death (17.7% vs. 28.7%) and DM (26.1% vs. 38.3%). However, this study was conducted in a pre-PSA screening era and included pts with GS 7–10. (Bill-Axelson A et al., NEJM 2014)
Have any randomized studies compared active surveillance, radical prostatectomy, and EBRT in localized prostate cancer?
Yes, the ProtecT trial (Hamdy FC et al., NEJM 2016) randomized 1,643 men with localized prostate cancer (GS 6–10; T1c–T2) diagnosed by PSA testing to active monitoring (n = 545), Sg (n = 553), or radiotherapy + short-course ADT (n = 545). The primary outcome was prostate-cancer mortality. At a median of 10 yrs of f/u there was no difference in prostate cancer–specific deaths or OS. Metastatic Dz was more common in the active monitoring group (6.3 events per 1,000 person-yrs) than in the Sg (2.4 per 1,000 person-yrs) or radiotherapy (3.0 per 1,000 person-yrs) groups (p = 0.004). 27 men require Sg and 33 men require radiotherapy to prevent 1 pt from having metastatic Dz.
What was the active monitoring protocol in the ProtecT trial?
Serum PSA levels were measured q3 mos in the 1st yr and q6–12 mos following. An increase of at least 50% during the previous 12 mos triggered a review. DRE and repeat Bx were not part of the active monitoring protocol. A less comprehensive active monitoring protocol could have contributed to worse outcomes in the active monitoring group (e.g., metastatic Dz).
What are the 2 primary surgical approaches for prostatectomy and have any trials compared them?
The 2 primary surgical approaches are robotic-assisted radical prostatectomy and radical retropubic prostatectomy. A trial (Yaxley J et al., Lancet 2016) randomized 326 men with prostate cancer to robotic-assisted or retropubic radical prostatectomy and found no statistically significant differences at 12 wks regarding urinary function, sexual function, postop complications or margin status.
What is the premise underlying active surveillance in prostate cancer care?
A majority of men with low-risk prostate cancer would not have any adverse clinical consequences if left untreated. Active surveillance delays definitive Tx for the majority while reserving curative for those with Dz progression.
What f/u procedures are involved in active surveillance? When should pts be referred for definitive management?
PSA no more than q6 mos, DRE no more than q12 mos, prostate Bx no more than q12 mos. MRI may be used to aid in the detection of high-grade Dz. Pts are referred for definitive management for increasing GS, increasing volume (as estimated by # of cores and % of cores involved), or pt preference.
Per 2018 NCCN guidelines what prostate cancer risk groups are appropriate for consideration of active surveillance?
Favorable intermediate-, low- and very low-risk groups.
Per 2018 NCCN guidelines what individuals are appropriate for consideration of observation only?
Very low–, low-, and intermediate-risk prostate cancer with <10 yrs life expectancy.
What % of men with low-grade, early-stage Dz will eventually need definitive management with curative intent b/c of progressive Dz? What is their expected prostate-cancer mortality?
In a prospective cohort study at the JHH of low-risk men undergoing active surveillance, the 10- and 15-yr rates of curative intervention were 50% and 57%, respectively, with a 15-yr prostate-cancer mortality of 0.4% (Tosoian JJ et al., JCO 2015). Similar results were demonstrated in a prospective study from Toronto that also included favorable intermediate-risk Dz with 98.5% CSS (Klotz L et al., JCO 2015).
What 3 standard Tx options are available to an otherwise healthy man with no adverse GI/GU Sx and low-risk group Dz?
Active surveillance
Radical prostatectomy
RT (EBRT and/or brachytherapy)
Does dose escalation improve outcomes in men with low-risk prostate cancer?
Dose escalation improves biochemical FFS in men with low-risk prostate cancer. This has been seen in at least 2 randomized trials that included men with low-risk Dz. PROG 9509 (Zietman AL et al., JCO 2010) compared 70.2 Gy vs. 79.2 Gy and found improved 10-yr biochemical failure (32.2% vs. 16.7%). The MDACC RCT (Kuban D et al., IJROBP 2008) compared 70 Gy vs. 78 Gy and found that dose escalation improved 8-yr freedom from failure (78% vs. 59%). Neither study demonstrated a benefit in cause-specific mortality or OS. RTOG 0126 is a phase III trial comparing 79.2 Gy in 44 fx or 70.2 Gy in 39 fx powered to examine OS. With a median of 7.0 yrs of f/u no differences in OS were reported. (Michalski et al., JAMA Oncology 2018)
Have any trials compared Sg to EBRT for localized prostate cancer?
Yes. The ProtecT trial (Hamdy FC et al., NEJM 2016) showed no differences in death d/t prostate cancer with RP vs. RT + ADT. Pt-reported QOL data (Donovan JL et al., NEJM 2016) showed increased urinary pad use in the RP vs. RT groups at 6 mos (46% vs. 5%) and 6 yrs (17% vs. 4%). Bowel function was similar b/t groups except an increase in bloody stools in the radiotherapy group. 17% and 27% of men could obtain erections adequate for intercourse at 6 yrs in the RP and RT groups, respectively, compared to 67% at baseline.
What data support the use of hypofractionation for localized prostate cancer?
The CHHiP trial (Dearnaley D et al., Lancet 2016) randomized 3,216 men from 71 centers with localized prostate cancer (pT1b–T3aN0M0) to 74 Gy in 37 fx vs. 60 Gy in 20 fx vs. 57 in 19 fx. With a median f/u of 62 mos 60 Gy in 20 fx was noninf to 74 Gy in 37 fx. There were no significant differences in side effects at 5 yrs using 3 clinician- and pt-reported outcome measures. RTOG 0415 (abstract only, ASCO 2016) similarly showed that in men with low-risk prostate cancer, 70 Gy in 28 fx is noninf to 73.8 Gy in 41 fx.
What evidence supports the use of SBRT for localized prostate cancer?
Data supporting SBRT in the Tx of localized prostate cancer are limited to phase I/II studies. A pooled analysis of phase II trials in 1,100 men undergoing CyberKnife to a median dose of 36.25 Gy in 4–5 fx found 5-yr BFFS of 93%. Reported GI and GU QOL returned to baseline within 6 mos following Tx, but toxicity grade was not reported (King CR et al., Radiotherapy and Oncology 2013). A later multi-institutional phase I/II study (Hannan R et al., Eur J Cancer 2016) of 91 low- and intermediate-risk prostate cancer pts treated with up to 50 Gy in 5 fx found 98.6% BFFS at 5 yrs. 4 grade IV late GU/GI toxicities were observed.
