Introduction Treatment of metastatic prostate cancer with androgen deprivation therapy (ADT) is...
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Introduction Treatment of metastatic prostate cancer with androgen deprivation therapy (ADT) is effective, but can be associated with debilitating side effects. Oligometastasis describes a state of limited metastatic capacity (Weichselbaum 2011). This may represent an intermediate disease state that is amenable to aggressive local therapy, allowing deferral of ADT. In practice oligometastasis usually refers to five or fewer metastases. These early metastatic lesions may seed further metastases. Therefore, eradication of oligometastases may alter the progression of disease and potentially offer cure in select cases. Surgery or radiation therapy are the two treatment options in this setting. Stereotactic body radiotherapy (SBRT) is relatively non- invasive. It delivers an ablative dose of radiotherapy to target tissues, minimising scatter to adjacent structures. Early evidence in other cancers suggests SBRT is a safe and effective treatment for oligometastatic disease (Tree 2013). Conclusions This promising early data suggests that SBRT has the potential to safely control oligometastatic prostate cancer in the short term, and may delay the need for ADT and its associated side effects. Longer follow-up and prospective controlled trials are warranted. Results Methods A retrospective review was undertaken of all men with oligometastatic prostate cancer (≤5 sites of metastasis), treated with SBRT by one clinician (PB) from Dec 2007 to Dec 2013. Outcomes included effectiveness and safety of SBRT. Efficacy was measured by ADT use and biochemical response (PSA). Biochemical failure was defined as two consecutive PSA rises, a single PSA rise >50% of pre-SBRT level, or no absolute reduction in PSA. Cases studies were also undertaken of two men with complete biochemical response to SBRT. Results reported are median and range unless otherwise stated. Aim To evaluate the effectiveness of SBRT in oligometastatic prostate cancer. References • Tree, A. et al. Stereotactic body radiotherapy for oligometastases. Lancet Oncology 2013; 14, e28–e37 • Weichselbaum, R.R. & Hellman, S. Oligometastases revisited. Nature reviews. Clinical oncology 2011; 8(6), 378–382 Fairleigh Reeves 1 , Patrick Bowden 2 , Anthony Costello 1,2 1 The Royal Melbourne Hospital; 2 Epworth Hospital Richmond, Australia Stereotactic body radiotherapy in the treatment of oligometastatic prostate cancer: early results Results Patient Characteristics Primary Cancer PSA ug/L 9.1 (2.4- 96) Gleason 8 (6-9) Stage T1c T2a T2c T3a T3b 6% 6% 17% 34% 37% Primary Rx RP RP + RT RT 32% 46% 22% SBRT Age 69y (50-80) Time to SBRT from 1° Rx 39month s (6wk- 13y) ADT status Naïve *Use(d) CRPC 62% 14% 24% Symptomat ic 15% Lesion type Bone Node Both 59% 37% 5% Number sites 1 2 4 0r 5 71% 22% 7% Treatment details Lesion Gray Fraction Overall 36.84 (12-70) 10 (1-35) Lymph Node 35.5 (18-70) 5 (3-35) Case 1 – 62yo March 2010 RARP (Gleason 8, PSA 6.5, staging negative) • Post-op PSA <0.01ug/L increased to 0.21 (Oct 2011) December 2011 Salvage prostate bed radiotherapy • Feb 2013 Ongoing PSA rise to 7.1 with back pain • Bone scan solitary lumbar vertebral metastasis March 2013 SBRT to lumbar metastasis • Follow-up PSA 0.35 (6wk), 0.091 (8months) • Remains ADT free Case 2 – 58yo August 2007 RARP (Gleason 7, PSA 39, staging negative) • Oct 2007 Post-op PSA 43.3ug/L, back pain • Bone scan solitary lumbar vertebral metastasis December 2007 High dose RT to lumbar lesion + ADT • August 2008 PSA <0.01 Intermittent ADT • April 2012 PSA rise to 8.5 (HORMONE REFRACTORY) • Bone scan new acetabular metastasis no uptake in previously treated lesion May 2012 High dose RTto acetabular metastasis • Feb 2013 ADT ceased • Aug 2013 PSA 0.038 off ADT (S.Testosterone 7.4nmol/L) • 41 treatments in 37 men • Median follow-up 5 months (6wkto 4.3y) • Metastases were detected on Bone Scan, CT, PET or MRI *Use(d) = current/previous ADT excluding CRPC and neoadjuvant/adjuvant ADT only Initial PSA follow-up in all patients ADT status Pre-SBRT 6/52 review Overall 7 (<0.01 – 81.51) 4.9 (<0.01 – 60) Naïve 6.65 (0.75 – 43) 4.8 (0.217 – 60) *Use(d) 18.7 (<0.01 – 81.51) 6.74 (<0.01 – 59.1) CRPC 10 (4 – 72) 4.5 (0.02 – 27.5) Clinical Outcomes All patients with >1 follow-up PSA (n=31) • 42% Biochemical response • 13% Biochemical failure not requiring treatment • 45% Biochemical failure requiring SBRT, ADT or chemotherapy ADT naïve patients (n=23) • 16 PSA response remain ADT free • 4 started ADT (6wk – 6m post SBRT) • 3 required further SBRT • 1 started ADT (6m post SBRT) • 2 remain ADT free • Overall 78% remain ADT free at 5 months (median) Symptomatic patients (n=6): 83% had resolution of their pain Acute toxicity (all patients) • 61% no toxicity • 31.7% minor side effects not requiring treatment (Grade1) • 7.3% nausea or diarrhoea requiring medication (Grade2) Case 2 2007 Case 3 2012 Case 1 2013
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Transcript of Introduction Treatment of metastatic prostate cancer with androgen deprivation therapy (ADT) is...
IntroductionTreatment of metastatic prostate cancer with androgen deprivation therapy (ADT) is effective, but can be associated with debilitating side effects.
Oligometastasis describes a state of limited metastatic capacity (Weichselbaum 2011). This may represent an intermediate disease state that is amenable to aggressive local therapy, allowing deferral of ADT. In practice oligometastasis usually refers to five or fewer metastases. These early metastatic lesions may seed further metastases. Therefore, eradication of oligometastases may alter the progression of disease and potentially offer cure in select cases.
Surgery or radiation therapy are the two treatment options in this setting. Stereotactic body radiotherapy (SBRT) is relatively non-invasive. It delivers an ablative dose of radiotherapy to target tissues, minimising scatter to adjacent structures. Early evidence in other cancers suggests SBRT is a safe and effective treatment for oligometastatic disease (Tree 2013).
ConclusionsThis promising early data suggests that SBRT has the potential to safely control oligometastatic prostate cancer in the short term, and may delay the need for ADT and its associated side effects. Longer follow-up and prospective controlled trials are warranted.
Results
MethodsA retrospective review was undertaken of all men with oligometastatic prostate cancer (≤5 sites of
metastasis), treated with SBRT by one clinician (PB) from Dec 2007 to Dec 2013.Outcomes included effectiveness and safety of SBRT. Efficacy was measured by ADT use and
biochemical response (PSA). Biochemical failure was defined as two consecutive PSA rises, a single PSA rise >50% of pre-SBRT level, or no absolute reduction in PSA.
Cases studies were also undertaken of two men with complete biochemical response to SBRT.Results reported are median and range unless otherwise stated.
AimTo evaluate the effectiveness of SBRT in oligometastatic prostate cancer.
References• Tree, A. et al. Stereotactic body radiotherapy for oligometastases. Lancet Oncology 2013; 14,
e28–e37• Weichselbaum, R.R. & Hellman, S. Oligometastases revisited. Nature reviews. Clinical oncology
2011; 8(6), 378–382
Fairleigh Reeves1, Patrick Bowden2, Anthony Costello1,2
1The Royal Melbourne Hospital; 2Epworth Hospital Richmond, Australia
Stereotactic body radiotherapy in the treatmentof oligometastatic prostate cancer: early results
Results
Patient Characteristics
Primary Cancer
PSA ug/L 9.1 (2.4-96)
Gleason 8 (6-9)
StageT1cT2a T2cT3a T3b
6%6%17%34%37%
Primary RxRPRP + RTRT
32%46%22%
SBRT
Age 69y (50-80)
Time to SBRT from 1° Rx
39months (6wk-13y)
ADT statusNaïve*Use(d)CRPC
62%14%24%
Symptomatic 15%
Lesion typeBone Node Both
59%37%5%
Number sites124 0r 5
71%22%7%
Treatment details
Lesion Gray Fraction
Overall 36.84 (12-70) 10 (1-35)
Lymph Node 35.5 (18-70) 5 (3-35)
Bone 40 (12-50) 10 (1-20)
Case 1 – 62yoMarch 2010 RARP (Gleason 8, PSA 6.5, staging negative)• Post-op PSA <0.01ug/L increased to 0.21 (Oct 2011)December 2011 Salvage prostate bed radiotherapy• Feb 2013 Ongoing PSA rise to 7.1 with back pain• Bone scan solitary lumbar vertebral metastasisMarch 2013 SBRT to lumbar metastasis• Follow-up PSA 0.35 (6wk), 0.091 (8months)• Remains ADT free
Case 2 – 58yo August 2007 RARP (Gleason 7, PSA 39, staging negative)• Oct 2007 Post-op PSA 43.3ug/L, back pain• Bone scan solitary lumbar vertebral metastasisDecember 2007 High dose RT to lumbar lesion + ADT• August 2008 PSA <0.01 Intermittent ADT• April 2012 PSA rise to 8.5 (HORMONE REFRACTORY)• Bone scan new acetabular metastasis no uptake in
previously treated lesionMay 2012 High dose RTto acetabular metastasis• Feb 2013 ADT ceased• Aug 2013 PSA 0.038 off ADT (S.Testosterone 7.4nmol/L)
• 41 treatments in 37 men • Median follow-up 5 months (6wkto 4.3y)• Metastases were detected on Bone Scan, CT, PET or MRI
*Use(d) = current/previous ADT excluding CRPC and
neoadjuvant/adjuvant ADT only
Initial PSA follow-up in all patients
ADT status Pre-SBRT 6/52 review
Overall 7 (<0.01 – 81.51) 4.9 (<0.01 – 60)
Naïve 6.65 (0.75 – 43) 4.8 (0.217 – 60)
*Use(d) 18.7 (<0.01 – 81.51) 6.74 (<0.01 – 59.1)
CRPC 10 (4 – 72) 4.5 (0.02 – 27.5)
Clinical OutcomesAll patients with >1 follow-up PSA (n=31)• 42% Biochemical response• 13% Biochemical failure not requiring treatment• 45% Biochemical failure requiring SBRT, ADT or chemotherapy
ADT naïve patients (n=23)• 16 PSA response remain ADT free• 4 started ADT (6wk – 6m post SBRT)• 3 required further SBRT
• 1 started ADT (6m post SBRT)• 2 remain ADT free
• Overall 78% remain ADT free at 5 months (median)
Symptomatic patients (n=6): 83% had resolution of their pain
Acute toxicity (all patients)• 61% no toxicity• 31.7% minor side effects not requiring treatment (Grade1)• 7.3% nausea or diarrhoea requiring medication (Grade2)
Case 2 2007
Case 3 2012
Case 1 2013
