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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
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
Natural history of prostate cancer
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
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
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
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
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
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
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
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)
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)
ASCO 2018
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%
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
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
 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.
Post treatment surveillance for Genitourinary Cancers
 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
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
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
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
Testicular Tumors
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
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
Post treatment surveillance for Genitourinary Cancers
Post treatment surveillance for Genitourinary Cancers
Post treatment surveillance for Genitourinary Cancers
Post treatment surveillance for Genitourinary Cancers
Post treatment surveillance for Genitourinary Cancers
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
Thank you!!

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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
  • 3. Natural history of prostate cancer
  • 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.
  • 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
  • 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

Editor's Notes

  1. The predictors of metastasis are Gleason score of 8–10, pathological stage T3b-4, nodal invasion and prostate-specific antigen (PSA) doubling time.
  2. 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