After Radical Prostatectomy - Gleason 4+5

Time for me to get some feedback on difficult personal treatment decisions. I am a 70 year old semi retired physician. 4 years ago I had an asymptomatic stage 4 non hodgins lymphoma diagnosed on a random MRI of my spine. Pathology suggested a poorly curable type (margin cell) but after rCHOPP, I am now recurrence free. My younger brother developed prostate cancer this year and I said "what the hell" its been several years since I was checked (primary care doctors no longer do rectal exams) and I went to a urologist friend. Worrisome nodule was noted, PSA 9.8, and MRI found PIRADS 4 -1 cm nodule and nothing else. Bone scan negative. I just had a normal PET for my lymphoma follow up. Prostate Biopsy showed 10/12 positive for adenocarcinoma - 2=4+5 and others 4+3 or 3+3 . Ouch!! My brother had a very very difficult time with seed and EBRT. I chose robotic assisted radical prostatectomy. Path showed Adenocarcinoma 80% gleason 4 and 20% gleason 5 involving both lobes of prostate and both seminal vesicles, perineural invasion, but all surgical margins free (T3bN0R0). Now 4 weeks post op and incontinence is a pain but hopefully will get better.

I have reviewed most studies that I have access to. I go back to my surgeon next week and I guess I will get my first post op PSA. I think he is in favor of frequent monitoring Ultrasensitive PSA and rapid salvage therapy. Much of the literature recommends adjuvant treatment - EBRT +/- Hormonal. Radiation treatment early post op may cause serious voiding complications and Hormonal treatment is what it is. I hate to leave behind early treatable cancer. The data shows disease free survival is improved to a modest extent but at what side effect and lifestyle cost?

Love to hear your perspectives.

Thanks

Dr. V

Hi Dr. V and Welcome to the Forum!

Recent trials designed specifically to look at adjuvant vs. early salvage after RP with adverse path findings seem to indicate many men can be spared overtreatment by waiting to see if there is a PSA rise and opting for salvage therapy if needed. However I do not think this applies to high- and very-high risk men. I suggest you have a look at papers in the past 5 years by Dr. Anthony D'Amico, the well-known radiologist, who has studied the adjuvant-treatment issue for G9-10 men. He still believes that G9-10 men with even one major post-RP adverse finding (EPE+, LN+, SM+, SVI+) should be presented with the adjuvant option and be told that adjuvant therapy is needed to complete primary treatment. We G9-10 men are a minority of cases in studies, which is why I find Dr. D'Amico's work precious.

I was very fortunate to have had a p2T N0 R0 outcome after RP for G9 (4+5), a low-risk Decipher result, and only 5% cancer burden. I had no further treatment (so far). After reading a study by Dr. D'Amico, I asked my uro/surgeon what he would have recommended if my path report had found only lymphovascular invation --the one adverse finding that Dr. D'Amico did not include in his list of adverse findings (PNI+ really doesn't count). My doc said he'd have advised I see an RO for adjuvant RT. Note that all adjuvant is generally done after a some healing period after surgery.

If your first PSA (and confirmation) shows persistent PSA (1.0 or higher), the decision will be made for you, as that is usually determinative for adjuvant therapy. If your PSA is <0.1 and you intend to base a treatment decision wholly or partly on your PSA and your PSA trend, I very strongly suggest you track your PSA with Labcorp's 3-decimal ultrasensitive PSA test.

The name of the game, as I'm sure you know, is preventing metastatic disease. (You did not mention it, so I assume you did not have EPE--you would still be pT3b). It is possible that all your PCa was removed with your prostate and seminal vesicles. What was your tumor burden (percentage of the prostate involved)? I would choose adjuvant given the SVI+. If you are serious about very early salvage, I would get the Decipher RP test as Mumbo suggests. If it doesn't come back low-risk for mets, that would be another factor to put in the Adjuvant column.

(If you have the Decipher RP test, be sure to request the optional GRID report, which is not validated for clinical decision-making, but has much interesting info, including how your PCa theoretically responds to RT.)

Assuming no persistent PSA, you may find that your PSA starts to creep up during your first months of healing, which would lead you to adjuvant anyway--but I hope not.

Please let us know how you are doing. My hunch is that you'll have more info coming you way to help you decide: your continence progress, initial PSA, PSA trend, Decipher results, your own research, your docs' opinions (and any consults), etc.

All the best!

A few questions:

What was your pre-op PSA?
How many lymph nodes were removed?
Did they find EPE or lymphovascular invasion?
Any (intra)ductal PCa or cribriform pattern identified?
Does your path report have the percentage of prostate involved by the PCa?

Djin

Dr V. Nothing I can add to the excellent advice you’ve received above. Other than to emphasize that you should try to give yourself as much time as is safely possible to heal before starting ART.

Welcome to the forum.

Welcome, Dr. V.

Well, you've got a rough diagnosis. Here's what the general understanding among us non experts here about post surgical PSA:
The 6 week PSA is pretty commonly done, but it is not definitive. The 3 month (12 week) is usually the one to determine if Adjuvant therapy is needed. Also, the longer you wait after surgery to start radiation, the better your side effect profile is likely to be.

What you hope for is a significant drop at 6 weeks--hopefully down to 0.1 or lower. At 3 months, you want to be undetectable on the high sensitivity test. If you are, then you keep doing PSA tests regularly--probably every 3 months for at least a year.

Hang in there....keep coming around.

My experience suggests the importance of waiting to heal before initiating RT. Ten months after RP I was fully continent. RT a few months later stated me leaking again, and still four years later I leak if I drink alcohol. (Unintended benefit is that I drink much less than before.) I expect that the incontinence would be worse if I had started the RT sooner.

Dr.V - Not the best news, it would be nice to have a non-detectable post-op PSA but another point or two will make that part clear. Little surprised you would get a PSMA scan so quickly without another PSA test.

Other that that, how is your recovery coming? Feeling better physically? Is your continence coming along on schedule?

Yes, the current news is hard to swallow and is hard on wife and family but take it slow until you get another PSA test and some scans under your belt. Hopefully, some better news is just around the corner.

What recommendations do people have concerning their therapy with androgen blockers,either oral or injectable, short term pending EBRT or longer term? Differences in side effects?

Well I never: live and learn https://pubmed.ncbi.nlm.nih.gov/23906190/ Good luck Dr. V and I hope you get the urinary issues sorted: that all seems a poor reward for a brave and IMO correct step. Do tinker with those nomograms: they put in numbers the true reward for getting these treatments.

ADD A bit of a rant: sorry. But really, what's wrong with these lunatic surgeons? (Japanese in this case in the above pub.). Getting almost 10% urinary leakage, a serious complication, and enough retention to warrant his own RCT and STILL pulling caths after 5 days./ADD

This recent Italian study may be of interest:

Predictors of Patient-Reported Incontinence at Adjuvant/Salvage Radiotherapy after Prostatectomy: Impact of Time between Surgery and Radiotherapy (2021, Full Text)

"Abstract
Background: Baseline urinary incontinence (UI) strongly modulates UI recovery after adjuvant/salvage radiotherapy (ART/SRT), inducing clinicians to postpone it “as much as possible”, maximizing UI recovery but possibly reducing efficacy. This series aims to analyze the trend of UI recovery and its predictors at radiotherapy start. Methods: A population of 408 patients treated with ART/SRT enrolled in a cohort study (ClinicalTrials.gov #NCT02803086) aimed at developing predictive models of radiation-induced toxicities. Self-reported UI and personality traits, evaluated by means of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) and Eysenck Personality Questionnaire - Revised (EPQ-R) questionnaires, were assessed at ART/SRT start. Several endpoints based on baseline ICIQ-SF were investigated: frequency and amount of urine loss (ICIQ3 and ICIQ4, respectively), “objective” UI (ICIQ3 + 4), “subjective” UI (ICIQ5), and “TOTAL” UI (ICIQ3 +4 + 5). The relationship between each endpoint and time from prostatectomy to radiotherapy (TTRT) was investigated. The association between clinical and personality variables and each endpoint was tested by uni- and multivariable logistic regression. Results: TTRT was the strongest predictor for all endpoints (p-values ≤ 0.001); all scores improved between 4 and 8 months after prostatectomy, without any additional long-term recovery. Neuroticism independently predicted subjective UI, TOTAL UI, and daily frequency. Conclusions: Early UI recovery mostly depends on TTRT with no further improvement after 8 months from prostatectomy. Higher levels of neuroticism may overestimate UI."

(See Full Text)

Djin

Dr. V,
I was 50 when diagnosed with 4+5 followed by RALP. Like you, I had persistent PSA after only 3 months post-surgery. I waited about 10 months before beginning SRT / ADT. For me, both the SRT and ADT were uneventful in terms of side-effects. I feared the worst — especially for the ADT — but my fears were unfounded. For me, it all worked out fine. Lucky? Perhaps, but please know there IS hope. Hang in there — I wish you the best.