Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial

Volume 12, Issue 5, May 2011, Pages 451-459

Conclusion: 6 months of neoadjuvant androgen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer, particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged androgen deprivation.

This trial showed 6 months better than 3 months ADT

Notes: They allowed pts with PSA = 203.9 ng / ml into the trial…

Someone could look into the PR 07 trial , the highest PSA level enrolled in the study.

Recently i m not sure whether you guys are aware there was the practice changing results of a trial called PR07 trial reported in last years ASCO.

http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=49170

And giving radiotherapy in addition to hormone therapy improves survival for men with locally advanced prostate cancer.

http://www.ctu.mrc.ac.uk/news_and_press_releases/news_archive/pr07_interim_analysis_010710.aspx

Get his PSA re-checked from a different lab AFTER making sure that there has been no "digital manipulation" of his prostate before we jump to conclusions.

I think it would be a worthwhile trial.

If not, then the case is HIGH RISK and should be treated with the intent of cure with neoadjuvant hormones, primary radiotherapy and adjuvant hormones (probably lifetime).

If you think it is, then I'd like to be informed of the system as I haven't seen it published.

Even if you believe his metastatic rate is 100%, the local radiotherapy will mean that local failure is very very unlikely, so local treatment is not wasted. Hormones alone will see local failure in 5-7 years (what I call the "Trial of Death" approach!)

There has been some recent update which estimates this benefit at 6.4% at 7 year Follow up (published in 2010 or 2011)

The Std Chemo regimen internationally practised is usually Cisplatin 75 mg/m2 D1, Gemcitabine 1 g / m2 D1, 8 , 15 [ 28 day cycle ]

The only major problem is this should be offered to patients who are fit and well with KPS >70%, with adequate renal function.

MVAC and CMV chemo are now considered out of date as there is clear evidence of increased toxicity compared with Cis / Gem (at least in the mets setting… direct randomised data).
But for discussion purpose, all these regimens are equivalent wrt local control and overall survival.

1. Include entire gross disease at the time of presentation.
2. Margin of 2 cm respecting anatomical boundaries ok
3. Gorss nodes needs to be included
4. No need for prophylactic irrradiation

Constaints are not very well defined even for the adult patients - however as this study shows that underdosing carries a more severe risk of failure - I would concentrate more on getting the coverage and dose correct rather than thinking about normal organ constraints. Testicular shielding can be implemented but rest of the organs especially small bowel and rectum will get treated. Bladder I would not consider sparing at all.

Bones again are difficult point doses of 25 -35 Gy can be suggested as a cutoff but since you say the initial tumor was large it would be exceptionally difficult to achieve. As it is without surgery this patient is not receiving the optimal treatment. I found this reference where they modelled the effects of RT on bone growth
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T7X-4G0HV9J-3&_user=7895621&_coverDate=08%2F01%2F2005&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_rerunOrigin=scholar.google&_acct=C000073114&_version=1&_urlVersion=0&_userid=7895621&md5=9b7dc2b6e489447aa54ff3ffb3437938&searchtype=a

http://www.ncbi.nlm.nih.gov/pubmed?term=International%20Phase%20III%20Trial%20Assessing%20Neoadjuvant%20Cisplatin%2C%20Methotrexate%2C%20and%20Vinblastine%20Chemotherapy%20for%20Muscle-Invasive%20Bladder%20Cancer%3A%20Long-Term%20Results%20of%20the%20BA06%2030894%20Trial

Your concepts are absolutely clear, ideally you would prefer B/l pelvic LND… but i agree with logistic reasons you cant offer ideal treatments.
I m sure you would have requested a staging scan CT chest + Abdo + Pelvis and asked for Alk Phosphatase (and asked for Bone scan if elevated and / or pt symptomatic).

There is certainly a role of RT. Intent = Radical
You are absolutely right about the areas at risk …
CTV = B/L inguinofemoral + Pelvic LN.

Pelvis can take upto 45-50.4 Gy @ 1.8Gy / #

PNE is certainly an indication for Boost and you can use a Ant electron Field Boost in fact to both groins (10 Gy)

The right groin can be spared of a boost if HPR mentions a focal area ONLY of PNE.

Biggest concern at time of consent = Risk of Lymphedema … wonder what figure would you quote Nilesh ?

This gentleman is at risk of distant mets as well, and some groups/clinicans do offer additional adjuvant chemo.. But of course there is no good evidence for this approach, and hence for the purpose of our discussion we can ignore it for the time being.

Stage pT1pN2

Ideally his bilteral pelvic LND should have been done.
Not possible now for logistics reasons.

Role of RT i believe is to prevent LN relapse. Hence I need to treat bilateral Inguinofemoral and pelvic LN to a dose of 50-60 Gy (60 Gy for lt groin)

I need opinion of house

We don't have randomized evidence for the admission of doses beyong the range of 64-66 Gy. There are several retrospective reports showing better effeciency with higher doses

Bias is an issue with such reports:
If you have a patient with clear positive margins and with a PSA persisting & rising after operation, the chance that the cause for the rising PSA is clearly in the prostatic fossa.
However if you have a patient with a PSA recurrence a couple of years afte R0-prostatectomy, then it's less clearer is the problem is local. He could also have a recurrence in lymph nodes or distant metastasis.
We don't know, if the colleagues which published their results with dose escalation, escalated the dose in patients where local recurrency was more probable than in those with less dose.

Raising the local dose to a high level can lead to late toxicity, including urethral stenosis, etc. I would be careful.