Prostate Cancer Flashcards

1
Q

What the RECOMMENDATION for PSA screening < 40 yo?

A

GUIDELINE STATEMENT 1

Do NOT
Low prevalence of CaP, no evidence of screening benefit

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2
Q

For ages 40-54 what RECOMMENDATIONS for PSA for CaP screening?

A

GUIDELINE STATEMENT 2

Do NOT perform

*not studied sufficiently in PLCO and ERSPC trials

UNLESS shared decision making d/ higher risk:

  1. AA race
  2. Family hx of metastatic/lethal adenocarcinoma(prostate, male/female beast cancer, ovarian, pancreatic) spanning multiple generations, multiple first degree relatives at young ages
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3
Q

What does the panel RECOMMENDED for PSA screening for ages 55-69?

A

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

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4
Q

What does the panel offer and OPTION for PSA screening frequency?

A

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

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5
Q

What are the risks of prostate cancer screening?

A
  1. Psychological
  2. Hematuria
  3. Hematochezia
  4. Hematospermia
  5. Dysuria
  6. Retention
  7. Pain
  8. Infection
  9. Over-diagnosis
  10. Over treatment
  11. Transient ED
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6
Q

Describe some elements included in SDM for PSA screening for CaP?

A
  1. Putative mortality benefit of screening (overall 3% risk of dying)
  2. Description of options after abnormal PSA
  3. 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)
  4. Description of subsequent tests needed
  5. Harms of screening (additional procedures, hospitalizations, sepsis)
  6. Information about prostate gland anatomy an function
  7. CaP incident and mortality
  8. Treatment options for early and late CaP
  9. Complications of treatment options
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7
Q

Current AUA guidelines recommend which abx for prostate biopsy?

A

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)

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8
Q

List the grade groups for CaP:

A
  1. Grade Group 1: Gleason 3+3
  2. Grade Group 2: Gleason 3+4
  3. Grade Group 3: Gleason 4+3
  4. Grade Group 4: Gleason 8 (4+4, 3+5, 5+3)
  5. Grade Group 5: Gleason 9-10 (4+5, 5+4, 5+5)
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9
Q

Prostate cancer T1 staging

A

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

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10
Q

Prostate cancer T2 staging

A

T2 → prostate cancer completely inside gland

T2a → in only < 50% of one lobe

T2b → in > 50% of one lobe

T2c → cancer in both lobes

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11
Q

Prostate cancer T3 staging

A

T3 → cancer broken through capsule

T3a → broken through capsule

T3b → spread to SV

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12
Q

Prostate cancer T4 staging

A

T4 → spread to other organs nearby (rectum, bladder, levator muscles, pelvic wall)

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13
Q

CaP Risk Stratification → Very Low Risk

A

Very Low Risk must have all:

  1. PSA <10
  2. GG1 (Gl 6)
  3. T1-T2a
  4. <34% total biopsy cores positive
  5. no core >50% involved
  6. PSA density <0.15
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14
Q

CaP Risk Stratification → Low Risk

A

Low Risk must have all:

  1. PSA < 10
  2. Grade Group 1
  3. T1-T2a
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15
Q

CaP Risk Stratification → Intermediate Risk

A

Intermediate Risk:

  1. PSA 10-20 OR
  2. GG 2-3 OR
  3. T2b-c
    1. Favorable GG1 (with PSA 10 - <20) or GG2 (with PSA <10)
    2. Unfavorable: GG2 (either PSA 10 - <20) or T2b-c OR GG3 (PSA < 20)
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16
Q

CaP Risk Stratification → High Risk

A

High Risk:

  1. PSA >20 OR
  2. GG 4-5 OR
  3. _>_T3
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17
Q

At CaP diagnosis, it is a STRONG RECOMMENDATION to utilize SDM, incorporating these key elements:

A

GUIDELINE STATEMENT 1 (CLINICALLY LOCALIZED CAP)

  1. Risk category
  2. Patient values and preferences
  3. Life expectancy
  4. Pre-treatment General functional and GU sxs
  5. Expected post-treatment functional status
  6. Potential for salvage tx
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18
Q

EXPERTS suggest importance of counseling in regards to what factors at the time of CL CaP Dx?

A

GUIDELINE STATEMENT 2

Modifiable Health-Related Risk Factors

Smoking

Obesity

(Also consider frailty)

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19
Q

Clinicians are RECOMMENDED to encourage patients to meet with whom at time of dx of CaP?

A

GUIDELINE STATEMENT 3

Different prostate cancer specialists

Urology

Radiation Oncology

Med Oncology

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20
Q

Effective SDM at time of CaP dx requires clinicians to inform patients of what to make proper treatment decisions?

A

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

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21
Q

Experts suggest clinicians SHOULD inform patients to participate in what additional measure at time of CaP?

A

GUIDELINE STATEMENT 5

Clinical trials (based on eligibility and access)

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22
Q

At time of dx for low risk or very low risk CL CAP, what imaging is RECOMMENDED?

A

GUIDELINE STATEMENT 6

Clinician should NOT perform CT A/P or Bone scans

(no evidence to support need for staging)

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23
Q

Clinicians should RECOMMEND which initial tx for very-low risk CL CaP?

A

GUIDELINE STATEMENT 7

Active Surveillance

(limited or no metastatic potential, major risk serial bx → at 3-5 year intervals after confirmatory bx)

Reminder:

  1. PSA <10
  2. GG1 (Gl 6)
  3. T1-T2a
  4. <34% biopsy cores positive
  5. no core >50% involved
  6. PSA density <0.15
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24
Q

Clinicians should RECOMMEND which initial tx for low risk CL CaP?

A

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:

  1. PSA < 10
  2. Grade Group 1
  3. T1-T2a
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25
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
26
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
27
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
28
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
29
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
30
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: 1. Genomic Classifier (GC)--22 marker based on RNA → high score on bx associated with increased risk of mets 2. Genomic Prostate Score (GPS)--12 cancer genes, 20 point increase associated with SS increase HG or non-organ confined dz 3. Cell Cycle Progression (CCP)--31 cell cycle genes--increased denotes HR disease
31
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: 1. PSA 10-20 OR 2. GG 2-3 OR 3. T2b-c 1. Favorable GG1 (with PSA 10 - \<20) or GG2 (with PSA \<10) 2. **Unfavorable: GG2 (either PSA 10 - \<20) or T2b-c OR GG3 (PSA \< 20)**
32
At time of dx for intermediate risk CL CAP, what tx is RECOMMENDED?
GUIDELINE STATEMENT 16 RP or XRT+ADT
33
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: 1. PSA 10-20 OR 2. GG 2-3 OR 3. T2b-c 1. **Favorable GG1 (with PSA 10 - \<20) or GG2 (with PSA \<10)** 2. Unfavorable: GG2 (either PSA 10 - \<20) or T2b-c OR GG3 (PSA \< 20)
34
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
35
At time of dx for high risk CL CAP, what imaging is A CLINICAL PRINCIPAL?
GUIDELINE STATEMENT 22 CT/MRI and Bone Scan Reminder: 1. PSA \>20 OR 2. GG 4-5 OR 3. _\>_T3
36
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)
37
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
38
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
39
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
40
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)
41
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
42
What types of RT are RECOMMENDED for low risk CL CAP?
GUIDELINE STATEMENT 42 EBRT OR brachytherapy
43
What types of RT are RECOMMENDED for **favorable** intermediate risk CL CAP?
GUIDELINE STATEMENT 43 EBRT or brachytherapy ALONE or in combination +/- ADT Reminder: 1. PSA 10-20 OR 2. GG 2-3 OR 3. T2b-c 1. **Favorable GG1 (with PSA 10 - \<20) or GG2 (with PSA \<10)** 2. Unfavorable: GG2 (either PSA 10 - \<20) or T2b-c OR GG3 (PSA \< 20)
44
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)
45
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
46
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
47
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)
48
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
49
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)
50
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
51
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
52
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
53
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
54
Potential harms associated with PSA screening?
1. Over Diagnosis: ERSPC 66%, SEER 23-43% 2. Hematuria/hematospermia: ERSPC 20-50% 3. Fever: ERSPC 3.5-4.2% 4. Psychological 5. Sepsis: 4% 6. Pain (pain, fever, bleeding, infection, problems urinating 30%)
55
Discuss possible patient factors that may trigger prostate biopsy being performed?
1. PSA \> 3, ERSPC 2. Prostate volume 3. Inflammation (no benefit of abx in asx man) 4. Age (55-69)
56
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
57
DDX of elevated PSA (asx)
BPH UTI Prostatits Prostate cancer
58
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.
59
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%
60
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
61
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
62
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
63
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)
64
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)
65
Key element to account for when describing the start RP?
1. Pre-operative abx 1. (Ancef, Gent + Flagyl, Aztreonam +Flagyl, Gent+ Clinda, Aztreonam + Clinda) 2. Mechanical and Chemical DVT ppx 3. Positioning to pad pressure points (ulnar/fibular nerves) 4. RALP→supine arm tucking 5. Access Veress or Hasson (drop test, check opening pressure with gas, use visual obturator)
66
Describe standard steps of RALP?
1. After positioning and access 2. Enter space of Retzius (drop bladder) 3. Isolate and ligate the DVC 4. Separate bladder and prostate 5. Athermal dissection of SV and Vas 6. Blunt and athermal dissection of posterior plane between rectum 7. Antegrade nerve sparing 8. Preservation of urethral length 9. Vesico-urethral anastomosis (test anastomosis) 10. PLND
67
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.
68
Ddx of bradycardia and hypotension during RALP? Next steps?
1. Cardiac events 2. Air embolus 3. Vagal response to pneumo \*Check for injury if port in place \*Desufflate to release intra-abdominal pressure \*Auscultate for cogwheel murmur (air embolus)
69
What do you do if you lose control of DVC during RALP?
1. suction judiciously to keep up pneumo 2. turn pneumo to 20 mmHg (if pt can tolerate) 3. pack with sponge/raytec, lap → needle drivers → ligate, stitch
70
Describe intraoperative iatrogenic injuries during RALP and mgmt.?
1. Rectal injury 1. Sharp \< 1.5 cm → close primarily, leave drain, advance diet slowly 2. If RT/salvage → colorectal consult (diversion with colostomy) 3. Thermal injury → debride injury prior to closing 4. Large size → consider colostomy 2. Nerve transection 1. Intraoperative repair of obturator nerve (can ask for NSG-prob unavailable) 2. Robotic magnification or loupes, close perineural tissue in one later interrupted 6-0 Prolene non-absorbable monofilament (tension free) 3. Secondary hole (button hole) bladder 1. When dissecting posterior BN off prostate 2. Inspect BN for damage to UOs (can insert 5 Fr caths) 3. Leave drain, cystogram before foley removal
71
Post RALP patient severe pain and decreased UOP, next steps? DDx?
1. Examine patient, vitals, abdomen, JP output 2. Labs (CBC, BMP, Trop/CKMB, EKG, JP Cr) 3. Irrigate foley gently for clot DDX: 1. Cardiac event 2. PE 3. Hemorrhage 4. Unrecognized bowel injury 5. Clogged Foley
72
Post RALP f/up ?
Removal of foley/staples Kegels (help recovery continence) +/-PDE5I (penile rehab) Repeat PSA 1 mo
73
What are a/e for PDE5I?
All→ flushing, nasal congestion, priapism (theoretical) Viagra→blue/green visual changes Cialis→muscle aches
74
What are options for post RALP ED?
1. PDE5I 2. ICI (a/e priapism, pain, curvature/scarring) 3. VED (floppy, ecchymosis, pain) 4. IPP (if failure non-invasive)
75
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)
76
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
77
Patient with cT2b CaP, PSA 7.8, and lower back pain, what should be considered as part of workup?
Bone Scan
78
What are treatment options for favorable intermediate risk CaP?
1. RP + PLND 2. EBRT + 4-6 mo ADT 3. EBRT + Brachy with 4-6 mo ADT 4. Brachy
79
What are potential problems when considering RP as tx option?
1. Advanced age 2. Previous intra-abdominal or pelvic surgery (trauma-i.e. GSW) 3. Post-prostatectomy sepsis (impact tissue planes)
80
What are definitions for BCR after RT?
ASTRO: 3 consecutive rises in PSA Pheonix: Nadir + 2
81
A/E of ADT:
1. Body habitus changes→gynecomastia, testicular atrophy, loss of muscle mass, increase in fat 2. Elevation of lipids and cholesterol 3. Diabetes 4. CVD (+/-) 5. Anemia 6. Fatigue (common) 7. Osteoporosis 8. Sexual dysfunction→decreased libido, ED 9. Infertility 10. Hot flashes (common)
82
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
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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
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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
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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
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High risk metastatic CaP
LATITUDE study poorer prognosis Gl_\>_8, _\>_3 bone lesions, measurable visceral mets
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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)
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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)
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When diagnosing advanced prostate cancer CLINICAL PRINCIPAL states clinicians should encourage what QOL and support measures?
GUIDELINE 3 1. Pain control, manage urinary sxs, a/e, and sexual sxs 2. Engagement in professional and community based advocacy groups
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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
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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
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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
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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)]
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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
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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
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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
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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
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What androgen pathway agents are used for mHSPC? What is pharmacologic MOA?
1. 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%) 2. 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 3. 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
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In patients with mHSPC, low-volume mets clinicians MAY offer:
GUIDELINE STATEMENT 16 primary radiotherapy to prostate + ADT
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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
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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.
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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)
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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)
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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)
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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
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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)
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What SHOULD clinicians offer to patients with **sxs of bony met**s 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)
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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
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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.)
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In patients with mismatch repair deficient or microsatellite instability high mCRPC, clinicians SHOULD offer:
GUIDELINE STATEMENT 34 Pembrolizumab (anti PD-1 → Ketruda)
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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
112
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)
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Define salvage RT:
RT to prostatic bed and surrounding tissues, including LN, in patient with PSA recurrence after sx but no evidence of mets
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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)
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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
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Doses of RT for SRT and ART?
65 Gy in post RP setting
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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
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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
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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
120
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)]
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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)
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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???
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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
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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)
125
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
126
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
127
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
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In men with high risk prostate cancer RT SHOULD be _offered_?
GUIDELINE STATEMENT 1C Prostate, _not_ PLN Offer moderate hypofractionation
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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
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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
131
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
132
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
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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)
134
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
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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
136
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)
137
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
138
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)
139
What are AUA recs for Abx ppx in patients with previous joint replacement? What is recommended?
Must meet **_both_** criteria below: 1. **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) 2. **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)
140
How does Bactrim (TMP/SMX) work?
inhibiting folate in bacterial cells → death a/e nausea, vomiting, rash, diarrhea, Steven's Johnson, c. diff
141
How many men avoid treatment because of AS?
67%
142
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
143
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
144
What are the theoretical mechanisms of RT + ADT synergistically?
1. Alter PSA kinetics in patients who eventually relapse 2. Systemic disease control (micromets might retain sensitivity to ADT)
145
Why can't you compare observational studies for ART and SRT?
1. Differences in failure definition, follow up duration, RT technique, use of ADT 2. SRT usually higher dose than ART 3. ART with more adverse pathology 4. ART studies include low risk patients w/ or /wo RT, so skews results
146
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 +/-
147
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)
148
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
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