Chapter 66 Intermediate and High Risk Prostate Cancer Flashcards
D’Amico et al. Intermediate Risk criteria for prostate cancer
T2b or T2c
PSA 10-20ng/mL
GS 7
D’Amico et al. High Risk criteria for prostate cancer
T3a
PSA > 20ng/mL
GS 8-10
D’Amico et al. Locally advanced prostate cancer criteria
T3b or T4
D’Amico et al. reported percentage of positive biopsy core(PPC) as independant prognostic factor. Mention PPC with similar outcome as Low risk and High risk prostate cancer
50% PPC has similar outcome to high risk
In Radical Prostatectomy, High PPC is associated with what adverse pathological features?
ECE Seminal vesicle invasion Positive surgical margin Positive Lymphovascular invasion Positive Perineural invasion Positive pelvic lymph node involvement
Recent meta-analysis of 4 RTOG trials, what factor was associated with reduced PCSM(Prostate Cancer Specific Mortality) and metastasis?
Older age >70 years
Describe target volume for prostate cancer
Prostate
Seminal vesicles
Obturator nodes
Proximal internal and external iliac nodes
Occasionally Common iliac, Para arotic, and even peri rectal nodes are included
Describe conventional portal design for prostate cancer
4 fields
AP-PA
Superior L5-S1
Inferior 2 cm distal to membranous urethra
Lateral 1.5-2 cm lateral to pelvic brim
Opposed Lateral
Anterior anterior most aspect of pubic symphysis
Posterior S2-3 interspace
Wang Chesebro et al. Conventional 4 fields vs IMRT, state the coverage difference in terms of target volume and normal tissue sparing in prostate cancer
Conventional plan 70.3% vs IMRT 96.2% (dose coverage of 45Gy)
95% prescribed dose received by rectum and bladder, IMRT reduced 23% and 80% respectively.
Lawton et al. What is the proposed dose constraints for rectum, bladder, femoral head, small bowel during prostate treatment
Rectum V50Gy
Chen et al. Isocenter shift of 5 or 10 mm in superior direction could reduce by how much percentage of nodal target coverage?
11% and 26% respectively
Shariat et al. Studied RT-PCR/hk2(Reverse Transcriptase-Polymerase Chain Reaction/human glandular kallikrein 2) mRNA expression in histologically normal pelvic nodes in pT3N0 prostate cancer. What were the finding of occult lymph nodes involvement?
20% and 40% had occult positive and equivocal results of pelvic lymph nodes
Bader et al. What percentage of internal iliac lymph nodes were positive in limited pelvic nodal dissection in prostate cancer?
58% with positive lymph node disease
Heidenreich et al. What was the reported incidence of lymph nodes involvement between standard and extended pelvic lymphadenectomy in prostate cancer?
26% in extended vs 12% in standard
Wawroschek et al. found about a third of sentinel lymph nodes outside the limited node dissection in prostate cancer. What are those regions?
Presacral
Hypogastric
Pararectal
What is the accuracy of Roach et al formula for predicting nodal involvement in prostate cancer?
80%
In prostate cancer, recommended cutoff of >=15% to decide whether to treat pelvic nodes led to about a third with nodal involvement.Abdollah et al. what was the recommended cutoff to be lowered?
6%
RTOG-9413 (Landmark trial for prostate cancer). What are the arms studied and which one has better outcome and worst toxicities?
PORT(Prostate Only RT)
WPRT followed by PORT: late G3-5 GI toxicity seen
4 mths of neoadjuvant and concurrent hormones+WPRT : significantly better outcome(59.6%) of 4-year progression free survival than other arms
PORT+4 mths of adjuvant harmones
WPRT+4 mths of adjuvant harmones: updated RTOG-9413 has significantly greater incidence of G3-5 GI toxicities than other arms
To address controversies of WPRT in prostate cancer, RTOG-0924 identified subset of patient from RTOG 9413 who benefited from WPRT. What were criteria incorporated?
Estimated nodal risk of atleast 15%
GS 7-10 and T1c-T2b and PSA 50% biopsies) and PSA 20ng/mL
RTOG 0924 what is treatment recommendation in favor to WPRT in prostate cancer?
WPRT 45Gy(3DCRt/IMRT)
PORT 34.2Gy boost(IMRT) to complete 79.2Gy
Also permitted for boost
LDR brachy 110Gy I-125
100Gy Palladium-103
HDR brachy 15Gy/1 fnx Iridium-192
When is brachytherapy preferred after pelvic RT in prostate cancer?
1-2 weeks after
University of California-San Francisco(UCSF) treatment recommendation for low risk prostate cancer?
PORT
No hormonal therapy
University of California-San Francisco(UCSF) treatment recommendation for favorable intermediate risk prostate cancer?
PORT
Neoadjuvant(2 mths) + concurrent ADT
University of California-San Francisco(UCSF) treatment recommendation for unfavorable intermediate risk prostate cancer?
WPRT
Neoadjuvant(2 mth) + concurrent ADT
+_ adjuvant ADT(2 mth)
University of California-San Francisco(UCSF) treatment recommendation for high risk prostate cancer?
WPRT
Neoadjuvant (2 mth) + concurrent + adjuvant (24-36 mth) ADT
University of California-San Francisco(UCSF)
Describe preparation of rectum and bladder during CT simulation in prostate cancer.
Rectum should be emptied with enema prior to simulation
Full bladder during simulation and treatment
Describe the IMRT technique used for prostate cancer.
7-field isocenter if technique with 18-MV photons.
University of California-San Francisco(UCSF)
Describe definitive EBRT dose in prostate cancer
1st phase 45-54 Gy 1.8Gy/fnx in 25-30 fnx to pelvic nodes, seminal vesicle and prostate PTV
2nd phase 19.8 Gy 1.8Gy/fnx in 11 fnx cone-down boost to prostate PTV
Total of 73.8Gy
Max dose approx 82-84Gy
University of California-San Francisco(UCSF)
Describe the dose prescribed in pelvic RT followed by brachy boost.
45Gy 1.8Gy/fnx in 25 fnxs to nodes, seminal vesicles and prostate PTV
University of California-San Francisco(UCSF)
Describe the dose prescription for post operative patients in prostate cancer
45Gy 1.8Gy/fnx in 25 fnxs to nodes 50Gy 2Gy/fnx in 25 fnx to tumor bed PTV 16.2Gy 1.8Gy/fnx to prostate bed Total 66.2Gy Max dose 78Gy
Name the study which showed dose escalation still beneficial with harmones
MRC RT01
RTOG 0815 is ongoing trial
What are advantages of HDR brachytherapy over LDR brachytherapy in prostate cancer?
Flexibility in source positioning
Accurate source positioning
Immobilized target
Stable geometry
Adaption of dose to target and healthy organs
Target volume dose optimization
High quality planning and dose distribution
No radiation exposition to health worker or public
No source preparation needed
Reduced cost
More effective prostate cancer cell kill
What are disadvantages of HDR brachytherapy over LDR brachytherapy in prostate cancer?
Dose rate is higher needs fractionated needs more workload
Indications for EBRT and brachytherapy boost in intermediate and high risk prostate cancer
Young patient
High volume disease
Which patients are not eligible for brachytherapy boost in prostate cancer?
Large prostate >60cc
Prior TURP
Significant urinary symptoms
Describe Guix et al.(Prostate cancer)
Prospective randomized trial Intermediate and high risk EBRT only(76Gy) vs EBRT(46Gy)+Brachy(192Ir HDR, 8Gy/fx, 2 fx) 5 year PSA relapse free survival EBRT only intermediate(90%) high(89%) Combined intermediate(97%) high(96%) No G3-4 GI and GU toxicities
Describe RTOG 0321 phase II trial in prostate cancer
Designed to estimate G3 late GU and GI toxicities HDR brachy(19Gy in 2 fnx) and EBRT(45Gy in 25 fx) Intermediate and high risk At 18 mths G3-5 GU and GI toxicities only 2.56%
Describe ABS(American Brachytherapy Society) recommendation for LDR brachy in prostate cancer
Iodine-125 : 100-110Gy
Palladium-103 : 80-90Gy
Cesium-131 : 85Gy
What is the ideal period of LDR brachytherapy after EBRT in prostate cancer?
2-4 weeks
What is recommended EBRT in prostate cancer?
45-50.4Gy in 1.8-2Gy/fnx
What are the biological basis for combining androgen suppression therapy and radiotherapy?
- Increased overall cell kill
2. Improved outcome by diminished growth velocity in surviving prostate cancer cells after treatment.
Name 5 clinical trials in favor of Androgen Suppression Therapy(AST) in high risk prostate cancer
EORTC-22863 RTOG-8531 RTOG-8610 Quebec L-101 Granfors et al.
What was the conclusion of EORTC-22863 study in favor of AST in high risk prostate cancer?
AST reduced risk of death by 40% and improved 10-year overall survival from 40% to 58%
What was the conclusion of Quebec L-101 study in favor of AST in high risk prostate cancer?
AST had significantly improved 7-year PSA control rates better than control arm
What was the conclusion of Granfors et al. in favor of Orchidectomy in high risk prostate cancer?
Orchidectomy had 10 year prostate cancer survival and overall survival
Name 2 clinical trials in favor of AST in intermediate risk prostate cancer
BWH(Brigham and Women’s Hospital)
RTOG-9408
What is the conclusion of RTOG-9408 in favor of AST in intermediate risk prostate cancer?
10-year OS, PCSM, PSA failure, distant metastasis were significantly in favor of AST arm.
Describe RTOG-0815 in favorable intermediate risk prostate cancer(ongoing!!)
Phase III multicenter trial
6 months of androgen blockade with
-dose escalated RT with 3D-CRT or IMRT(79.2Gy)
-combined LDR(110Gy with 125I or 100Gy with 103Pd) brachy boost with 3D CRT or IMRT(45Gy to prostate and seminal vesicles)
-combined HDR(2 fraction of 10.5Gy per fnx) with 3DCRT or IMRT(45Gy to prostate and seminal vesicle)
What are toxicities of AST in prostate cancer?
Fatigue Weight gain Osteoporosis Depression Decreased cognitive function Erectile dysfunction Loss of libido Gynecomastia Anemia Decreased HDL Insulin resistance Hot flashes
According to SEER and Medicare data(50,613 prostate cancer men), what was the percentage of increased risk of fractures in addition of AST?
From 12.6% to 19.4% fracture
From 2.37% to 5.19% hospitalization because of fracture
Saigal et at. What was the percentage increase of cardiovascular morbidity in addition to AST in prostate cancer?
20%
Pickles et at. What is the overall median time for testosterone recovery to noncastrate level after adjuvant AST level and RT?
10 months
What was the conclusion of RTOG 9413 in favor of optimal timing of AST in prostate cancer?
4 year PFS was significantly improved in the arm that received WPRT and neoadjuvant AST as compared with other arms(60% vs 44-50%)
Controversies in updated RTOG 9413 in the role of elective pelvic nodal irradiation, which study is evaluating currently the role of WPRT with dose escalation with atleast 2 mths of neoadjuvant harmones?
RTOG 0924
Name 3 published randomized trials evaluating optimal duration of neoadjuvant harmonal therapy in prostate cancer
Canadian Urologic Oncology Group(CUOG)
TROG-96.01
Irish clinical oncology research group
Name the trial which showed advantage over longer duration neoadjuvant AST in prostate cancer
TROG-96.01
Describe RTOG 9910 in intermediate risk prostate cancer evaluating optimal duration of neoadjuvant AST
Compares 8 and 28 weeks of AST
What is the comparison of EORTC 22961 trial in favor of adjuvant AST?
Compared 6 months with 36 months of adjuvant AST
What is the general principle of use of AST in prostate cancer?
Intermediate risk prostate cancer - Short term AST(3-4 months neoadjuvant and concurrent) appears sufficient
High risk prostate cancer - long term >=2 years adjuvant AST appears to improve outcomes
What are the 5 landmark trials that studied AST and mandated pelvic RT?
What are their common characteristics?
4 RTOG
1 EORTC 22863
Median PSA > 20ng/mL
20-30% GS 8-10
Estimated occult pelvic nodal involvement (Roach Formula) 20%
What is Phoenix definition of PSA relapse after RT in prostate cancer?
Rise of 2ng/mL or more above the absolute PSA nadir.
Phoenix definition of PSA relapse is applicable to which patients in prostate cancer?
Patients treated with EBRT with or without short term hormonal therapy
What is the sensitivity and specificity of Phoenix definition?
64% and 78%
What are the predictive factors associated with increased risk of PSA recurrence and local recurrence?
Positive surgical margins(PSM)
Extra capsular extension(ECE)
Pound et al. what are the predictive factors for metastatic prostate cancer?
PSA recurrence
D’Amico et al. What are the prognostic factors associated with postoperative PSA-DT >=12 months or no PSA failure in prostate cancer?
Preoperative PSA
D’Amico et al. What are the prognostic factors associated with postoperative PSA-DT
GS 7-10
Preoperative PSA velocity > 2 ng/mL per year
D’Amico et al. Low Risk criteria for prostate cancer
T1c-T2a
PSA