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Post treatment surveillance for Genitourinary Cancers

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Post treatment surveillance for Genitourinary Cancers

  1. 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. 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. 3. Natural history of prostate cancer
  4. 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. 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. 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. 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. 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. 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. 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. 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. 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)
  13. 13. ASCO 2018
  14. 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. 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. 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. 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. 18.  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
  19. 19. 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
  20. 20. 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
  21. 21. 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
  22. 22. Testicular Tumors
  23. 23. 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
  24. 24. 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
  25. 25. 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
  26. 26. Thank you!!

Notas do Editor

  • 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

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