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Dr Sasikumar Sambasivam 
DNB Resident 
Dept. of Radiation Oncology
Locally advanced disease 
include clinical stages T3 ,T4 
and bulky T2 c tumors. 
Options : ADT, RT, Surgery
Reducing intracellular concentrations of dihydrotestosterone through 
the use of androgen deprivation can induce apoptotic...
RTOG 83-07 (megestrol and diethylstilbestrol with RT in a phase II 
randomized study) --- Both the megestrol and DES in ad...
RTOG study 85-19, which utilized these agents for patients with locally 
advanced disease, found them to be well tolerated...
TAS= Flutamide 250 mg tds Goserelin monthly x 4 m
RTOG 92-02 
OS benefit was observed in patients with 
Gleason score 8 to 10 
(Along with RT)
Hot flashes(50-80 %), sexual dysfunction (universal), gynaco mastia (20%) 
and decreased libido(universal) owing to the de...
? Life threatening complications 
RTOG 85-31 and 86-10, EORTC did not report any such events in both 
the arms 
EORTC 2296...
But LHRHs donot appear to cause these met changes 
Caution in patients with obesity and pre existing CVS diseases 
Most im...
Antiandrogens : 
Bicalutamide 50 mg P/o 
Flutamide 250 mg P/o 
Nilutamide 300 mg d1-d28 f/b 150 mg as maint. 
Abiraterone ...
Treatment volumes for locally advanced prostate cancer have included 
the prostate and seminal vesicles plus a margin alon...
RTOG 94-13 
1323 patients , randomized into three groups 
WPRT versus prostate-only EBRT (PORT) and neoadjuvant 4 months 
...
Showed an unexpected interaction between the timing of the total 
androgen suppression and the extent of the EBRT field. 
...
? benefit was solely due to ADT and not RT 
SPCG-7 & SFUO-3 (Phase III RCTs) 
875 patients (Scandinavian) 
TAS for 3 month...
External beam RT 
Positioning : RCT : In the supine position, prostate movements during 
normal breathing were less than 1...
Primary Therapy : 
Clinical Target Volume : 
Pretherapy tumour related factors 
Extra prostatic extension , Seminal Vesicl...
Planning Target Volume: 
Setup errors, organ movements , bladder and bowel volumes leading to target miss 
Monitoring can ...
2 D planning : 
(1) superior: L5-S1 interspace; 
(2) inferior: bottom of ischial tuberosities; 
(3) lateral: 2 cm lateral ...
Prostate 
and 
Seminal 
Vesicles
Contouring 
of Prostate 
and Seminal 
Vesicles
Contouring of 
Prostate and 
Seminal 
Vesicles 
Contnd..
Pelvic LNs
Contouring 
of Pelvic 
nodes
Contouring 
of Pelvic 
nodes 
Contind…
3 D CRT or IMRT ( Preferred) ; IGRT in case if Dose prescription > 78 Gy 
Doses upto 81 Gy provide improved Biochemical co...
Dose Constraints Definitive Therapy ( MSKCC; 81 Gy)
Adverse pathological / lab features : 
Positive margins 
Seminal vesicle invasion 
ECE 
Detectable PSA 
pT3 disease 
Gleas...
Adjuvant 
RT / 
Salvage RT
Adjuvant 
RT / 
Salvage RT
Adjuvant 
RT / 
Salvage RT
Indicated in adverse path features ; detectable PSA with no evidence of 
disseminated disease 
Usually given within 1 year...
Dose Constraints : OARs
RP + PLND 
No fixation 
If adverse features are + ------ RT / Observation 
LN + ------- ADT / observation / ADT + Pelvic R...
The T half of PSA is 3.1 days 
PSA should be undetectable 4 weeks or more after RP 
‘PSA doubling time’ expressed as the v...
Further RTOG –ASTRO phoenix consensus defined 
Biochemical failure as 
After EBRT with or without HT : PSA rise by 2 ng/ml...
Locally Advanced Carcinoma Prostate
Locally Advanced Carcinoma Prostate
Locally Advanced Carcinoma Prostate
Locally Advanced Carcinoma Prostate
Locally Advanced Carcinoma Prostate
Locally Advanced Carcinoma Prostate
Locally Advanced Carcinoma Prostate
Locally Advanced Carcinoma Prostate
Locally Advanced Carcinoma Prostate
Locally Advanced Carcinoma Prostate
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Locally Advanced Carcinoma Prostate

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Locally advanced Ca prostate
Courtesy : NCCN , Perez, Gunderson and Tepper
Brief outline on management
ADT, Radiotherapy, Surgery indications and Standard of care

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Locally Advanced Carcinoma Prostate

  1. 1. Dr Sasikumar Sambasivam DNB Resident Dept. of Radiation Oncology
  2. 2. Locally advanced disease include clinical stages T3 ,T4 and bulky T2 c tumors. Options : ADT, RT, Surgery
  3. 3. Reducing intracellular concentrations of dihydrotestosterone through the use of androgen deprivation can induce apoptotic regression of androgen-responsive prostate cancers Could help to reduce the primary tumor volume (i.e.,cytoreductive therapy), which could improve local control and, therefore, decrease metastatic disease
  4. 4. RTOG 83-07 (megestrol and diethylstilbestrol with RT in a phase II randomized study) --- Both the megestrol and DES in addition to RT resulted in a high likelihood of clearance of the primary tumor (94% to 97%) and local regional tumor control (93% and 94%). Unfortunately, there were significant side effects especially in regard to the DES (i.e., cardiovascular events). LHRH agonists and nonsteroidal antiandrogens
  5. 5. RTOG study 85-19, which utilized these agents for patients with locally advanced disease, found them to be well tolerated and resulted in a high rate of tumor clearance (100%) RTOG and EORTC Trials These trials addressed two questions with regard to the use of androgen suppression and RT (i.e., the roles of adjuvant and neoadjuvant androgen deprivation)
  6. 6. TAS= Flutamide 250 mg tds Goserelin monthly x 4 m
  7. 7. RTOG 92-02 OS benefit was observed in patients with Gleason score 8 to 10 (Along with RT)
  8. 8. Hot flashes(50-80 %), sexual dysfunction (universal), gynaco mastia (20%) and decreased libido(universal) owing to the decrease in testosterone. In addition, with longer duration LHRH therapy, patients can develop increased fat mass, decreased lean body mass, and increased waist circumference. Understanding the concerns about weight gain and resultant health issues such as diabetes and cardiovascular disease, several authors have looked at the large randomized trials to understand whether there is truly an increase risk of fatal cardiovascular events with RT and LHRH therapy.
  9. 9. ? Life threatening complications RTOG 85-31 and 86-10, EORTC did not report any such events in both the arms EORTC 22961 and RTOG 92-02 showed no difference in the risk of CVS events in short term or long term ADT. Some authors have challenged these results with a follow up of 12 months Increased S/c fat Increased HDL Increased adiponectin levels No change in CRP Insulin sensitivity Which is different from Metabolic syndrome
  10. 10. But LHRHs donot appear to cause these met changes Caution in patients with obesity and pre existing CVS diseases Most important : Loss of BMD and a baseline DEXA scan before ADT with prophylaxis National Osteoporosis Guidelines recommend Calcium and Vit D3 Supplements for all men > 50 yrs on ADT FRAX tool (WHO) to assess risk of fractures Denosumab (60 mg s/c every 6 m) or Zoledronic acid 5mg IV annually or alendronate 70 mg P/o weekly increase the BMD during ADT ( when the absolute fracture risk warrants drug therapy)
  11. 11. Antiandrogens : Bicalutamide 50 mg P/o Flutamide 250 mg P/o Nilutamide 300 mg d1-d28 f/b 150 mg as maint. Abiraterone Estrogens : fosfestrol (hormone refractory) GnRH antagonists : Degarelix 240 mg S/c stat then 80 mg S/c every 28 days LHRH analogues : Goserelin 10.8 mg s/c 3 monthly or 3.6 mg S/c monthly Leuprolide 7.5 mg IM monthly or 22.5 mg 3 monthly or 30 mg 4 monthly
  12. 12. Treatment volumes for locally advanced prostate cancer have included the prostate and seminal vesicles plus a margin along with the pelvic lymph nodes. All the large randomized trials have treated the involved tissues in this fashion using doses to the lymph nodes of 45 to 50 Gy (four-field box technique and dose prescribed to isocenter) with a boost to the prostate totaling approximately 70 Gy (isocenter dose) ?benefit from dose escalation for these patients ? Treatment of pelvic nodes a must
  13. 13. RTOG 94-13 1323 patients , randomized into three groups WPRT versus prostate-only EBRT (PORT) and neoadjuvant 4 months of total androgen suppression versus adjuvant 4 months of total androgen suppression No difference in WPRT versus PORT and no statistical difference between neoadjuvant total androgen suppression versus adjuvant total androgen suppression
  14. 14. Showed an unexpected interaction between the timing of the total androgen suppression and the extent of the EBRT field. Progression-free survival was better in the WPRT and neoadjuvant total androgen suppression study arm versus the other three groups. However, this trial was unable to answer, in a definitive way, the WPRT versus PORT question because of the unexpected interactions. Therefore the question of WPRT versus PORT still needs to be evaluated in a prospective trial Till then the Standard of care would be NAHT+WPRT --- Adj ADT 2-3 yrs.
  15. 15. ? benefit was solely due to ADT and not RT SPCG-7 & SFUO-3 (Phase III RCTs) 875 patients (Scandinavian) TAS for 3 months followed by androgen deprivation with flutamide indefinitely versus the same androgen deprivation plus EBRT. EBRT statistically increased the 10-year prostate CSS compared with the androgen deprivation alone study arm and statistically increased OS with very acceptable toxicity rates.(Overall mortality rate at 10 y 39.4 % for ADT vs 19.6 % for RT and HT arm) Similar study by NCI Canada (life long ADT vs ADT + RT; 1205 pts; CSM was 23% vs 15% at 10 y )
  16. 16. External beam RT Positioning : RCT : In the supine position, prostate movements during normal breathing were less than 1 mm in all directions. Hence it is preferred. CT simulation in full bladder and empty rectum Mild laxatives and diet modification during planning and treatment MRI whenever feasible. CT overestimates prostate volume by 5%
  17. 17. Primary Therapy : Clinical Target Volume : Pretherapy tumour related factors Extra prostatic extension , Seminal Vesicle Inv. Predictive nomograms and risk factors decide whether adjacent normal tissue should be included in the CTV The average radial EPE distance from the capsule was 0.8mm in a study ( Davis et al.) Elective Nodal Irradiation when the risk of LNI reaches or exceeds 15 % ENI : to include the obturator , internal and external iliac lymphnodes
  18. 18. Planning Target Volume: Setup errors, organ movements , bladder and bowel volumes leading to target miss Monitoring can be done in many ways (USG, CBCT , implanted fiducials, implanted electro magnetic transponders) Range of PTV 0.5 to 1 cm With out setup correction margin of 11 to 15mm With daily imaging – 8mm to 13mm With implanted fiducial markers – 3 mm – 8mm (around prostate and seminal vesicles) Using an endorectal balloon daily may position the gland (air redices the rectal surface dose with buildup at the air and soft tissue interface)
  19. 19. 2 D planning : (1) superior: L5-S1 interspace; (2) inferior: bottom of ischial tuberosities; (3) lateral: 2 cm lateral to pelvic inlet; (4) anterior: approximately 1 cm anterior to the anterior projection of the pubic symphysis; and (5) posterior: S3-4 interspace.
  20. 20. Prostate and Seminal Vesicles
  21. 21. Contouring of Prostate and Seminal Vesicles
  22. 22. Contouring of Prostate and Seminal Vesicles Contnd..
  23. 23. Pelvic LNs
  24. 24. Contouring of Pelvic nodes
  25. 25. Contouring of Pelvic nodes Contind…
  26. 26. 3 D CRT or IMRT ( Preferred) ; IGRT in case if Dose prescription > 78 Gy Doses upto 81 Gy provide improved Biochemical control LNI is a must in high risk and locally advanced cases Treatment results appear better when disease burden is lower. Therefore RT should be started before PSA exceeds 0.5 ng/ml Image guided / organ localization based techniques are preferred.
  27. 27. Dose Constraints Definitive Therapy ( MSKCC; 81 Gy)
  28. 28. Adverse pathological / lab features : Positive margins Seminal vesicle invasion ECE Detectable PSA pT3 disease Gleason score 8 -10 Or as Salvage
  29. 29. Adjuvant RT / Salvage RT
  30. 30. Adjuvant RT / Salvage RT
  31. 31. Adjuvant RT / Salvage RT
  32. 32. Indicated in adverse path features ; detectable PSA with no evidence of disseminated disease Usually given within 1 year after RP and once operative side effects are minimized Salvage therapy is indicated in detectable PSA that increases on 2 subsequent occasions . Most effective if pre treatment PSA is < 1 ng /ml Recommended dosage : 64 to 68 Gy in std fractionation Defined target volume is the prostate bed Inclusion of pelvic nodes can be considered but not necessary.
  33. 33. Dose Constraints : OARs
  34. 34. RP + PLND No fixation If adverse features are + ------ RT / Observation LN + ------- ADT / observation / ADT + Pelvic RT (Category 2B)
  35. 35. The T half of PSA is 3.1 days PSA should be undetectable 4 weeks or more after RP ‘PSA doubling time’ expressed as the velocity in nanograms/ml/year, or the PSA doubling time, in months or years. The most important values to enter are the date/PSA value for each PSA measured over the last 12 months. Alternately, if at least three PSA values are available, enter all PSA values after receiving radical prostatectomy, beginning with the lowest PSA value. The calculator is available at http://nomograms.mskcc.org/Prostate/PsaDoublingTime.aspx
  36. 36. Further RTOG –ASTRO phoenix consensus defined Biochemical failure as After EBRT with or without HT : PSA rise by 2 ng/ml or more above the nadir PSA The date of PSA is calculated at call and not back dated.
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Locally advanced Ca prostate Courtesy : NCCN , Perez, Gunderson and Tepper Brief outline on management ADT, Radiotherapy, Surgery indications and Standard of care

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