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Post treatment surveillance for Genitourinary Cancers
1. Dr Ajeet Kumar Gandhi
MD (AIIMS), DNB (Gold Medalist), UICCF (MSKCC,USA)
Assistant professor, Radiation oncology
Dr RMLIMS, Lucknow
Post treatment surveillance in GU
(Prostate and Testis) cancers
2. Prostate cancer: Management
Risk Category Management
Low Active Surveillance
Radical Prostatectomy ± Pelvic LN dissection
Brachytherapy
Radical EBRT
Intermediate Radical EBRT + Short term ADT
EBRT + Brachytherapy boost + Short term ADT
Radical Prostatectomy ± Pelvic LN dissection
Brachytherapy
High Radical EBRT + long term ADT
EBRT + Brachytherapy boost + long term ADT
Radical Prostatectomy + Post op RT
4. Ideal post treatment surveillance
program
Goals of therapy: shared decision making
Predictions for future natural course of disease
Discussions about salvage treatment available
Survivorship program
5. Post-treatment tool kit for surveillance:
Prostate Cancer
Serum PSA
Digital Rectal Examination (Low specificity)
Imaging
TRUS :Poor specificity
MRI
Prostate specific PET imaging
Post treatment prostate biopsies
6. Biochemical failure
10-40 % of patients with recurrent PSA will develop
systemic progression*
PSA relapse precedes clinical failure by a number of
years
PSA rise indicates recurrence but does not distinguish
between local and distant relapse
5 year survival after post RT PSA recurrence: 60-70%
*Boorjian et al. Eur Urol. 2011;59:893–
9
7. Predictive factors for BCF
Positive surgical margins
PSA recurrence <2 years, Gleason 8-10 and PSADT <10
months
PSA-DT of <12 months and an interval of <12 months
from end of radiotherapy to PSA rise as significant
independent predictors of distant failure
*Perez and Brady, 6th edition
8. PSA in post treatment setting:
What is normal
After RP: Levels should be undetectable. Wait for 6-8 weeks
(ACS)
After Radical RT: PSA less than 0.5 ng/ml or Undetectable
Disease recurrence likely:
Doubles in less than six months
Rises within 12 months of any form of treatment
*AUA policy report on PSA monitoring
9. PSA in post treatment setting:
What is normal
ASTRO: Three consecutive rise in serum PSA above nadir. Not
more than 3-6 months interval. Applicable only to patients treated
with EBRT with or without short term hormonal therapy. Sensitivity
64% & Specificity 78%
Metastatic prostate cancer:
Undetectable PSA or PSA decrease by more than 90% at 3-6
months predict PFS
>50% decrease in PSA at 8 weeks after secondary therapy
PSA trigger for bone scan (following initial treatment of localized
prostate cancer): 40-45 ng/ml
*AUA policy report on PSA monitoring
10. PSA: After hormonal therapy
ADT can decrease the serum level of PSA
independent of tumour response
Reduction of PSA to undetectable levels (duration of
PFS)
Decreases in PSA of less than 80% may not be very
predictive
Clinical criteria should also be followed
11. Post treatment surveillance: PSA
PSA Bounce:
Def (IJROBP 2006:64;512-517): Increased PSA >0.2ng/ml
from nadir & subsequent fall
Median time: 18-26 months (occurs sooner than true
PSA relapse; 22-30 months)
Fluctuation range: 0.11-15.8 ng/ml
More common with EBRT plus Brachytherapy (30-40%)
EBRT alone (12-30%)
Prognostic value: Superior (Rosser et al. J Urol
2002;168:2001-05)
12. Post treatment surveillance: PSA
Post treatment PSA doubling time (PSADT)
After RP: <10 months (development of metastatic
disease)JAMA 1999; 281:1591-7
After EBRT (Zelefsky et al. J Clin Onc 2005;23:826-
831)
The PSADT for favorable-, intermediate-, and
unfavorable-risk patients who developed a
biochemical failure was 20.0, 13.2, and 8.2
months, respectively (p < .001).
The 3-year incidence of DM for patients with
PSADT of 0 to 3, 3 to 6, 6 to12, and >12 months
was 49%, 41%, 20%, and 7%, respectively (p <
.001)
14. Role of MRI in recurrent prostate cancer
T2 weighted imaging: sensitivity 84.1-88%, specificity
52-82%
T2 combined with dynamic imaging: Sensitivity 84.1-
88%; Specificity 89.3-100%
Dynamic MRI with spectroscopy: Sensitivity 87%;
Specificity 94%
15. Prostate cancer specific PET
radiotracers
pcPET radiotracers in the setting of biochemical
recurrence:
Carbon 11/fludeoxyglucose 18(F-18) choline
Gallium 68/F-18 prostate specific membrane antigen
(PSMA)
F-18 fluciclovine
PSMA PET more useful:
Median 51.5% of patients when PSA level is <1.0 ng/mL
74%of patients when PSA level is 1.0 to 2.0 ng/mL
90.5% of patients when PSA level is >2.0 ng/mL
16. Prostate biopsy after RT
20-80% biopsy positivity rate in T1-T3 prostate cancers*
Associated with higher nadir PSA, higher rate of local
recurrence
6 year BFFS 95% vs. 70% in biopsy positive versus negative
after definitive RT**
Biopsy time: 24-36 months after RT***
Rising PSA without systemic disease but with positive
biopsy: Potential candidates for salvage therapy
*Hammer P et al. European Urology 2002; 83-88
**Stoyanova et al. IJROBP 2012:84 (3): S60
*** Juniata crook et al. IJROBP 2000;48(2):355-367
17. Clinicians should monitor localized prostate cancer patients
post therapy with PSA, even though not all PSA recurrences are
associated with metastatic disease and prostate cancer specific
death.
Clinicians should inform localized prostate cancer patients of
their individualized risk-based estimates of post-treatment
prostate cancer recurrence.
Clinicians should support localized prostate cancer patients
who have survivorship or outcome concerns by facilitating
symptom management and encouraging engagement with
professional or community based resources.
18.
19. Prostate cancer recurrence: PSA every 6-12 months for 5
years and then annually (more frequently in high risk
individuals). Annual DRE
Health promotion: 150 mins of physical activity, 600 IU of
vitamin D per day, calcium (<1200mg/day), limit alcohol and
tobacco
Screening for second primary cancers: bladder and
colorectal cancer
For patients with ADT: Anemia, Osteoporosis, Sugar, Lipids,
CVS, Vasomotor symptoms
Sexual dysfunction, intimacy, urinary dysfunction, anxiety
and distress
20. Routine DRE after local therapy is not required for
asymptomatic patients while the PSA remains controlled
Biopsy of the prostate after RT should only be carried out in
men with prostate cancer who are being considered for
salvage local therapy
Men on long-term ADT should be monitored for side-effects
including osteoporosis (using bone densitometry) and
metabolic Syndrome
In patients with CRPC on systemic treatment, regular
imaging studies should be done to monitor disease
response/progression
21. Rising PSA after radical
treatment
Def of PSA recurrence
Exclude PSA bounce
Look for other clinical factors, PSADT
Prior treatment received
Clinically significant PSA
recurrence
Imaging: MRI/ PET
Biopsy of local recurrent
lesion
Local recurrence
Patient suitable for salvage therapy
22. Conclusion I: Prostate
Serum PSA every 6-12 months (may be individualized
in selected cases)
Rising PSA should be interpreted keeping in account
other clinical factors
DRE every year
TRUS (unreliable), multi-parametric MRI/Prostate
specific PET useful in certain scenarios but not for
routine surveillance
Prostate biopsy/ biopsy of locally recurrent disease
in selected patients
24. Issues in testicular cancer
survivorship
Detection of relapse
High cure rates
Effective salvage therapies (almost >50% cured)
Relapses evident through rise in tumor
markers/radiological imaging
Tumor markers elevated in 2/3rd of NSGCT and 1/3rd of
Seminoma: Value in isolation questionable
25. Issues in testicular cancer
survivorship
Impairment in spermatogenesis:
Transient effect (6-12 months)
Recovery in most with testicular doses (9-50 cGY)
Second primary Cancers:
Risk in 10 year survivors: Almost twice
Increased risk of lung, esophagus, colon and pleura, leukemia
Increased risk of cardiac death
Chemotherapy induced long term side effects:
High tone hearing loss
Neurotoxicity, Reynaud's phenomenon, hypertension, renal
dysfunction
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31. Conclusion II-Testicular tumors
Post treatment surveillance: Individualized based on
stage and histology
History and physical examination, abdominal/pelvic CT,
Chest X-ray at varying intervals
Routine use of tumor markers/testicular USG is not
recommended
Focus on late effects mandatory
The predictors of metastasis are Gleason score of 8–10, pathological stage T3b-4, nodal invasion and prostate-specific antigen (PSA) doubling time.
Biochemical evidence of failure on the basis of elevated or slowly rising PSA alone, therefore, may not be sufficient to initiate additional treatment
For example, in a retrospective analysis of nearly 2,000 men who had undergone radical prostatectomy with curative intent and who were followed for a mean of 5.3 years, 315 men (15%) demonstrated an abnormal PSA of 0.2 ng/mL or higher, which is considered evidence of biochemical recurrence. Among these 315 men, 103 (34%) developed clinical evidence of recurrence. The median time to the development of clinical metastasis after biochemical recurrence was 8 years. After the men developed metastatic disease, the median time to death was an additional 5 years