Prostate Cancer and the Role of PostOp Radiation

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Information about Prostate Cancer and the Role of PostOp Radiation
Health & Medicine

Published on February 25, 2014

Author: doctorbobm

Source: slideshare.net

Description

The role of radiation in prostate cancer in men who have already had surgery

Prostate Cancer Radiation after Surgery Robert Miller MD www.aboutcancer.com

Is there ever a need for radiation after a man has already had his prostate removed PostOp Radiation (Adjuvant Therapy) if the pathology report from the surgery raises the concern: “was the cancer completely removed?” Salvage Radiation

PostOp Radiation (Adjuvant Therapy): if the pathology report from the surgery raises the concern: “was the cancer completely removed?” • How likely is it that the cancer will recur? • How effective is radiation in preventing this?

NCCN.org

NCCN Advice on PostOp Radiation RP (radical prostatectomy) PLND (pelvic lymph node dissection) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)

NCCN Advice on PostOp Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)

Adverse Features 1.Positive Surgical Margins 2.Invasion into the Seminal Vesicles 3.Extracapsular Extension 4.Detectable PSA (after surgery the PSA should fall to undetectable by a few weeks)

Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. Stamey TA After radical prostatectomy for cancer, PSA routinely fell to undetectable levels, with a half-life of 2.2 days. N Engl J Med. 1987 Oct 8;317(15):909-16. Prostate specific antigen in the preoperative and postoperative evaluation of localized prostatic cancer treated with radical prostatectomy. Oesterling JE the half-life of prostate specific antigen was calculated to be 3.15 days. J Urol. 1988 Apr;139(4):766-72

PSA Half Life of 3 days Surgery 6 12 Percentage 3 days 6 days 9 days 12 days 15 days 18 days 21 days 24 days 27 days 30 days 33 days 3 1.5 .75 .375 .1875 .0937 .0468 .0234 .0117 .0059 (<0.01) .0029 (<0.01) 6 3 1.5 .75 .375 .1875 .0937 .0468 .0234 .0017 .0059 (<0.01) 50% 25% 12.5% 6.25% 3.125% 1.5625% .0078% .0039% .0019% .00098% .00049% Takes 4 to 5 weeks to reach undetectable (<0.01) so most people wait 6 to 8 weeks after surgery to check the PSA level

Seminal Vesicles PROSTATE CAPSULE

Impact of Path Reporting Positive Surgical Margins Odds of a PSA Relapse Risk Group + Margins - Margins Low risk Intermediate High 5.1% 17% 43% J Urol. 2010;183(1):145. 0.4% 6.5% 21.5%

Impact of Path Reporting Positive Surgical Margins Odds of a PSA Relapse by 3 Years Solitary Apical Margin Solitary Non-apical margin Multiple positive margins 13.0% 18.6% 27.0%

aboutcancer.com/medical_calculators Adjuvant online has survival and benefit calculators for breast, colon, lung Breast cancer calculators here Cancer Risk: from Harvard, various types of cancer Cancer Risk from X-ray Exposure Colon cancer risk of Lynch syndrome from Dana Farber Colon Cancer risk from the NCI here Head and Neck cancer survival here Life Expectancy Calculators and Life Expectancy for the Elderly Life expectancy lost from smoking here Lung cancer risk is here Mayo clinic has calculators for melanoma MD Anderson (breast, colon , esophagus) here Melanoma: from the NCI, the risk of getting it MGH has calculators for breast, melanoma, renal Prostate cancer calculators are here Sloan Kettering has nomograms for bladder,breast, colorectal,endometrial, gastric,GIST, lung, melanoma,ovary, pancreas,prostate, renal (kidney) and sarcoma go here Fox Chases has many cancer nomograms here (for kidney, prostate, bladder, adrenal)

mskcc.org/cancer-care/adult/prostate/predictiontools

http://www.mskcc.org/cancer-care/adult/prostate/prediction-tools

PostOp Radiation…does it work? SWOG 8794 Trial path (425 men) = extraprostatic extension after surgery 10 Year PSA Cure Rate (seminal vesicle) Surgery Only Surgery Plus Radiation 12% 36% EORTC (1005 men) 5 Year Cure Rate if Positive Margins Surgery Only Surgery Plus Radiation 49% 78% German Study (Wiegel, 268 men) 5 Year Cure Rate all T3 Surgery Only Surgery Plus Radiation 54% 72%

Is it Better to Treat PostOp for High Risk Features or to Wait and Treat later if the PSA starts rising (salvage)? 8 Year Specific Survival by Group and Therapy Immediate RT Positive Margins 91% Extra-capsular Spread 92% Gleason 7 88% Node Metastases 88% Delayed 67% 75% 72% 68% Role of postoperative radiotherapy after pelvic lymphadenectomy and radical retropubic prostatectomy: a single institute experience of 415 patients Cozzarini. IJROBP 2004;59:674

Survival Benefits from PostOp Radiation for High Risk Patients RT No RT RT No RT RT No RT

PSA Cure Rates with Immediate PostOp Radiation for T3 Prostate Cancers with Undetectable PSA

NCCN Advice on PostOp Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)

Adjuvant Radiotherapy for Pathologically Advanced Prostate Cancer. A Randomized Clinical Trial. 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy. Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211). Outcome Surgery Metastatic free Survival Overall Survival 13.2 years 13.8 years 14.7 years 14.7 years Side Effects rectal complications strictures incontinence 11.9% 0% 9.5% 2.8% 23.8% 3.3% 17.8% 6.5% Ian M. Thompson, Jr, MD; Surgery + RT JAMA. 2006;296:2329-2335

NCCN Advice on PostOp Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)

Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy Lancet Oncology Volume 7, Issue 6, June 2006, Pages 472–479 Eligible patients from 36 institutes in the USA were randomly assigned in 1988–93 to receive immediate ADT (n=47) or to be observed (n=51), with ADT to be given on detection of distant metastases or symptomatic recurrences. At median follow-up of 11.9 years, men assigned immediate ADT had a significant improvement in overall survival (hazard ratio 1.84 p=0.04), prostatecancer-specific survival (4.09 p=0.0004), and progression-free survival (3.42, p<0.0001).

Is there ever a role for radiation after a man has already had his prostate removed PostOp Radiation (Adjuvant Therapy): if the pathology report from the surgery raises the concern: “was the cancer completely removed?” Salvage Radiation: if months or years after surgery the PSA blood tests starts rising again

NCCN Advice on Salvage Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)

NCCN Advice on Salvage Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)

NCCN Advice on Salvage Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)

NCCN Advice on Salvage Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron) PSADT (PSA doubling time)

NCCN Advice on Salvage Radiation RP (radical prostatectomy) RT (radiation therapy) ADT (androgen deprivation therapy e.g. Lupron)

Salvage Radiation…does it work? Depends… Original Pathology What was the Gleason? Where the surgical margins clear? Did the cancer involve the seminal vesicles or lymph nodes? Was there extra-capsular spread? How long ago was the surgery? How fast is the PSA rising (doubling time)? How high the did PSA get before deciding to try radiation? How high a dose of radiation will be used?

PSA Cure Rate after Salvage Radiation Based on Gleason Score Gleason 2-6 Gleason 7 Gleason 8-10 Time in Months

http://www.mskcc.org/cancer-care/adult/prostate/prediction-tools

http://nomograms.mskcc.org/Prostate/SalvageRadiationTherapy.aspx

http://nomograms.mskcc.org/Prostate/SalvageRadiationTherapy.aspx

Cure Rate Based on the PSA Level at the Time of the Radiation prostate-specific antigen 0.50 or less (blue), 0.51 to 1.00 (yellow), 1.01 to 1.50 (gray), and more than 1.50 ng/mL (red) J Clin Oncol. 2007 May 20;25(15):2035-41.

The Best Results are When the PSA is the Lowest Possible

Salvage (postOp) radiation works best if the PSA rise is still very low

Salvage (postOp) radiation works best if the radiation dose is high

Does Salvage Radiation Improve Survival? Mayo (2657) No improvement in 10 y mortality (70% versus 69%) Hopkins (635) Improved cancer mortality at 10 years 86% versus 62% Duke (519) All cause mortality at 11 years was reduced by 47% J Urol. 2009;182(6):2708 JAMA. 2008;299(23):2760.

Does Salvage Radiation Improve Survival? Mayo (2657) No improvement in 10 y mortality (70% versus 69%) Hopkins (635) Improved cancer mortality at 10 years 86% versus 62% Duke (519) All cause mortality at 11 years was reduced by 47% J Urol. 2009;182(6):2708 JAMA. 2008;299(23):2760.

Does Salvage Radiation Improve Survival? Mayo (2657) No improvement in 10 y mortality (70% versus 69%) Hopkins (635) Improved cancer mortality at 10 years 86% versus 62% Duke (519) All cause mortality at 11 years was reduced by 47% J Urol. 2009;182(6):2708 JAMA. 2008;299(23):2760.

Evolving Radiation Technology

CT scan is obtained at the time of the Simulation CT images are then imported into the treatment planning computer

Goal = radiation zone precisely around the prostate cancer with small margin bladder Radiation zone prostate rectum

IMRT (intensity modulated radiation therapy) using 7 different beams to target the prostate The computer can determine the optimal number of beams to deliver the radiation dose to hit the target and avoid other structures

After IMRT was established then IGRT (image guided) was introduced

Lower Risk of Side Effects with Image Guided IMRT compared to IMRT

Better Cure Rates with Image Guided IMRT compared to IMRT for Prostate Intermediate Risk High Risk

The most sophisticated technique for image guided IMRT is Tomotherapy. Combine a CT scan and linear accelerator to ultimate in targeting (IGRT) and ultimate in delivery (dynamic, helical IMRT) ability to daily adjust the beam (ART or adaptive radiotherapy)

There is significant movement of the prostate gland based on daily gas in rectum Planned target No Rectal gas Planned target, missed badly if rectal gas pushes the prostate forward Rectal gas

Using Tomotherapy to tightly target the prostate with very little radiation hitting the bladder or rectum

Typical Radiation Field for Prostate Cancer if no Surgery Has Been Performed Radiation Zone

http://www.rtog.org/CoreLab/ContouringAtlases.a spx

http://www.rtog.org/CoreLab/ContouringAtlases.a spx

The RTOG has published recommended radiation targets for patients who have had surgery and need postOp radiation (purple apex field, green seminal vesicles)

Composite MRI showing relapse sites at the anastomosis (red) or behind the bladder (green)

PostOp Radiation (after a previous radical prostatectomy) rectum bladder pubic Area of recurrence

Principles of Radiation Therapy PostProstatectomy (NCCN) • Patients with positive margins and slow PSA doubling time (>9 months) may benefit the most from PostOp radiation • In the salvage setting indications are when an undetectable PSA becomes detectable on 2 subsequent measurements, treatment is most effective if slow doubling time and PSA still less than 1 • The recommended dose is 64 to 70Gy • The target should include the prostate bed and may include the nodes, but not the whole pelvis

Side Effects of Prostate Radiation

Side Effects of Prostate Radiation rectum bladder Is related to the size and area of normal structures that are over lapped by the radiation zone…the goal is to keep the radiation zone as small as possible

Side Effects of Prostate Radiation rectum bladder With IMRT and image guided techniques the goal is to shape the radiation zone very precisely based on the pathology report and the location of the cancer, e.g. margins or seminal vesicles or lymph nodes

Side Effects of Prostate Radiation rectum bladder Radiation Zone The structures that will get hit by radiation and have inflammation or irritation: bladder, urethra and rectum

Short Term Side Effects: Irritation of bladder, urethra and rectum 1. Urinary frequency (getting up at night very few hours, take NSAID’s, or may benefit from medication) 2. Slight burning or stinging with urination (drink cranberry juice) 3. Diarrhea or more frequent, softer bowel movements, rectal soreness (take Imodium) 4. Mild skin irritation is now rarely seen 5. Fatigue is common

Long Term Side Effects: Irritation of bladder, urethra and rectum Chronic radiation cystitis or proctitis: about 6% of the men will have occasional episodes of blood in the urine or with bowel movements, this usually responds to medication (e.g. cortisone suppositories) The risk of serious damage to the bladder and rectum is now less than 1% Impotence: about 30% of men with intact prostate have problems after radiation, in men with previous prostatectomy this is even higher

Prostate Cancer Radiation after Surgery Robert Miller MD www.aboutcancer.com

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