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Thread: Post-op RT in Localized Prostate Cancer: When, How Much, and How Fast?

  1. #1

    Post-op RT in Localized Prostate Cancer: When, How Much, and How Fast?

    I added this article to the Subforum today, Topic (K). I found this "split decision" statistic of interest.

    Postoperative Radiation Therapy in Localized Prostate Cancer: When, How Much, and How Fast? [2019, Full Text]

    Radical prostatectomy is one of the most commonly recommended definitive options for management of patients with localized prostate adenocarcinoma. Unfortunately, biochemical relapse is common after radical prostatectomy, especially in patients with high-risk features: extracapsular extension, seminal vesicle invasion, or positive margins. The consensus guidelines of the American Urological Association and American Society for Radiation Oncology (1) and the European Association of Urology (2) recommend physician-initiated, multidisciplinary discussions of the risks and benefits of postprostatectomy radiation therapy (RT) for patients with adverse pathologic features and/or evidence of persistent or rising prostate-specific antigen (PSA) levels. However, there is a dramatic polarization among North American genitourinary (GU) radiation oncology experts on the issue of timing of postprostatectomy RT, with an almost 50/50 split in endorsement of adjuvant RT in patients with high-risk features versus initial close clinical and laboratory surveillance with initiation of early salvage RT at the time of biochemical failure (3).
    ...
    [Emphasis mine]

    We've seen this split reflected in the advice forum Brothers are getting from consultations with ROs. I think genomics (e.g., the Decipher test) is making a contribution to decision-making regarding ADT vs SRT.

    We need prospective clinical trials with evenly matched arms, so we know, given a set of adverse findings and/or post-op PSA values and trend, when to treat. In other words, how to reduce overtreatment as much as we can but still take advantage of starting treatment early when it is demonstrated to be advantageous.
    Last edited by DjinTonic; 01-15-2019 at 07:04 PM.
    69 yr at Dx, BPH x 20 yr, 9 (!) negative biopsies, PCA3 -
    2013 TURP (90→30 g) then PSA 2x/yr, DRE yearly
    6-06-17 DRE nodule R, last PSA rise, on finasteride: 3.6→4.3
    6-28-17 Biopsy #10: 2/14 cores: G10 (5+5) 50% RB, G9 (4+5) 5% RLM
    Bone scan, CTs, X-rays: negative
    8-7-17 Open RP, neg. frozen sections, Duke Regional, my Uro, 8-20 RPs/mo. x 25 yr.
    SM EPE LVI SVI LNI(16): negative, PNI+, nerves spared
    pT2c pN0, bilat. adenocarcinoma G9 (4+5) 5% of prostate (4.5 x 5 x 4 cm, 64 g)
    11-10-17 Decipher 0.37 Low Risk: 5-yr met risk 2.4%; 10-yr PCa-specific mortality 3.3%
    Dry; ED OK with sildenafil
    9-16-17 (5 weeks) PSA <0.1; Pomi-T (2 cap/day)
    LabCorp uPSA (Roche ECLIA):
    11-28-17 (3 mo. ) 0.010
    02-26-18 (6 mo. ) 0.009
    05-30-18 (9 mo. ) 0.007
    08-27-18 (1 year) 0.018
    09-26-18 (13 mo) 0.013 (checking rise)
    11-26-18 (15 mo) 0.012

  2. #2
    Top User garyi's Avatar
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    Fine observations, Jared, and much needed RCT's. Of course, we are dealing with RO's livelihoods
    72...LUTS for the past 7 years
    TURP 2/16,
    G3+4 discovered
    3T MRI 5/16
    MRI fusion guided biopsy 6/16
    14 cores; four G 3+3, one G3+4,
    CIPRO antibiotic = C. Diff infection 7/16
    Cured with Vanco for 14 days
    Second 3T MRI 1/17
    Worsened bulging of posterior capsule
    Oncotype DX GPS 3/17, LFP risk 63%, Likelihood of Low
    Grade Disease 81%, Likelihood of Organ Confined 80%
    RALP 7/13/17 Dr. Gonzaglo @ Univ of Miami
    G3+4 Confirmed, Organ confined
    pT2c pNO pMn/a Grade 2
    PSA 0.32 to .54 over 3 months
    DCFPyl PET & ercMRI Scans - 11/17
    A one inch tumor remains in prostate bed = failed surgery
    All met scans clear
    SRT, 2ADT, IMGT 70.2 Gys @1.8 per, completed 5/18
    PSA <.006 9/18, .054 11/18, .070 12/18, .067 2/19
    We'll see....what is not known dwarfs what is thought to be fact

  3. #3
    (See my next post below)
    Last edited by DjinTonic; 01-15-2019 at 09:08 PM.

  4. #4
    Quote Originally Posted by DjinTonic View Post
    I changed the url in the article link above so folks can see the full text, but I get it only on my PC and not on my tablet.
    Hi Dj! I still get "linked" to the image of Page 1 of the paper. I tried to download the full PDF but this requires an ASTRO membership.

    I am particularly interested in (red): "Post-op RT in Localized Prostate Cancer: When, How Much, and How Fast?"

    Let us know!

    TY!

    MF

  5. #5
    Quote Originally Posted by Michael F View Post
    Hi Dj! I still get "linked" to the image of Page 1 of the paper. I tried to download the full PDF but this requires an ASTRO membership.

    I am particularly interested in (red): "Post-op RT in Localized Prostate Cancer: When, How Much, and How Fast?"

    Let us know!

    TY!

    MF
    This is an introduction to summaries of four separate studies, each commented, followed by 31 references. Unfortunately only the introduction is free.


    Hwang et al. Comparison between adjuvant and early salvage postprostatectomy radiotherapy for prostate cancer with adverse pathological features. JAMA Oncol 2018.

    Ghadjar et al. Impact of dose intensified salvage radiation therapy on urinary continence recovery after radical prostatectomy: Results of the randomized trial SAKK 09/10. Radiother Oncol 2018.

    Picardi et al. Hypofractionated radiotherapy for prostate cancer in the postoperative setting: What is the evidence so far? Cancer Treat Rev 2018.

    Siepe et al. Postoperative hypofractionated radiation therapy in prostate carcinoma: A systematic review. Anticancer Res 2018.



    From the Full-Text comments:

    The results of 3 randomized clinical trials [...] are eagerly awaited. Until then, patients with high-risk features should be evaluated by radiation oncologists after the first postoperative PSA level is determined and should be offered 2 options--adjuvant RT versus frequent PSA monitoring with early salvage RT at the time of biochemical recurrenced--with a clear understanding that adjuvant RT is likely to overtreat a substantial proportion of patients with no clear evidence at this time of its ability to decrease the rate of development of distant metastases and improve OS.
    [Emphasis mine. OS = overall survival]
    Last edited by DjinTonic; 01-15-2019 at 10:04 PM.

  6. #6
    TY Dj! The authors have published a summary overview of 3 Trials. They do NOT identify the PSA level at which SRT should commence; although it is after BR is reached. Guessing we can assume a PSA level of at least 0.2 ng/ml.

    The question to which we seek correct answers is: For those who opt for early SRT at very low clinically undetectable uPSA levels, how many might never have progressed to significant recurrent disease? Very difficult to speculate! But likely for some, SRT was unnecessary.

    MF
    Last edited by Michael F; 01-16-2019 at 03:32 PM. Reason: ,

  7. #7
    Quote Originally Posted by Michael F View Post
    TY Dj! The authors have published a summary overview of 3 Trials. They do NOT identify the PSA level at which SRT should commence; although it is after BR is reached. Guessing we can assume a PSA level of at least 0.2 ng/ml.

    The question to which we seek correct answers is: For those who opt for early SRT at very low clinically undetectable uPSA levels, how many might never have progressed to significant recurrent disease? Very difficult to speculate! But likely for some SRT was unnecessary.

    MF
    Mike, see the above take-home message I posted above yours. Note their emphasis on both over-treatment and possibly no OS benefit for adjuvant RT. Perhaps the three studies whose results are awaited will also shed some light on the criteria for determining when to begin SRT.

    We also know that at 0.2, or even 0.4, a good portion of men with BCR will not go on to clinically recurrence. Unfortunately, at the time of BCR, we don't have a way of knowing which men.
    Last edited by DjinTonic; 01-15-2019 at 10:28 PM.

  8. #8
    Top User garyi's Avatar
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    Quote Originally Posted by Michael F View Post
    TY Dj! The authors have published a summary overview of 3 Trials. They do NOT identify the PSA level at which SRT should commence; although it is after BR is reached. Guessing we can assume a PSA level of at least 0.2 ng/ml.

    The question to which we seek correct answers is: For those who opt for early SRT at very low clinically undetectable uPSA levels, how many might never have progressed to significant recurrent disease? Very difficult to speculate! But likely for some SRT was unnecessary.

    MF
    They don't know, Michael, and maybe never will. A lot of surgeries, RT and SRT are surely unnecessary. So many with so called BCR, at very low PSA, get scared into premature treatment, IMHO. Expecting medical researchers to be excited about possibly putting many of their fellow physicians out of much of their lifetime studied work, has to be tough. Yes, I'm cynical.

    It sucks!
    72...LUTS for the past 7 years
    TURP 2/16,
    G3+4 discovered
    3T MRI 5/16
    MRI fusion guided biopsy 6/16
    14 cores; four G 3+3, one G3+4,
    CIPRO antibiotic = C. Diff infection 7/16
    Cured with Vanco for 14 days
    Second 3T MRI 1/17
    Worsened bulging of posterior capsule
    Oncotype DX GPS 3/17, LFP risk 63%, Likelihood of Low
    Grade Disease 81%, Likelihood of Organ Confined 80%
    RALP 7/13/17 Dr. Gonzaglo @ Univ of Miami
    G3+4 Confirmed, Organ confined
    pT2c pNO pMn/a Grade 2
    PSA 0.32 to .54 over 3 months
    DCFPyl PET & ercMRI Scans - 11/17
    A one inch tumor remains in prostate bed = failed surgery
    All met scans clear
    SRT, 2ADT, IMGT 70.2 Gys @1.8 per, completed 5/18
    PSA <.006 9/18, .054 11/18, .070 12/18, .067 2/19
    We'll see....what is not known dwarfs what is thought to be fact

  9. #9
    Top User
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    Is there a study that defines the overtreatment concern? Do we really know?

  10. #10
    Quote Originally Posted by Another View Post
    Is there a study that defines the overtreatment concern? Do we really know?
    A partial answer (copied from a post I made elsewhere):

    A 2013 study, published in Molecular and Clinical Oncology, followed 200 RP patients for a median of 52-months to monitor their µPSA values and post surgery progression toward biochemical recurrence (BCR), which was defined as two consecutive PSA tests with a value > 0.2 ng/ml.

    94% of the patients (183) with a PSA nadir of < 0.008 had not experienced BCR at a median followup time of 52-months.

    Sixtysix (66) of those patients who reached a nadir of <0.008 subsequently progressed to have a PSA > 0.008 4+ year followup.

    Thirtythree (33) of those 66 patients never exceeded a PSA value of 0.05 in the 52-month followup. That means almost 52% of the patients whose PSA value rose above the 0.008 nadir never exceeded 0.05, which is only 1/4 of the definition of BCR. The author's characterized those 33-patients as having a PSA transition pattern of "peaking out." Their pathology characteristics are not real great. 46% of them were T3 or greater, 30% were G8 or greater, and 21% had positive surgical margins.


    That says to me that we can start with a very low PSA value post surgery and show some significant increase in the PSA values while not coming close to BCR (PSA > 0.2 twice) in over 4-years.

    I have read some other studies looking at progression toward BCR but have not yet found them. Your question is always in the forefront of my PCa thoughts!
    DOB: July 1947
    PSA: 2.0/2004 4.0/2010 5.8/2010 4.5/2012 5.6/2013 Normal DRE each year
    5/18 PSA: 9.2
    6/18 PSA: 10.2 & 8.4% Free
    DRE small soft prostate w/no abnormalities
    6/28 3T mpMRI PIRADS 3
    18 cc gland=PSD 0.57 ng/cc
    0.32 cc lesion in apical PZ with subtle T2 signal hypointensity
    mild restricted diffusion of contrast into lesion
    remainder of prostate unremarkable intact capsule
    7/18 4KScore 34% Probability Gleason =>7

    8/03/18 Bx: Adenocarcinoma 6 of 13 cores ONLY L lobe
    T1c / Grade II / unfavorable intermediate
    extent of G3-G4 tissue far greater than indicated by MRI
    G6 (3+3) 70% LL Base 50% L Lateral Mid 20% L Base
    G7 (3 +4) 100% LL Apex 20% L Mid 60% L Apex
    8/15/18 Clear CT scan and Bone Scan
    RALP 8/23/18 pT3a, G7 (3+4), 20% involvement, SM+ (Focal 2mm G6), EPE(Focal G6)+, PNI+, LNI-, SVI-, LVI-
    7g Tumor 20x size in MRI & biopsy report & in BOTH lobes not just L as biopsy reported

    PSA Post Surgery
    10/3/18 0.021
    01/4/19 0.018

 

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