Prostate Cancer Flashcards
What the RECOMMENDATION for PSA screening < 40 yo?
GUIDELINE STATEMENT 1
Do NOT
Low prevalence of CaP, no evidence of screening benefit
For ages 40-54 what RECOMMENDATIONS for PSA for CaP screening?
GUIDELINE STATEMENT 2
Do NOT perform
*not studied sufficiently in PLCO and ERSPC trials
UNLESS shared decision making d/ higher risk:
- AA race
- Family hx of metastatic/lethal adenocarcinoma(prostate, male/female beast cancer, ovarian, pancreatic) spanning multiple generations, multiple first degree relatives at young ages
What does the panel RECOMMENDED for PSA screening for ages 55-69?
GUIDELINE STATEMENT 3
Shared decision making to proceed
Multiple approaches subsequent to PSA to determine need for second biopsy (no proof of utility as primary screening tests)
**urine, serum biomarkers, imaging, risk calculators to help detect men harboring CaP
What does the panel offer and OPTION for PSA screening frequency?
GUIDELINE STATMENT 4
To reduce harms, interval q 2 years or more may be preferred over annually (can be individualized by baseline PSA)
Goteborg data→rescreening every 4 years not likely to miss curable CaP among men PSA < 1.0
What are the risks of prostate cancer screening?
- Psychological
- Hematuria
- Hematochezia
- Hematospermia
- Dysuria
- Retention
- Pain
- Infection
- Over-diagnosis
- Over treatment
- Transient ED
Describe some elements included in SDM for PSA screening for CaP?
- Putative mortality benefit of screening (overall 3% risk of dying)
- Description of options after abnormal PSA
- Likelihood of FP and FN (no screening test perfect, can be elevated for many reasons, PLCO trial annual screening no advantage over biannual in regards to mortality)
- Description of subsequent tests needed
- Harms of screening (additional procedures, hospitalizations, sepsis)
- Information about prostate gland anatomy an function
- CaP incident and mortality
- Treatment options for early and late CaP
- Complications of treatment options
Current AUA guidelines recommend which abx for prostate biopsy?
1 dose of either FQ OR 1st/2nd Gen Cephalosporin +/- Aminoglycoside OR 3rd Gen Cephalosporin
Aztreonam (if resistance)
Local antibiogram
Rectal swab can be considered (hx of resistance, travel, FQ in past 6 mo, healthcare worker)
List the grade groups for CaP:
- Grade Group 1: Gleason 3+3
- Grade Group 2: Gleason 3+4
- Grade Group 3: Gleason 4+3
- Grade Group 4: Gleason 8 (4+4, 3+5, 5+3)
- Grade Group 5: Gleason 9-10 (4+5, 5+4, 5+5)
Prostate cancer T1 staging
T1a → <5% of tissue removed, incidental during unrelated sx
T1b → >5% of tissue removed, incidental during unrelated sx
T1c → cancer found on biopsy, usually related to elevated PSA
Prostate cancer T2 staging
T2 → prostate cancer completely inside gland
T2a → in only < 50% of one lobe
T2b → in > 50% of one lobe
T2c → cancer in both lobes
Prostate cancer T3 staging
T3 → cancer broken through capsule
T3a → broken through capsule
T3b → spread to SV
Prostate cancer T4 staging
T4 → spread to other organs nearby (rectum, bladder, levator muscles, pelvic wall)
CaP Risk Stratification → Low Risk
CaP Risk Stratification → Intermediate Risk
CaP Risk Stratification → High Risk
At CaP diagnosis, it is a STRONG RECOMMENDATION to utilize SDM, incorporating these key elements:
GUIDELINE STATEMENT 1 (CLINICALLY LOCALIZED CAP)
- Risk category
- Patient values and preferences
- Life expectancy
- Pre-treatment General functional and GU sxs
- Expected post-treatment functional status
- Potential for salvage tx
EXPERTS suggest importance of counseling in regards to what factors at the time of CL CaP Dx?
GUIDELINE STATEMENT 2
Modifiable Health-Related Risk Factors
Smoking
Obesity
(Also consider frailty)
Clinicians are RECOMMENDED to encourage patients to meet with whom at time of dx of CaP?
GUIDELINE STATEMENT 3
Different prostate cancer specialists
Urology
Radiation Oncology
Med Oncology
Effective SDM at time of CaP dx requires clinicians to inform patients of what to make proper treatment decisions?
GUIDELINE STATEMENT 4
Immediate and LT morbidity or side effects of proposed treatment decisions
Active surveillance: preserves QOL until Surgery/XRT necessary, declines in urinary, bowel, sexual function over time with age, anxiety
Sx: (immediate) bleeding, infection, pain, (longer term) ED, UI, stricture, bowel problems, death (<0.1%)
XRT: (immediate) urinary irritation, bowel irrigation, GI effects (longer term) UI, ED, secondary cancer, radiation cystitis
Experts suggest clinicians SHOULD inform patients to participate in what additional measure at time of CaP?
GUIDELINE STATEMENT 5
Clinical trials (based on eligibility and access)
At time of dx for low risk or very low risk CL CAP, what imaging is RECOMMENDED?
GUIDELINE STATEMENT 6
Clinician should NOT perform CT A/P or Bone scans
(no evidence to support need for staging)
Clinicians should RECOMMEND which initial tx for very-low risk CL CaP?
GUIDELINE STATEMENT 7
Active Surveillance
(limited or no metastatic potential, major risk serial bx → at 3-5 year intervals after confirmatory bx)
Reminder:
- PSA <10
- GG1 (Gl 6)
- T1-T2a
- <34% biopsy cores positive
- no core >50% involved
- PSA density <0.15
Clinicians should RECOMMEND which initial tx for low risk CL CaP?
GUIDELINE STATEMENT 8
Active surveillance as preferable care option
(regardless of life expectancy)
**Higher volume disease >50% of cores positive or larger lesions on MRI, while still low risk, may benefit from tx
Reminder:
- PSA < 10
- Grade Group 1
- T1-T2a
Clinicians should RECOMMEND which initial tx for select low risk CL CaP?
GUIDELINE STATEMENT 9
Definitive tx RP or XRT
High probability of progression on AS (PIVOT, ProtecT→small reduction in progression)
Clinical Predictors:
PSA denisty >0.15 (2x risk)
Obesity (3 x risk)
AA race
extensive Gl 6 on systematic cores
FHx of aggressive CaP or early mets
If a patient chooses RT for low-risk CL CAP, what is RECOMMENDATION regarding ADT?
GUIDELINE STATEMENT 10
NO ADT with RT
**Exception → reducing size prostate for brachytherapy
If a patient is considering whole gland cryotherapy for low-risk CL CAP, what is RECOMMENDED counseling?
GUIDELINE STATEMENT 11
A/E are considerable: ED, UI, LUTs, bowel sxs, AUR, urethral sloughing
Survival benefit not shown when compared to AS
If a patient is considering focal therapy of HIFU for low-risk CL CAP, what is RECOMMENDED counseling?
GUIDELINE STATMENT 12
These intervention are NOT the standard of care
*Fails to improve survival outcomes or provide comparable QOL, insufficient data to support
Clinicians should RECOMMEND which initial tx for low risk CL CaP with life expectancy < 5 years?
GUIDELINE STATEMENT 13
Watchful waiting/observation
Palliative, non-aggressive intent→no bx
What is EXPERT consensus for patients with low risk CL CaP considering AS in regards to tissue based genomic biomarkers ?
GUIDELINE STATEMENT 14
Have not shown a clear role in selection of candidates for AS
3 approved by FDA:
- Genomic Classifier (GC)–22 marker based on RNA → high score on bx associated with increased risk of mets
- Genomic Prostate Score (GPS)–12 cancer genes, 20 point increase associated with SS increase HG or non-organ confined dz
- Cell Cycle Progression (CCP)–31 cell cycle genes–increased denotes HR disease
At time of dx for UNFAVORABLE intermediate risk CL CAP, what imaging is should be considered by EXPERT OPINION?
GUIDELINE STATMENT 15
CT A/P or MRI prostate or pelvis and Bone Scan (18F NaFl PET/CT or PMSA considered but not standard in US)
Baseline staging if 2 or more: palpable nodule on DRE (stage T2b/c), Gl 7, or PSA >10
Reminder:
- PSA 10-20 OR
- GG 2-3 OR
- T2b-c
- Favorable GG1 (with PSA 10 - <20) or GG2 (with PSA <10)
- Unfavorable: GG2 (either PSA 10 - <20) or T2b-c OR GG3 (PSA < 20)
At time of dx for intermediate risk CL CAP, what tx is RECOMMENDED?
GUIDELINE STATEMENT 16
RP or XRT+ADT
Patient with FAVORABLE intermediate risk CL CAP, what counseling is RECOMMENDED regarding RT and ADT?
GUIDELINE 17
Can be tx with RT alone, but less evidence than in combination with ADT
Unfavorable should especially be considered for ADT
Reminder:
- PSA 10-20 OR
- GG 2-3 OR
- T2b-c
- Favorable GG1 (with PSA 10 - <20) or GG2 (with PSA <10)
- Unfavorable: GG2 (either PSA 10 - <20) or T2b-c OR GG3 (PSA < 20)
Patients with intermediate risk CL CAP, what other tx options can be considered besides RP or RT?
GUIDELINE 18, 19, 20, 21
MAY consider Cryosurgery (limited to 1 RCT) → whole gland may be appropriate if contraindications to RP or RT
MAY offer AS → favorable int risk CL→ inform higher risk mets compared to definitive tx (benefit MRI + target bx)
Watchful waiting < 5 years life expectancy (no AS, no overall improvement in life expectancy with intervention)
HIFU → not the standard options because comparative evidence lacking
At time of dx for high risk CL CAP, what imaging is A CLINICAL PRINCIPAL?
GUIDELINE STATEMENT 22
CT/MRI and Bone Scan
Reminder:
- PSA >20 OR
- GG 4-5 OR
- _>_T3
Clinicians should RECOMMEND which initial tx options for high risk CL CaP?
GUIDELINE STATEMENT 23
RP or RT + ADT
GUIDELINE STATMENT 24, 25, 26
should NOT recommend AS
Watchful waiting only if asx < 5 life expectancy
NO cryotherapy or HIFU (outside clinical trial)
NO primary ADT (unless limited life expectancy and local sxs)
In addition to treatment, what do EXPERTS suggest for high-risk CL CaP at time of dx?
GUIDELINE STATEMENT 27
consider referral for genetic counseling for patient and families
when high risk and strong fhx of specific cancers (breast, ovarian, pancreatic, GI tumors, lymphoma)
*Germline DNA repair mutations
Describe AS CLINICAL PRICIPALS AND RECOMMENDATIONS:
GUIDELINE STATEMENT 28
CL CaP pts who elect AS should have accurate disease staging including systematic bx with US or MRI
(10-12 core with some targeted per DRE or MRI)
GUIDELINE STATEMENT 29
Routine PSA and DRE
optimal schedule not est, but ProtecT suggests q 3 mo x year 1, q3-6 subsequently
GUIDELINE STATEMENT 30
Confirmatory bx within initial 2 years and surveillance bx thereafter (some protocols recommend repeat bx before committing to AS or w/in 6 mo)
GUIDELINE STATEMENT 31
Consider MP Prostate MRI as part of AS (improve retention by reducing need for bx)
GUIDELINE STATEMENT 32
Tissue based genomic markers have NOT shown clear role in AS and are not necessary for f/up
*(ex. Prolaris, Oncotype Dx, Decipher Score)
GUIDELINE STATEMENT 33
Offer definitive tx when develop adverse reclassification (growth, rises in psa, changes in density, upstaging)
*PIVOT and ProtecT, 20% and 50% pts on AS received definitive tx by 10 years
What is RECOMMENDED that clinicians inform patient’s about outcomes, preparation, and types of RP for CL CaP?
GUIDELINE STATEMENT 34
Younger or healthier men are more likely to experience cancer control from RP than older men
*<65 yo or >10 year life expectancy
GUIDELINE STATEMENT 35
Open and RALP offer similar cancer control, continence, and sexual recovery
GUIDELINE STATEMENT 36
RALP or perineal techniques are associated with less blood loss than RRP
GUIDELINE STATEMENT 37
Nerve-spring is associated with better EF (50-95% erections)
GUIDELINE STATEMENT 38
NOT tx with neoadjuvant ADT or other systemic tx (outside clinical trial)
GUIDELINE STATEMENT 39
Older men experience higher rates of permanent ED and PPI compared to younger men
What do EXPERTS suggest for CL CaP undergoing RP in regards to PLND?
GUIDELINE STATEMENT 40
Consider for any
RECOMMENDED for unfavorable intermediate and high risk
Counsel for complications (i.e. lymphocele→ 0.4-16 % incidence, drain +/- sclerosis, occasional MIS marsupialization)
What is RECOMMENDED for adjuvant ADT after RP?
GUIDELINE STATEMENT 41
unfavorable intermediate and high risk advised of r/b/a of adjuvant ADT when locally extensive CaP found during sx
What types of RT are RECOMMENDED for low risk CL CAP?
GUIDELINE STATEMENT 42
EBRT OR brachytherapy
What types of RT are RECOMMENDED for favorable intermediate risk CL CAP?
GUIDELINE STATEMENT 43
EBRT or brachytherapy ALONE or in combination +/- ADT
Reminder:
- PSA 10-20 OR
- GG 2-3 OR
- T2b-c
- Favorable GG1 (with PSA 10 - <20) or GG2 (with PSA <10)
- Unfavorable: GG2 (either PSA 10 - <20) or T2b-c OR GG3 (PSA < 20)
What protocol of RT and tx are RECOMMENDED for high risk CL CAP? What are a/e?
GUIDELINE STATEMENT 44
24-36 mo of ADT in adjunct to EBRT alone or EBRT + brachytherapy
GUIDELINE STATEMENT 45
use of ADT with RT increases a/e on EF and systemic a/e (hot flashes, dec bone mineral density, gynecomastia, depression, fatigue, and weight gain)
What type of EBRT is RECOMMENDED for any risk category of CL CaP?
GUIDELINE STATEMENT 46
consider moderate hypofractionation (without nodal therapy)
GUIDELINE STATEMENT 48
Proton beam therapy offers no clinical advantage over other forms of therapy
For CL CaP patient with obstructive LUTS which is RECOMMENDED in regards to treatment?
GUIDELINE STATEMENT 47
Surgical approaches
Discourage with volume >60 g
If RT for these patient or they have had previous large TURP, low dose brachytherapy should be discouraged
GUIDELINE 49
Brachytherapy has similar effects as EBRT with regard to EF and proctitis, BUT can exacerbate obstructive sxs
When is whole gland cryosurgery a possibility for treatment per EXPERT opinion? What should patients be informed in regards to this treatment and a/e?
GUIDELINE STATEMENT 50
Low- and intermediate risk CL CaP when RP or RT d/ comorbidities is not possible but > 10 years life expectancy
(max recommended 60 g)
GUIDELINE STATEMENT 51
Cryosurgery has similar PFS as non-dose escalated EBRT + ADTin low- and intermediate-risk dz
Conclusive comparison of mortality lacking
GUIDELINE STATEMENT 52
TURP defects are relative contraindication d/t increased risk of urethral sloughing
GUIDELINE STATEMENT 53
Utilize a 3rd or higher generation, argon-based system (double freeze-thaw cycle)
GUIDELINE STATEMENT 54
Unclear +/- ADT improves cancer control, can reduce prostate size to facilitate tx
(>40g, consider 3-6 mo of ADT)
GUIDELINE 55
ED is expected
GUIDELINE 56
A/E include UI, irritative, and obstructive urinary sxs (sloughing, fistula, bowel effects)
What should clinician inform patient with CL CaP considering focal therapy or HIFU?
GUIDELINE STATEMENT 57
these tx options lack evidence of efficacy
GUIDELINE STATEMENT 58
approved by FDA for destruction of prostate tissue, not explicitly for CaP
GUIDELINE STATEMENT 59
tumor location may influence oncologic outcome (apex avoided for morbidity risks cancer persistence)
GUIDELINE STATEMENT 60
CaP is often multifocal, focal therapy may not be curative and further tx needed
What should clinicians inform patients regarding long term secondary effects of RP, cryotherapy, and RT?
GUIDELINE STATEMENT 61
ED occurs, lacking ejaculate, preserved orgasm (no sexual dysfunction with observation)
GUIDELINE STATEMENT 62
Long term obstructive or irritative sxs for AS, RT whereas RP can relieve LUTs
GUIDELINE STATEMENT 63
Whole gland cryotherapy associated with worse sexual side effects and similar urinary/bowel a/e as RT
GUIDELINE STATEMENT 64
PPI occurs in most patients and persists long-term in small but significant subset (more than AS or RT)
GUIDELINE STATEMENT 65
Temporary proctitis s/p RT persists in some patient in LT (rare in AS or RP)
What is RECOMMENDED for follow up for CL CaP?
GUIDELINE STATEMENT 66
PSA (even though all PSA recurrences are not associated with mets or mortality)
RP < 0.02
RT + ADT nadir PSA < 2 with T recovered (if ADT)
recommended for at least 10 years
What can be used to inform patients of individualized post-treatment prostate cancer recurrence?
GUIDELINE STATEMENT 67
Nomograms taking in to consideration:
tumor grade and stage
race
fhx
age
pathologic stage
etc
+/- genomic testing
What would you tell a patient are the benefits of PSA screening as expressed in the number of deaths averted per 1000 men from a key RCT? What study is this? What study refutes this?
ERSPC (European Randomized Study of Screening for Prostate Cancer): 1 death fewer per 1000
**RRR of CSM 21% at median f/up of 11 years
PLCO (Prostate, Lung, Colorectal, and Ovarian): NO benefit
What are FP and FN in regards to CaP screening?
FP (false positive): elevated PSA with neg bx
FN (false neg): cancer present without elevation in PSA
Potential harms associated with PSA screening?
- Over Diagnosis: ERSPC 66%, SEER 23-43%
- Hematuria/hematospermia: ERSPC 20-50%
- Fever: ERSPC 3.5-4.2%
- Psychological
- Sepsis: 4%
- Pain (pain, fever, bleeding, infection, problems urinating 30%)
Discuss possible patient factors that may trigger prostate biopsy being performed?
- PSA > 3, ERSPC
- Prostate volume
- Inflammation (no benefit of abx in asx man)
- Age (55-69)
What does the panel RECOMMEND for PSA screening > 70 years old or any man with < 10-15 year life expectancy?
GUIDELINE STATEMENT 5
NO screening
If so, increase threshold to PSA > 10 (PIVOT study)
Discontinue if PSA < 3
DDX of elevated PSA (asx)
BPH
UTI
Prostatits
Prostate cancer
Describe some key features of mpMRI prostate?
Key Points
Optimal scanning technique should utilize 3.0T surface coil; an endorectal coil may be necessary for older 1.5T scanners
T2→dark lesion concerning for cancer
DWI (diffusion weighted)→bright lesion corresponding T2 lesion
DCE (dynamic contrast enhanced imaging)→early enhancement with early washout corresponding to T2 lesion
ADC (apparent diffusion coefficient)→dark corresponding to T2 lesion
Identification and reporting of putative tumors uses anatomic and functional images.
The radiographic report should identify up to 4 suspicious lesions with each individual lesion reported and characterized using PI-RAD v2 criteria.
Stratified by PiRADS score, what is correlation to all tumor and Gl_>_7 detection?
All tumor detection:
PI-RADSv2: 2→0-22%, 3→10-16%, 4→30-77% and 5→78-89%
Gleason _>_7
PI-RADSv2: 2→5-6%, 3→0-14%, 4→21-78% and 5→75-100%
Can you use mp MRI in biopsy naïve patients?
Two randomized clinical trials (PROMIS, PIVOT, MRI-FIRST)have provided level 1 data to support use mpMRI prior to biopsy for ALL men
mpMRI-targeted prostate bx in naive patients detects more clinically significant CaP when combined with systematic biopsy (less clinically insignificant CaP, than systematic biopsy alone), but must combine systematic due to risk of missing some clinically significant cancer with targeted alone
How do FQ work? What are a/e?
Inhibit DNA gyrase
A/E include allergic reaction, tendonitis, and tendon rupture, exacerbation of muscle weakness in pts with MG
What is important for template of systematic biopsy?
Incorporation of templates that adequately sample apex, anterior apex, far-lateral region, including base and midgland (little benefit of TZ)
Size important
Describe risks of RP?
invasive, anesthesia, recovery and time off, limitation of activity post-op, risk death (<0.1%), hemorrhage (<5%), infection, positioning injury (fibular and ulnar nerves), injury to rectum (1%), bladder/bladder neck contracture (<5%), damage to obturator nerves and iliac vessels
Risks of positive margins (up to 20%), need for adjuvant tx (RT +/- ADT)
What are risks of RT for CaP?
higher risk of bladder/bowel dysfunction→acutely (50%) → LT (5%) (brachy>EBRT), no pathologic specimen, PSA is not a great marker, fatigue, impotence, incontinence (longer term)
Key element to account for when describing the start RP?
- Pre-operative abx
- (Ancef, Gent + Flagyl, Aztreonam +Flagyl, Gent+ Clinda, Aztreonam + Clinda)
- Mechanical and Chemical DVT ppx
- Positioning to pad pressure points (ulnar/fibular nerves)
- RALP→supine arm tucking
- Access Veress or Hasson (drop test, check opening pressure with gas, use visual obturator)
Describe standard steps of RALP?
- After positioning and access
- Enter space of Retzius (drop bladder)
- Isolate and ligate the DVC
- Separate bladder and prostate
- Athermal dissection of SV and Vas
- Blunt and athermal dissection of posterior plane between rectum
- Antegrade nerve sparing
- Preservation of urethral length
- Vesico-urethral anastomosis (test anastomosis)
- PLND
Describe PLND with RALP?
- A standard PLND from the external iliac vein down to the internal iliac artery (including tissue within the obturator fossa), pelvic sidewall laterally, proximally up to the bifurcation of the common iliac artery, and distally to Cooper’s ligament.
-
Definitions of extended and super extended lymph node dissection have been introduced. Their role is currently under investigation.
- Extended LND: External iliac, obturator fossa, hypogastric/internal iliacs, common iliac below the point where the ureter crosses.
- Super extended LND: Above, plus pre-sacral lymph nodes and entire common iliac below the aortic bifurcation.
Ddx of bradycardia and hypotension during RALP? Next steps?
- Cardiac events
- Air embolus
- Vagal response to pneumo
*Check for injury if port in place
*Desufflate to release intra-abdominal pressure
*Auscultate for cogwheel murmur (air embolus)
What do you do if you lose control of DVC during RALP?
- suction judiciously to keep up pneumo
- turn pneumo to 20 mmHg (if pt can tolerate)
- pack with sponge/raytec, lap → needle drivers → ligate, stitch
Describe intraoperative iatrogenic injuries during RALP and mgmt.?
- Rectal injury
- Sharp < 1.5 cm → close primarily, leave drain, advance diet slowly
- If RT/salvage → colorectal consult (diversion with colostomy)
- Thermal injury → debride injury prior to closing
- Large size → consider colostomy
- Nerve transection
- Intraoperative repair of obturator nerve (can ask for NSG-prob unavailable)
- Robotic magnification or loupes, close perineural tissue in one later interrupted 6-0 Prolene non-absorbable monofilament (tension free)
- Secondary hole (button hole) bladder
- When dissecting posterior BN off prostate
- Inspect BN for damage to UOs (can insert 5 Fr caths)
- Leave drain, cystogram before foley removal
Post RALP patient severe pain and decreased UOP, next steps? DDx?
- Examine patient, vitals, abdomen, JP output
- Labs (CBC, BMP, Trop/CKMB, EKG, JP Cr)
- Irrigate foley gently for clot
DDX:
- Cardiac event
- PE
- Hemorrhage
- Unrecognized bowel injury
- Clogged Foley
Post RALP f/up ?
Removal of foley/staples
Kegels (help recovery continence)
+/-PDE5I (penile rehab)
Repeat PSA 1 mo
What are a/e for PDE5I?
All→ flushing, nasal congestion, priapism (theoretical)
Viagra→blue/green visual changes
Cialis→muscle aches
What are options for post RALP ED?
- PDE5I
- ICI (a/e priapism, pain, curvature/scarring)
- VED (floppy, ecchymosis, pain)
- IPP (if failure non-invasive)
If 39 yo M comes in for PSA due to fear, no FHX? What do you do?
Examine patient, VS
Review prostate screening guidelines (low prevalence, no benefit of screening)
Age adjusted PSA trends:
40-49 (don’t screen): 0-2.5
50-59: 0-3.5
60-69: 0-4.5
70-79: 0-6.5
Not exhaustive, somewhat from old doctrine, but as a reference
Patient with cT2b CaP, PSA 7.8, and lower back pain, what should be considered as part of workup?
Bone Scan
What are treatment options for favorable intermediate risk CaP?
- RP + PLND
- EBRT + 4-6 mo ADT
- EBRT + Brachy with 4-6 mo ADT
- Brachy
What are potential problems when considering RP as tx option?
- Advanced age
- Previous intra-abdominal or pelvic surgery (trauma-i.e. GSW)
- Post-prostatectomy sepsis (impact tissue planes)
What are definitions for BCR after RT?
ASTRO: 3 consecutive rises in PSA
Pheonix: Nadir + 2
A/E of ADT:
- Body habitus changes→gynecomastia, testicular atrophy, loss of muscle mass, increase in fat
- Elevation of lipids and cholesterol
- Diabetes
- CVD (+/-)
- Anemia
- Fatigue (common)
- Osteoporosis
- Sexual dysfunction→decreased libido, ED
- Infertility
- Hot flashes (common)
Define types of Biochemical recurrence (BCR)
rising PSA without metastatic disease
After initial therapy OR after exhaustion of local treatment (i.e. salvage RT or salvage RALP/local ablative therapy)
RP: PSA 0.2 and confirmatory 0.2
RT: Pheonix → nadir + 2; Astro → 3 consecutive rises
Define metastatic hormone-sensitive prostate cancer
not yet treated with ADT or still responsive
absence of clinical progression, radiographic progression or rising PSA of _>_2 above nadir
can occur as recurrence after initial local therapy or de novo mets→at time of initial dx
(distinction important when deciding systemic tx)
Also volume and site important
Define castrate resistant prostate cancer:
either metastatic→
non-metastatic→PET-CT (small volume better than CT/MRI/bone scans used in past)
patient on ADT
despite castrate levels of androgens (T<50, <20→post orchiectomy), the androgen receptors (AR) remain active and continues to drive CaP progression
PSADT at least 3 values measured > 4 weeks apart or continuous rising PSA (minimal value 2), or new radiographic or clinical progression
High volume metastatic CaP vs. low volume
CHAARTED study
visceral or bone mets > 4 mets
At least one outside vertebral column and pelvis
low volume is anything less
High risk metastatic CaP
LATITUDE study
poorer prognosis
Gl_>_8, _>_3 bone lesions, measurable visceral mets
In patients with suspicion of advanced prostate cancer and no histologic diagnosis, what is the next step based on CLINICAL PRINCIPLE?
GUIDELINE STATEMENT 1
Obtain tissue diagnosis from primary tumor or metastatic site (when feasible)
CLINICAL PRINCIPLE would dictate that clinicians discuss treatment options for advanced CaP based on:
GUIDELINE STATEMENT 2
life expectancy, comorbidities, preferences, tumor characteristics, and multidisciplinary approach (uro, med onc, palliative, RT)
When diagnosing advanced prostate cancer CLINICAL PRINCIPAL states clinicians should encourage what QOL and support measures?
GUIDELINE 3
- Pain control, manage urinary sxs, a/e, and sexual sxs
- Engagement in professional and community based advocacy groups
What SHOULD clinicians advise patients with BCR about risks and follow up studies?
GUIDELINE STATEMENT 4
risks of metastatic disease
serial PSA and clinical evaluation
consider radiographic assessment based on overall PSA and PSA kinetics
High risk s/p RP: GG4/5 (Gl > 8) or PSADT < 1 year
High risk s/p RT: GG4/5 (Gl > 8) or PSADT < 18 months
*Pts that don’t meet these criteria considered low risk
Clinicians SHOULD perform what in patients with BCR who are considered high risk for clinical metastasis?
GUIDELINE STATEMENT 5
Perform periodic staging imaging: cross sectional (CT/MRI) and bone scan
GUIDELINE STATEMENT 6
Conventional studies rarely detect mets PSA _<_5
May utilize novel PET-CT (fluciclovine, choline, PMSA) as alternative (greater sensitivity)
Reminder:
High risk s/p RP: GG4/5 (Gl > 8) or PSADT < 1 year
High risk s/p RT: GG4/5 (Gl > 8) or PSADT < 18 months
*Pts that don’t meet these criteria considered low risk
In patients with BCR (after failure of local therapy) and no evidence of mets by conventional imaging, clinicians SHOULD offer:
GUIDELINE STATEMENT 7
Observation vs. clinical trial
*Jump to systemic therapy does not always yield better outcomes (balance with a/e and QOL)
GUIDELINE 8
ADT should not routinely be initiated
IF it is, intermittent (studies 8 mo treatment cycle) in lieu of continuous
In patients with mHSPC, clinicians SHOULD assess the extent of mets where and how?
GUIDELINE STATEMENT 9
bone, LN, visceral
Conventional imaging
Aggressive Cancer → D’Amico risk factors
cT3a or greater, GG 4/5, PSA >20
CT/MRI (with consideration of chest) and bone scan
Rapid progression to met dz → high path or bx Gl score, short interval to BCR, short PSADT
PET holds great promise [PSMA, fluciclovine (PSA >1)]
In newly dx mHSPC what stratification SHOULD clinicians perform? What also SHOULD be assessed to guide discussions of prognosis and further dz mgmt.?
GUIDELINE STATEMENT 10
High volume vs. Low volume
High volume → > 4 bone mets with at least one met outside spine/pelvis and/or presence of visceral mets
*CHAARTED study shows OS benefit for high volume dz of chemohormonal tx
GUIDELINE STATEMENT 11
Assess for symptoms
*bone pain with poorer 10-year survival
When initiating ADT in mHSPC, how SHOULD clinicians utilize PSA and imaging?
GUIDELINE STATEMENT 12
Baseline PSA, serial PSA at q3-6 mo. intervals after initiation of ADT
consider periodic conventional imaging
*PSA nadir (~6 -7 mo.) important in prognosis and risk stratification (PSA < 4 and < 0.2, important cutoffs regarding OS)
Imaging: esp. for poorly differentiated, ductal, neuroendocrine (often no PSA rise) → sxs → periodic imaging
In mHSPC, regardless of FHx or age, clinicians SHOULD offer the following:
GUIDELINE STATEMENT 13
genetic counseling and germline testing
GUIDELINE STATEMENT 14
ADT with either LHRH agonists or [antagonists or surgical castration]→avoid “testosterone flare”
GUIDELINE STATEMENT 15
Continued ADT in combo with androgen pathway directed tx (abiraterone + prednisone, apalutamide, enzalutamide) or chemotherapy
GUIDELINE STATEMENT 18
Do NOT offer androgen receptor pathway tx w/out ADT
What chemotherapy for mHSPC? What is pharmacologic MOA?
Docetaxel → potent inhibitor of microtubule assembly and disassembly
CHAARTED AND STAMPEDE TRIALS
Greater OS and longer median time to progression
*A/E febrile neutropenia, lethargy, asthenia, GI effects
What androgen pathway agents are used for mHSPC? What is pharmacologic MOA?
- Abiraterone Acetate (Zytiga)
→ non-steroidal irreversible inhibitor of CYP17A1 (which catalyzes conversion of C21 progesterone precursors to C19 adrenal androgens, DHEA and androstenedione)
ESSENTIALLY potent inhibition of gonadal and extragonadal androgen synthesis
1000 mg daily (250 mg x 4 at once)
Significantly longer OS and median length of radiographic PFS
A/E → elevate liver enzymes (caution liver failure), mineralocorticoid-related HTN (20%) and hypokalemia (10%)
- Apalutamide (Erleada)
→ non-steroidal anti androgen, acts as AR inhibitor that binds directly to t he ligand binding domain of AR (inhibits DNA binding)
240 mg daily
A/E: rash, seizure, GI, weight loss, arthralgia, fatigue, falls
- Enzalutamide (Xtandi)
→ novel AR signaling inhibitor, competitive for androgen binding and inhibits translocation of AR, DNA binding, and co-activator recruitment
*PFS significantly reduced + ADT (HR = 0.39)
160 mg daily
A/E: fatigue, seizures
In patients with mHSPC, low-volume mets clinicians MAY offer:
GUIDELINE STATEMENT 16
primary radiotherapy to prostate + ADT
When SHOULD clinicians offer first generation anti-androgens? What are they? What is pharmacologic MOA?
GUIDELINE STATEMENT 17
ONLY for blockage of testosterone flare
bicalutamide, flutamide, nilutamide
in combo with ADT for 2-4 weeks
MOA: competes with androgen for AR, blocking the action of androgens of adrenal and testicular origin
At what intervals should PSA and conventional imaging be used for nmCRPC?
GUIDELINE STATEMENT 19
PSA q3-6 mo. interval, and calculate PSADT at time of development of castrate resistance (PSADT < 10 mo. used to ID highest risk)
GUIDELINE STATEMENT 20
Assess for mets q6-12 mo.
*Exact interval determined by PSADT, sxs, patient/MD preference (< 10 mo.), once on ART could extend intervals to 12 mo.
In patients with nmCRPC what denotes high risk of developing mets? What SHOULD patients be offered for tx?
GUIDELINE STATEMENT 21
Apalutamide, darolutamide, enzalutamide with continued ADT
high risk patients PSADT < 10 mo
(**Lack of FDA approval of abiraterone + prednisone in men with nmCRPC–some data to support OS and PFS, but insufficient for approval)
In patients with nmCRPC AND low risk of developing mets? What SHOULD patients be offered for tx?
GUIDELINE STATEMENT 22
observation with continued ADT (PSADT > 10 mo)
GUIDELINE STATEMENT 23
Do NOT offer systemic chemotherapy or immunotherapy (only clinical trial)
In patient with newly diagnosed mCRPC, what labs, imaging, and patient specific factors should be done/reviewed? What interval of imaging ongoing?
GUIDELINE STATEMENT 24
Baseline labs → PSA, testosterone, LDH, Hgb, ALP
Review CT/MRI and bone scan → location of mets (visceral highest risk)
Disease related sxs and performance status
*Risk factors increased with elevated LDH, T <20-50, higher PSA, shorter PSADT
GUIDELINE STATEMENT 25
Conventional (CT/MRI, bone scan) at least annually or interval determined by lack of response (BCR, sxs)
In pts with mCRPC what SHOULD be done to inform prognosis and counsel regarding familial risk and targeted tx?
GUIDELINE STATEMENT 26
Germline and somatic tumor genetic testing
→ ID DNA repair deficiency mutation and microsatellite instability status
In newly dx mCRPC clinician SHOULD offer the following tx and MAY offer which tx:
GUIDELINE STATEMENT 27
continued ADT + abiraterone+ pred, docetaxel, OR enzalutamide
GUIDELINE STATEMENT 28
MAY offer sipuleucel-T in asx or minimally sxs
→ immunotherapy (IMPACT trial RRR death 22%)
→ often does not show reduction PSA or radiologic dz
GUIDELINE STATEMENT 30
In sequencing agents, consider prior tx and new tx with alternate MOA
*possibly abiraterone followed by enzalutamide (suggested in study)
What SHOULD clinicians offer to patients with sxs of bony mets from mCRPC AND without known visceral dz or LAN >3 cm?
GUIDELINE STATEMENT 29
Radium-223
→ alpha emitting radiopharm capable of inducing ds DNA breakage in cancer cells with little damage to surrounding tissues
→ not usually associated with PSA decline, must assess for occult visceral dz (CT + CXR prior to cycle 4/6 months)
In mCRPC pts who received prior docetaxel +/- abiraterone + pred OR enzalutamide, clinician MAY offer:
GUIDELINE STATEMENT 31
Cabazitaxel
3 chemotherapies FDA approved:
docetaxel, mitoxantrone (no surv. benefit), and cabazitaxel
GUIDELINE STATEMENT 32
Cabazitaxel OVER other alternative androgen pathway directed tx as third line
In patients with deleterious or suspected deleterious germ-line or somatic homologous recombination repair gene-mutated mCRPC AND prior tx with enzalutamide OR abiraterone + pred and/or taxane chemotherapy, clinician SHOULD offer:
GUIDELINE STATEMENT 33
PARP inhibitor (Lynparza)
→ leverage defects in DNA repair → cell death
OR
Platinum base chemotherapy (Carboplatin) → (if cannot use/obtain PARP inhib.)
In patients with mismatch repair deficient or microsatellite instability high mCRPC, clinicians SHOULD offer:
GUIDELINE STATEMENT 34
Pembrolizumab (anti PD-1 → Ketruda)
In regards to bone health in advanced CaP, what SHOULD physicians discuss and recommend?
GUIDELINE STATEMENT 35
Discuss risk of osteoporosis associated with ADT, assess risk of fx
GUIDELINE STATEMENT 36
Preventative tx for fx: supplemental Ca, Vit D, smoking cessation, weight bearing exercise
GUIDELINE STATEMENT 37
High risk of fx → bisphosphonates or denosumab (Prolia) (dentist-jaw)AND referral to MD who manages osteoporosis (endo, ortho, PCP)
GUIDELINE STATEMENT 38
Should rx bone-protective (denosumab-Prolia or zolendronic acid-Reclast/Zometa) agent for mCRPC with bony mets to prevent SRE
Define adjuvant RT:
ART (adjuvant) is post RP with higher risk of recurrence because of adverse pathologic features prior to recurrence (i.e. undetectable PSA)
First PSA 2-3 mo
ART usually starts 4-6 mo (after return of acceptable urinary control)
Define salvage RT:
RT to prostatic bed and surrounding tissues, including LN, in patient with PSA recurrence after sx but no evidence of mets
Some outcomes to support ART:
SWOG, EORTC, ARO
Reduction in BCR
Locoregional recurrence
Hormone tx free survival
Clinical progression
Metastatic recurrence and OS (unclear benefit–1 of 3 studies suggest yes)
What are key NNT for the SWOG, EORTC, and ARO studies in relation to ART?
BCR 4.2 (combine SWOG and EORTC)
Local recurrence 9.8
Clinical Progression 13.8
**based on NNT should be offered to all patient at high risk of recurrence
Doses of RT for SRT and ART?
65 Gy in post RP setting
RT toxicity is measured how?
Rating system 0 - 5
0 → no change in function
3 → outpt tx
4 → inpt tx
5 → death
Common Toxicity Criteria Adverse Event
When counseling a patient for RP, what SHOULD they be counseled regarding the pathologic features and additional tx?
GUIDELINE STATEMENT 1
Adverse pathologic features: + margins, SVI, EPE (recurrence >60% @ 5 y)
Advised adjuvant therapy such as RT +/- ADT may be beneficial
Adverse pathologic findings on RP, patients SHOULD be advised that RT compared to RP alone reduces what?
GUIDELINE STATEMENT 2 and 3
should inform and offer due to reduction in:
BCR, local recurrence, and clinical progression
ART on subsequent mets and OS is less clear (⅓ RCT addressed this, ⅔ did not–were not designed for that)
reduction in salvage tx and associated toxicities
PSA recurrence after RP carries what risks? What SHOULD clinicians do to monitor?
GUIDELINE STATEMENT 4
higher risk of mets or death
regular PSA monitoring
early admit of salvage tx
[early rise of PSA → more rapid dev of mets < 2 years, PSADT <10 mo, mets w/in 5 years and died approx. 5 years (2-12)]
Definition of BCR after RP:
GUIDELINE STATEMENT 5
BCR → detectable or rising PSA after sx > 0.2 with second confirmatory > 0.2
Ultrasensitive assays ( > 0.07) → lack of data (but clinician knowledge and patient specific factors)
At PSA recurrence, what MAY be considered before tx:
GUIDELINE STATEMENT 6
A re-staging evaluation
(low yield bone scan PSA <10)
MRI w/contrast (DCE) → highest and most consistent sens (>70-80%) and spec for detection of local recurrence
LN recurrence → insufficient data, possibly PET
Bones → SPECT, DWE MRI, PET???
Pts with PSA or local recurrence after RP with no evidence of distant mets SHOULD be offered which txs and counseling:
GUIDELINE STATEMENT 7
SRT
(significant reduction in local recurrent and systemic progression)
GUIDELINE STATEMENT 8
effectiveness for SRT (for PSA recurrence) is greater when given at lower levels of PSA
→ ideally < 1
GUIDELINE STATEMENT 9
+ offer ADT
→ pts s/p RP PSA > 0.2 with no distant mets
Patients should be informed of what A/E and clinical benefits for RT:
GUIDELINE STATEMENT 10
Short and Long Term urinary, bowel, and sexual
Benefits of controlling dz recurrence
Urinary incontinence (mild worsening after ART/RP or new onset)
ED (few studies, likely worsened, additional salvage tx with ADT increase osteoporosis, CVD, other issues)
Secondary malignancy (little date, confounding i.e. smoking, real risk not known)
For EBRT what is moderate and conventional fractionation:
Moderate hypofractionation: 240-340 cGy per fraction
Conventionally fractionated 180-200 cGy per fraction
Ultrahypofactionated > 500 cGy per fraction
In men with low risk prostate cancer who decline AS, which RT SHOULD be offered?
GUIDELINES STATEMENT 1A
EBRT to prosate w/ or w/o SV
Offer moderate hypofractionation
In men with intermediate risk prostate cancer RT SHOULD be offered?
GUIDELINE STATEMENT 1B
EBRT to prosate w/ or w/o SV
Offer moderate hypofractionation
In men with high risk prostate cancer RT SHOULD be offered?
GUIDELINE STATEMENT 1C
Prostate, not PLN
Offer moderate hypofractionation
Moderate hypofractionation should be offered to whom? What about f/up of studies?
GUIDELINE STATEMENT 1D
Offer regardless of patient age, comorbidity, anatomy, and urinary function
→ limited f/up beyond 5 years for most RCTs
What should men be counseled about regarding toxicities with moderate hypofractionation?
GUIDELINE STATEMENT 1E
small increased risk of acute GI toxicity
similar risk of acute and late GU and GI toxicity compared to conventional
What regimen of hypofractionated EBRT SHOULD be delivered? Is one recommended over another based on cancer or patient features?
GUIDELINE STATMENT 2A
6000 cGy delivered in 20 fractions of 300 cGy (4 weeks)
7000 cGy delivered in 28 fractions of 250 cGy
GUIDELINE STATEMENT 2B
One moderate hypofractionated regimen is not suggested over another for specific risk group
Efficacy of regimens does not appear to be impacted by age, comorbidity, anatomy, or urinary function
In men with CaP describe which men you can consider ultrahypofractionated RT?
GUIDELINE STATMENT 3A
Low-risk men who decline AS
GUIDELINE STATEMENT 3B
Intermediate-risk men (strong encouragement to participate in clinical trial or multi-institutional registry)
GUIDELINE STATEMENT 3C
High-risk men NO ultrahypofractionation outside of clinical trial or multi-institutional registry
What is ultrahypofractionated RT doses targeted to low and intermediate risk patients? What prostate size?
GUIDELINE STATEMENT 4A
3500 - 3625 cGy in 5 fractions of 700 - 725 cGy
Prostate volume < 100 cc
GUIDELINE STATMENT 4B
5 fractions at doses of 3625 c Gy and above is not suggest outside trial or registry due to late toxicity
GUIDELINE STATEMET 4C
5 fraction using consecutive daily treatments is not suggested (late urinary and rectal toxicity)
For moderately- or ultra- hypofractionated tissue constraints used in clinical trials for RT compare in terms of toxicity and QOL?
GUIDELINE STATEMENT 5A
At least 2 low-dose volume constraint points for rectum and bladder should be used, one at high-dose end (near the total dose prescribed) and one in the mid-dose range (near the midpoint of the total dose)
GUIDELINE STATEMENT 5B
Use of normal tissue constraints differing from published studies is NOT recommended
What are other key features of RT with moderate hypofractionation or ultrahypofractionation?
GUIDELINE STATEMENT 6A
Not recommended for volume and margin definitions other than those published
GUIDELINE STATEMENT 7A
IGFR is universally recommended
GUIDELINE STATEMENT 8A
Non-modulated 3-D CRT techniques are not recommended
What are some worrisome features when considering RALP?
Advanced age
Hx of intra-abdominal and pelvic sx (collateral damage for adhesions etc.)
Post biopsy prostatitis/sepsis (impact tissue planes)
What should you do for a patient with hx of CaP, severe low back pain, weakness in LE, decreased rectal tone on DRE?
Concern mets and cauda equina syndrome
NSG consult
MRI
Possible urgent surgical decompression
What is the quickest way to medically castrate a CaP patient?
Ketoconazole and Prednisone → inhibits multiple cytochrome p450 enzymes, inhibits production of glucocorticoids and mineralocorticoids, castrate in 8 h
GnRH antagonists → block pituitary receptors, no flares, castrate in days (follow LFTs)
What are AUA recs for Abx ppx in patients with previous joint replacement? What is recommended?
Must meet both criteria below:
- Increased risk of hematogenous total joint infections: 2 years after replacement, immunocompromised (inflammatory arteriopathies, drug induced, radiation), comorbidities (previous joint infections, malnourishment, hemophilia, HIV, DMII, cancer)
- Increased risk of bacteremia associated with urologic procedures: stone manipulation, transmural incision into urinary tract, endoscopic procedure of upper tract, including bowel segments, prostate biopsy, high risk of colonization (indwelling or CIC, stent, retention, hx of recurrent UTI, diversion)
Tx:
single Quinolone dose, amp (2 g) + gent (1.5 mg/kg)
How does Bactrim (TMP/SMX) work?
inhibiting folate in bacterial cells → death
a/e nausea, vomiting, rash, diarrhea, Steven’s Johnson, c. diff
How many men avoid treatment because of AS?
67%
What are predictors of positive response to SRT?
Radiation dose and modality
Slow PSADT (< 10 mo)
Low pre-radiation PSA (optimally <0.5)
Low Gleason score
Compare SRT to ART?
RFS → SRT: 47% ART: 52%
MFS → SRT: 69% ART: 70%
OS → SRT: 72% ART: 73%
*Insufficient data, little long term difference
What are the theoretical mechanisms of RT + ADT synergistically?
- Alter PSA kinetics in patients who eventually relapse
- Systemic disease control (micromets might retain sensitivity to ADT)
Why can’t you compare observational studies for ART and SRT?
- Differences in failure definition, follow up duration, RT technique, use of ADT
- SRT usually higher dose than ART
- ART with more adverse pathology
- ART studies include low risk patients w/ or /wo RT, so skews results
Patient presents with PSA 20, up from 2.3, 1 mo ago, with hx of RALP, pT3bN1M0? Labs? Imaging?
PSA, testosterone, LDH, Hgb, ALP
CT A/P, Bone Scan, F18 PET +/-
A/E of Abiraterone
Fluid retention
HTN
Hypokalemia
Liver dysfunction
(Monitor: PE (edema) BP, K+, LFTs → AST, ALT, bili q 2 weeks x 3 mo, then monthly)
The most common a/e of docetaxel?
infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia (taste), dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, fingernail changes
.
