To operate or not to operate (in young men diagnosed with TxN1M0 disease)


The appropriate treatment of younger, otherwise healthy men diagnosed with non-metastatic but lymph node-positive prostate cancer (perhaps 10 percent of all patients to be diagnosed with localized prostate cancer in America in 2014) is controversial.

Such patients would normally meet at least one of the three D’Amico criteria for high-risk disease at time of diagnosis: clinical stage T2c or higher; a PSA of > 20 ng/ml; a Gleason score of 8 to 10. But exceptions to that general rule are well known.

The available treatment options do, quite certainly, include:

  • Immediate androgen deprivation therapy (ADT) alone
  • Immediate neoadjuvant ADT + localized and wide-field radiation therapy, followed by at least 2 years of adjuvant ADT
  • Immediate radical prostatectomy with or without short-term neoadjuvant ADT and followed by
    • No additional treatment if the patient’s PSA drops to < 0.1 ng/ml and stays there (with no signs of other key risk factors)
    • Some combination of
      • Immediate wide-field external beam radiation therapy
      • Adjuvant ADT for a limited period of time
    • Salvage radiation therapy with or without adjuvant ADT if the patient’s PSA starts to rise again after initially dropping to < 0.1 ng/ml

There is no proven “right” way to treat such a patient. We have no randomized clinical trial data on which to base such decisions, and so the appropriate form of treatment for an individual patient is very much a matter of patient choice in consultation (preferably) with a really experienced, multi-specialty team that includes a surgeon, a radiation oncologist, and a medical oncologist.

Two recent, brief articles in the journal Oncology look at the pros and cons of initial surgery in the treatment of such patients.

In an article entitled “The role of radical prostatectomy and lymph node dissection in the treatment of young men with high-grade node-positive prostate cancer: there may be no RCTs — but there are good reasons to include surgery,” Kim et al. argue that the application of surgery is entirely appropriate for carefully selected patients (a position long supported by surgeons at the Mayo Clinic in Rochester, MN, who have been operating on such patients for the best part of 30 years now).

Taking an alternative view of the data, in an article entitled “The role of radical prostatectomy and lymph node dissection in the treatment of young men with high-grade node-positive prostate cancer: less is more — the benefits of surgery do not yet outweigh potential harms,” Nguyen argues that surgery in such patients is rarely (if ever) justifiable.

These articles are useful resources for patients faced with this decision (and for their advisors — whether physicians or support group leaders or other educational counselors).

The truly critical question in the selection of treatment for such men, in the view of The “New” Prostate Cancer InfoLink, is what other tests need to be done prior to reaching any decision about treatment.

Clearly risk for evident metastatic disease must be ruled out by use of both a bone scan and a CT scan. And, unarguably, the extent of the cancer is very important indeed. This suggests the need for a high quality MRI scan or PET scan that can help to determine the number and location of any positive lymph nodes and any risk for significant extension of the cancer through the prostate capsule into surrounding tissue (most particularly the bladder). Whether there is any real benefit from the use of genomic testing (Prolaris, Oncotype DX, etc.) in such patients is utterly unknown at this time.

5 Responses

  1. Treat the whole man, not just the prostate.

  2. I think like everything else right now the determination as to whether surgery is appropriate for a given patient will depend on biomarkers we have yet to identify. Some LN+ guys may respond well and some may not. But the argument that a surgical approach is definitely out is inappropriate. No science supports that argument. The fact is that many men who had positive nodes removed have fared well after RP. As we continue to find new biomarkers, translational approaches will include surgery for certain patients that have identifiable disease that is known to respond well to dissection. A clinical trial may help produce better data but alone it won’t tell us which patients will fare well and which will not. It may tell us that some fare well — but why? That is the genomic question of the day.

  3. MOST PATIENTS IN RADIATION STUDIES CITED WERE GIVEN LOWER DOSES THAN IS NOW TYPICAL

    Key studies including radiation in both articles involve time periods where radiation was normally delivered at substantially lower doses than are now used. Moreover, image-guided radiation therapy (IGRT) was likely available to few if any of these patients. The bottom line here is that radiation with current dosing levels would be expected to enjoy even better, likely substantially higher success rates than were achieved in these studies.

    Thanks again for posting these interesting articles.

  4. NEW IMAGING TECHNOLOGY EMERGING/AVAILABLE FOR ASSESSING LYMPH NODE SPREAD

    It looked like the assessment of LN+ prostate cancer in research upon which the articles were based consisted of either surgical findings or CT scan results. While these methods have notched successes, a problem with the former is that it is not comprehensive (many nodes are not removed and checked), and a problem with the latter is that it takes a pretty enlarged node before the CT scan will pick it up as likely containing cancer (smaller cancers will slip by undetected until they grow larger).

    There are now some emerging imaging technologies that offer what appears to be much higher sensitivity and specificity. One of them is the UltraSmall Superparamagnetic Iron Oxide (USPIO) Feraheme MRI scan, which has been documented at least in a poster presentation by Dr. Stephen Bravo, MD, at this time and which I believe has been accepted for publication. It is apparently capable of reliable detection of tumors of around 3 to 4 mm — much smaller than observable by CT scan, and sometimes nodes as small as 2 mm. (This is the scan I had, supplemented by an Na18F PET/CT bone scan, before deciding to undergo 39 sessions of IMRT/IGRT (TomoTherapy) last year for my challenging case diagnosed in late 1999.) Another technology is the [11C]acetate PET scan championed by Dr. Fabio Almeida, MD, in California and Arizona. A third is the [11C]choline PET/CT scan technology for which Dr. Eugene Kwon, MD has been the principal investigator at the Mayo Clinic.

    These technologies may soon radically alter the landscape of treatment for TxN1M0 disease.

  5. TREATMENT OF OLIGOMETASTATIC PROSTATE CANCER

    Oligometastatic disease, meaning disease characterized by just a few metastases (such as fewer than five bone mets in one definition) is now being treated, typically with investigational use of spot radiation to each detected met, but also with surgery.

    This could prove a beneficial approach for men with the kind of prostate cancer addressed in this article.

    There are not many papers published about this yet, but I just found these 13 papers on PubMed (using the search string: oligometastatic prostate cancer).

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