Prostate Cancer Staging Registrars 11.05.2018 [Read-Only] · 10/30/2018 5 Very healthy 63 year old...
Transcript of Prostate Cancer Staging Registrars 11.05.2018 [Read-Only] · 10/30/2018 5 Very healthy 63 year old...
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Martha K. Terris, MDWitherington Distinguished Professor and Chair
Medical College of Georgia UrologyNovember 5, 2018
Elevated PSA and/or nodule on digital rectal examination
Prostate biopsies If initial biopsy shows
no cancer, a variety of other tests may be performed
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3T Multiparametric MRI of the Prostate ◦ Identifies lesions in patients with negative biopsy
and persistent concern for cancer◦ Use as an initial evaluation is controversial◦ Biopsies directed at MRI lesions do not replace
random systematic biopsies
Blood◦ 4Kscore Measures kallikrein proteins: total PSA, free PSA, intact
PSA, and human kallikrein related peptidase 2 to assess a patient’s risk of having a Gleason score ≥ 7 on prostate biopsy.
◦ Prostate Health Index (phi) score includes PSA, free PSA, and proenzyme PSA (proPSA) to
estimate probability of cancer on biopsy
Urine◦ Progensa® (Gen-Probe, San Diego, CA) prostate
cancer antigen-3 (PCA3) urine assay Following a DRE, PCA3 score is calculated from a
patient’s urine to estimate the risk for prostate cancer on a subsequent biopsy.
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Biopsy Tissue◦ ConfirmMDx Uses the methylation status of three biomarkers
(GSTP1, RASSF1, and APC) from negative prostate biopsy tissue to help determine the chance of prostate cancer on a subsequent biopsy.
Low Risk◦ PSA level <10 ng/mL◦ Biopsy Gleason score of ≤6, ◦ Clinical stage of ≤T2a
Intermediate Risk ◦ PSA level of 10.1 to 20 ng/mL◦ Gleason score of 7◦ and/or a clinical stage of T2b
High Risk ◦ PSA level >20 ng/mL, ◦ Gleason score of ≥8, ◦ and/or a clinical stage of T2c-3a
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Organization Low Risk Intermediate Risk
High Risk
AUA, EAU, D’Amico
<T2a, PSA<10, and GS<6
T2b and/or PSA >10-20 and/or
GS=7
>T2c or PSA>20 or GS 8-10
GUROC, NICE <T2a, PSA<10, and GS<6
T1-T2 and/or PSA <20 and/or GS<7
>T3a or PSA>20 or GS 8-10
CAPSURE <T2a, PSA<10, and GS<6
T2b and/or PSA >10-20 and/or
GS=7
>T3a or PSA>20 or GS 8-10
Very High T3b-4NCCN <T2a, PSA<10,
and GS<6Very Low: <3cores
+ <50%
T2b or T2c and/or PSA >10-20 and/or GS=7
T3a or PSA>20 or GS 8-10
Very High T3b-4
ESMO <T2a, PSA<10, and GS<6
Any between Lowand High
>T3a or PSA>20 or GS 8-10
AUA=American Urological Association, EAU=European Association of Urology, D’Amico=Harvard, GUROC=GU Radiation Oncologist of Canada, NICE=National Institutes of Health and Clinical Excellence, Capsure=UCSF, ESMO=European Society of Medical Oncology
Oncotype Dx/genomic prostate score (GPS) ◦ Consists of 12 cancer-related genes and 5 reference
genes to evaluate cancer aggressiveness. Prolaris Score◦ Measures RNA expression of 31 genes involved in cell
cycle progression compared to 15 house keeping genes to quantify prostate cancer cellular aggression.
ProMark◦ Proteomic prognostic test that incorporates eight
biomarkers from a prostate biopsy sample to predict an individual’s risk of favorable or nonfavorable/aggressive prostate cancer.
Considered Experimental
Low Risk◦ No Staging Studies necessary◦ If choosing active surveillance may have serial MRI
and/or biopsies Intermediate Risk◦ Abdominal/Pelvic imaging (CT or MRI)◦ Bone scan if T2 and PSA >10
High Risk◦ Abdominal/Pelvic imaging (CT or MRI)◦ Bone scan if T2 and PSA >10
*NCCN Guidelines
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Very healthy 63 year old African American gentleman
Prostate Cancer on TRUS bx for elevated PSA 4.3 GS 4+4 in 7/15 cores in 2008
Treated with Brachytherapy (age 54) PSA nadir at <0.01 and was undetectable
until 2014 when PSA was found to be 0.2 Repeat PSA in 2/2017 was 4.87 and 3/2017
was 6.37.
ROS: negative PMH: prostate cancer, hypertension,
hyperlipidemia PSH: rotator cuff repair, brachytherapy Med: amlodipine, aspirin, lipitor, FH: no hx of PCa SH: non-smoker, social drinker
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IMPRESSION 1. Brachytherapy seeds identified within the
prostate gland. The prostate gland is within normal limits of size.
2. A 1.2 x 1.6 cm intermediate density structure is identified adjacent to right external iliac vein, which is highly concerning for pathologically enlarged right pelvic lymph node (i.e. nodal metastatic disease).
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Patient underwent repeat Ultrasound guided prostate biopsy
Pathology Report: Benign prostatic tissue showing treatment effect in all cores
He was advised by his urologist that Lupron was next step but was opposed to hormone treatment at this point
He presented to MCG for a 2nd opinion AXUMIN PET/CT
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Intensely increased activity in a conglomerate right external iliac lymph node group 1.3 cm short axis x 2.4 cm craniocaudal
Numerous brachytherapy seeds throughout the prostate gland. No abnormal focal uptake.
IMPRESSION: Intense regional right external iliac tumor
lymphadenopathy No other significant active lymphadenopathy or
distant metastasis
F-18 fluciclovine (AXUMIN) PET/CT
F-18 fluciclovine (AXUMIN) PET/CT
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30-40% biochemical recurrence rate after RP and 36-50% for brachytherapy within 10 years
Management Options:◦ Androgen deprivation therapy- standard Unfavorable side effect profile Progression to castration-resistant disease Significant toxicity at long term Continuous vs Intermittent◦ Salvage radiation therapy◦ Salvage ablation procedures◦ Salvage lymphadenectomy
More favorable outcome than those with metsto bone or other visceral organs
Long-term follow-up studies: good cancer-specific survival of patients with limited node-positive disease after RP ◦ Even without ADT
Removal of node may have beneficial impact on cancer progression
Tilki et al. J Urol. 2015; 193:484-490.Karnes et al. J Urol. 2015; 193:111-116.Suardi et al. Eur Urol. 2015 67:299-309.Winter et al. BMC Urol. 2015; 15:10.
Rigatti et al. 2011
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Salvage PLND after primary treatment ◦ Prolong recurrence-free survival◦ Delay systemic therapies
Efficient and precise imaging for identification of suspicious LNs would optimize salvage
Traditional CT and MRI – low sensitivity Tilki et al. J Urol. 2015; 193:484-490.Karnes et al. J Urol. 2015; 193:111-116.Suardi et al. Eur Urol. 2015 67:299-309.Winter et al. BMC Urol. 2015; 15:10.
PET/CT Scan◦ 18-fluorodeoxyglucose ◦ 11C-choline ◦ 18F-fluoroethylcholine◦ 11C-acetate ◦ Sensitivity 58% ; Specificity 69% ◦ Small (>5mm) LN metastasis◦ Limitations: 20 min t ½ ◦ Requires on-site cyclotron
Jadvar H. J Nuc Med.2011;52(1):81-89. Almeida et al. Am J Nucl Med Mol Imaging. 2017;7:1-11.
PET/CT ◦ 18F-fluciclovine (AXUMIN) - amino acid
transporter analogue Sensitivity 58% and Specificity 81% 109.7 min t ½◦ 68Ga-PSMA - transmembrane protein Prostate-specific membrane antigen (PSMA) 55% detection PSA 0.2-0.5 ng/ml 76% detection PSA 0.5-1.0 ng/ml
Pultrone et al. J Urol. 197, 4S, 2017. Maurer et al. J Urol. 197, 4S, 2017. Maurer et al. Nature Rev Urol 13, 226-235. 2016
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Diffusion-weighted MRI combined with ultra-small particles of iron oxide (USPIO) ◦ high sensitivity between benign and malignant lymph
nodes even in normal sized nodes.◦ Identified intraoperatively with hand-held magnetometer◦ Intraprostatic injection limits use in salvage setting.
Winter et al. Ann. Surg. Oncol. 2014; 21: 4390–6. Harisinghani et al. N. Engl. J. Med. 2003; 348: 2491–9.
99mTc-labeled colloids ◦ Albumin◦ Sulphur◦ Phytate◦ Require intraoperative gamma camera
Hybrid ICG and 99m Tc-nanocolloid◦ Intraoperative imaging without gamma camera
All require injection into primary tumor
Buckle et al. J. Nucl. Med. 2012;53:1026–33.
Near-infrared (NIR) intraoperative molecular imaging with indocyanine green (ICG) ◦ Intraoperative, intraprostatic injection of ICG◦ Complexity of lymphatic drainage◦ U Penn: 5 mg/kg IV ICG one day prior to node dissection
Xia et al. Urology. 2017. 106 , 133 - 138
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Future imaging with prostate-specific fluorescent compounds◦ Anti-Prostate-Specific Membrane Antigen (PSMA)
antibody (J591) linked to ICG◦ YC-27, a near-infrared-emitting fluorophore
targeted to PSMA◦ Antibody fragment (cys-diabody, cDb) against
prostate stem cell antigen (PSCA) conjugated to far-red fluorophore, Cy5
Nakajima et al. Bioconjug Chem. 2011 22:1700-5.Neuman et al. Clin Cancer Res. 2015 21:771-80.Son et al. Clin Cancer Res. 2016 22:1403-12.
Experimental treatment option for PCapatients with nodal recurrence localized on PET/CT after primary treatment failure ◦ Lack of current guidelines
Two main aims: ◦ Delay further cancer recurrence◦ Postpone use of systemic treatments
Suardi et al. Eur Urol. 2015 67:299-309.Winter et al. BMC Urol. 2015; 15:10.
To maximize oncological outcomes, avoid unnecessary morbidity [1,3]
Ideal candidate: [3,5,6]
◦ Young patients ◦ Path stage pT2◦ Gleason score ≤ 7◦ PSA < 4 ng/ml ◦ Castration-sensitive disease◦ Low LN burden limited to pelvis
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Abdollah et al. 2015
50-80% of patients achieve complete BR after SLND (defined as PSA < 0.2 ng/mL)
Significant predictor of cancer progression◦ Rigatti et al: Mean time to clinical progression Persistently elevated PSA: 28.8mo Complete BR: 64.8mo
Predictors of BR:◦ PSA <4 ng/ml◦ RP to BCR time <24mo◦ Node-negative at RP
Most invariably progress to biochemical recurrence after SLND, despite initial BR [3]
◦ Definition: PSA> 0.2 ng/ml and rising ◦ Median 18mo
9-31% BCR-free survival rate at 5 yrs◦ Suardi et al: 23% at 8 yrs
Winter et al: 3/13 complete remission (PSA<0.01) for 7 yrs◦ Potential for “cure”
Suardi et al. Eur Urol. 2015 67:299-309.Winter et al. BMC Urol. 2015; 15:10.
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Positive PET/CT after SLND + rising PSA 35%-50% CR-free survival rate at 5 yrs [3,6,7]
◦ Suardi et al: 38% CR-free survival at 8 yrs Pre-op predictors of CR: ◦ PSA >4 ng/ml at SLND [1,3]
◦ Retroperitoneal uptake at PET/CT scan Post-op predictors of CR: ◦ Pathologic nodes in retroperitoneum◦ Higher # of positive nodes◦ Incomplete PSA response to SLND
• Most reported complications were mild• No post-op mortality has been reported
Suardi et al. Eur Urol. 2015 67:299-309.
Constraints on sensitivity of current imaging techniques to detect LN recurrence
No literature currently on SLND s/p brachytherapy specifically
Studies: retrospective, small sample sizes, heterogeneous population, no controls ◦ Current randomized prospective trial ongoing Salvage Treatment or Active Clinical Surveillance for
Oligometastatic Prostate Cancer: a Randomized Phase II Trial (NCT01558427)
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A) LYMPH NODES, RIGHT PELVIC (DISSECTION):-Metastatic prostatic adenocarcinoma (2.6cm) involving one of ten lymph nodes (1/10)
B) LYMPH NODES, LEFT PELVIC (DISSECTION):-Five lymph nodes, negative for malignancy (0/5)
Tolerated procedure without complication Good biochemical response to SLND◦ Pre-op PSA: 6.37◦ 1 month post-op PSA: 0.32◦ 2 months post-op PSA: 0.04◦ 3 months post-op PSA: 0.03◦ 6 months post-op PSA: 0.02◦ 9 months post-op PSA: 0.02
New imaging techniques help localize disease recurrence after primary prostate cancer treatment.
More exact staging in recurrence increases the opportunities for directed treatment and prolonged results to salvage therapy
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