This document discusses locally advanced high risk prostate cancer and evolving treatment options. It provides an overview of risk stratification, guidelines for biopsy from the European Association of Urology, options for imaging with multiparametric MRI, and options for treatment including radical prostatectomy, radiation therapy, and hormonal therapy. New advances in radiation therapy include stereotactic body radiation therapy and hypofractionated regimens. Advances in hormonal therapy include gonadotropin-releasing hormone antagonists and oral options like relugolix. Neoadjuvant docetaxel chemotherapy is also discussed for high risk localized disease.

1. Locally Advanced High Risk Prostate Cancer -
Current SOC and Evolving Treatment options
DR KANHU CHARAN PATRO
MD,DNB(RADIATION ONCOLOGY),MBA,FAROI(USA),PDCR,CEPC
HOD,RADIATION ONCOLOGY
Mahatma Gandhi Cancer Hospital And Research Institute, Visakhapatnam
drkcpatro@gmail.com M-9160470564
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2. RISK STRATIFCATION
Definition
Low Risk Intermediate Risk High Risk
PSA < 10 ng/mL PSA 10-20 ng/mL PSA > 20 ng/mL any PSA
and GS < 7 (ISUP grade 1) or GS 7 (ISUP grade
2/3)
or GS > 7 any GS
and cT1-2a or cT2b or cT2c cT3-4 or cN+
Localized Locally advanced
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3. RISK ASSESMENT- GPS
1. Gleason score, PSA, and Stage are more useful tool
2. Ability to assess pathologic stage permits better pre-
treatment counseling of patients,
1. More appropriate selection of therapy
2. Consideration of those with more advanced disease for novel
clinical trials.
3. Most important pathologic criteria predicting prognosis
after RADICAL PROSTATECTOMY are
1. Gleason score, surgical margin status, and presence of non–
organ- confined disease (e.g.extracapsular extension, seminal
vesicle invasion, lymph node involvement).
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4. EUROPEAN ASSOCIATION OF UROLOGY GUIDELINES FOR BIOPSY
EUA GUIDELINE UPDATES 21st AUGUST 2021/PROSTATE
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5. EUROPEAN ASSOCIATION OF UROLOGY GUIDELINES FOR BIOPSY
EUA GUIDELINE UPDATES 20th AUGUST 2021/PROSTATE
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6. ESMO
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9. IMAGING
• Multiparametric MRI (mpMRI)
– Enables reliable detection of clinically significant
cancers
– Is currently the leading imaging modality:
• For the detection, characterization, and local
staging of prostate cancer.
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10. OPTIONS OF THE TREATMENT
• Radical Prostatectomy
• Neo-Adjuvant Androgen Deprivation
• Radiation Therapy
– EBRT
– BRACHY
• Adjuvant ADT
• Adjuvant Chemotherapy
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12. ESMO OPTIONS
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13. WHAT ESMO SAYS
• Primary ADT alone is not recommended as standard
initial treatment for non-metastatic disease [I, D].
• External beam RT plus ADT is recommended for men
with high-risk or locally advanced prostate cancer [I, B].
• RP plus pelvic lymphadenectomy is an option for
selected men with high-risk disease [III, B].
• Men receiving radical RT for high-risk disease should
have long-course ADT (18 to 36 months) [I, A].
• Neoadjuvant docetaxel may be offered before RT for
young, fit men with very high-risk localised prostate
cancer [I, C].
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14. WHAT ESMO SAYS
• Following RP, patients should have their serum PSA level monitored, with
salvage RT recommended in the event of PSA failure [III, B].
• Adjuvant postoperative RT after RP is not routinely recommended [I, B].
• Salvage RT should start early (e.g. PSA < 5ng/ml[III,B]
• Concomitant ADT for 6 months or bicalutamide 150 mg daily for 2 years
may be offered to men having salvage RT [I, B].
• Men having SRT to the prostate bed may be offered pelvic nodal RT [I, C].
• Men with biochemical relapse after radical RT who may be candidates for
local salvage or metastasis-directed treatment should undergo imaging
with PET-CT [III, B].
• Early ADT alone is not recommended for men with biochemical relapse
unless they have a rapid PSA doubling time, symptomatic local disease or
proven metastases [II, D].
• Men starting ADT for biochemical relapse, in the absence of metastatic
disease, should be offered intermittent rather than continuous treatment
[I, B].
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15. ADVANCES IN RADIOTHERAPY
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16. WHY SBRT FOR PROSTATE CANCER?
EUA GUIDELINE
UPDATES
21st AUGUST 2021/PROSTATE
1. Low alpha/beta ratio of 1.5-1.8 (CHHiP trial and Perez and Brady)
2. If the alpha/beta for dose-limiting normal tissue is less than that of the tumor, larger fraction sizes preferentially kill
the tumor compared to normal tissue
3. Increased patient convenience
4. Increased access for underserved patient populations (long commute etc)
5. More cost-effective than other EBRT fractionation schedules
6. NCCN 2020: very low, low, favorable intermediate, unfavorable intermediate, high, very high-risk prostate cancer
and low volume M1 disease
7. ASTRO, ASCO and AUA 2018: low and intermediate risk disease
8. 2020 COVID19 pandemic recommendation: 5- to 7- fraction SBRT is preferred for localized prostate cancer that
requires treatment
9. HYPO-RT-PC trial
1. SBRT (42.7 Gy in 7 fractions) vs conventional fractionation (78 Gy in 39 fractions) with no ADT
10. PRIME TRIAL
1. SBRT: 36.25Gy in 5 fractions over 7–10 days; (node-positive disease - 25Gy in five fractions) versus moderate
hypofractionation: 68Gy in 25 fractions over 5 weeks; (node-positive disease – 50Gy in 25 fractions
11. PACE B TRAIL
1. SBRT (36.25 Gy in 5 fractions with a concomitant boost to 40 Gy) vs conventionally fractionated or
moderately hypofractionated EBRT (78 Gy in 39 fractions or 62 Gy in 20 fractions) with no ADT
12. NRG GU005
1. Stereotactic Body Radiation Therapy or Intensity Modulated Radiation Therapy in Treating Patients With
Stage IIA-B Prostate Cancer
13. HEAT-Radiation Hypofractionation Via Extended Versus Accelerated Therapy
1. 70.2 Gy in 26 fractions vs 36.25 Gy in 5 fractions in Low and intermediate risk disease included
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17. PHASE III TRIALS IN PROSTATE CANCER
VEDANG MURTHY/BMJ
OPEN/2020
23rd AUGUST 2021/PROSTATE
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20. Single-Dose Radiotherapy in Patients With Intermediate-Risk Prostate Cancer
Carlo Greco/JAMAONCOLOGY/2021 18th AUGUST 2021/PROSTATE
1. This randomized phase II trial evaluated the feasibility of ultra-high single-dose
radiation therapy at 24 Gy compared with standard hypofractionated curative
radiation (5 x 9 Gy) in men with intermediate-risk prostate cancer confined to the
prostate.
2. Acute urinary frequency and dysuria, grade 1, were noted in 40% of single-dose
radiation recipients and 27% of standard stereotactic body radiation therapy
(SBRT) recipients.
3. In both arms, symptoms had resolved within 4 weeks of radiation therapy.
4. There was no significant difference in the cumulative late genitourinary toxic
effects between the two groups (HR, 1.07 for grade 2 or higher).
5. There were similar PSA declines over the duration of follow-up for the two
treatment arms.
6. The 48-month actuarial biochemical relapse–free survival was 85.7% in the SBRT
group and 77.1% in the single-dose radiation group (HR, 0.69).
7. These results indicate that single-dose radiation may be safe and effective among
patients with intermediate-risk organ-confined prostate cancer.
PROSINT TRIAL
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21. ADVANCES IN POST OP RADIOTHERAPY
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22. WHAT IS DOUBLE TROUBLE?
• Most of the post op prostate patients require radiation
• Why we should choose surgery, where hypofractionation
radiation of 20 days available with equal results with
conventional radiotherapy?
• It is double trouble when we add radiotherapy after surgery
as dual toxicity.
• Let’s discuss in detail
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30. CONCLUSION
• Surgery also a mode of treatment
• Careful selection is the key point
• Side effects of surgery takes more time to
recover.
• Hypofractionation radiotherapy is the best I
feel.
• Do not invite double trouble because you may
not able to troubleshoot always .
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31. ADVANCES IN HORMONAL THERAPY
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32. CHANGES IN HORMONAL THERAPY
• GnRH analogue
– Luperolide
• GnRH antagonist
– Degarelix
– Relugolix [oral]
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34. 26th AUGUST 2021/PROSTATE
Mohammad Abufaraj /EUROPEAN UROLOGY/2021
GNRH AGONIST VS ANATGONIST IN MET.PROSTATE CA.A METAANALYSIS
1. Androgen deprivation therapy is the mainstay treatment of metastatic prostate cancer,
achieved mainly by gonadotropin-releasing hormone (GnRH) agonists or antagonists.
2. Gonadotropin-releasing hormone (GnRH) antagonist is associated with lower death rates
and cardiovascular events than GnRH agonists, based on the data from trials with short
follow-up duration.
3. GnRH agonists are associated with lower adverse events, such as decreased libido, hot
flushes, erectile dysfunction, back pain, weight gain, constipation, and injection site reactions.
4. There were no significant differences in PSA progression or fatigue
5. On the contrary, injection site reactions were higher in patients treated with GnRH antagonist
6. GnRH antagonist was associated with lower overall mortality rates than GnRH agonists (RR:
0.48, 95% CI: 0.26–0.90, p = 0.02)
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35. HERO study
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36. HERO study
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37. HERO study
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38. HERO study
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39. • Relugolix achieved castration as early as Day
4 and demonstrated superiority over
leuprolide in sustained testosterone
suppression through 48 weeks
• Relugolix also had faster testosterone
recovery after discontinuation and a 54%
reduction in MACE
• Relugolix has the potential to become a new
standard for testosterone suppression for
patients with advanced prostate cancer
HERO study
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40. ADVANCES IN CHEMOTHERAPY
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41. Neoadjuvant docetaxel for M0 disease
• GETUG-12
• RTOG 0521
• STAMPEDE
• SPCG-12,
• SPCG-13
• VA Cooperative Study Program (CSP)
#553
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44. OS
FFS
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45. GUIDELINES FOR SECOND-LINE THERAPY AFTER TREATMENT WITH CURATIVE INTENT
EUA GUIDELINE UPDATES 22nd AUGUST 2021/PROSTATE
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