10-year outcomes of men initially diagnosed with TxN+M0 prostate cancer in the PSA era


There are relatively few “real world” data available on the 10-year survival of men with lymph-node positive but non-metastatic prostate cancer after definitive treatment for regionally localized prostate cancer in the modern (PSA) era. A study published back in April 2014 has just come to our attention that offers some insights into the long-term survival of such patients.

Rusthoven et al. used data from the Surveillance, Epidemiology, and End Results (SEER) database to examine the overall and the prostate cancer-specific survival of nearly 3,800 men with TxN+M0 prostate cancer initially diagnosed between 1995 and 2005. These men could be categorized into six groups:

  • Group A — men with pathologically proven node-positive disease (pN+ patients) who received first-line surgery (57 percent of 2991 pN+ patients)
  • Group B — men with pN+ disease who received first-line external beam radiation therapy (EBRT) (10 percent of 2991 pN+ patients)
  • Group C — men with pN+ disease who received surgery and EBRT (11 percent of 2991 pN+ patients)
  • Group D — men with pN+ disease who received no form of localized treatment (22 percent of 2991 pN+ patients)
  • Group E — men with clinical evidence of node positive disease that was not pathologically substantiated (cN+ patients) who received first-line EBRT (43 percent of 796 cN+ patients)
  • Group F — men with cN+ disease who received no form of localized treatment (57 percent of 796 cN+ patients)

The authors were then able to compare the survival rates of the patients in these six groups at 10 years, with the following results:

  • 10-year overall survival rates
    • 65 percent for men in Groups A + B + C
    • 42 percent for men in Group D
    • 45 percent for men in Group E
    • 29 percent for men in Group F
  • 10-year prostate cancer-specific survival rates
    • 78 percent for men in Groups A + B + C
    • 56 percent for men in Group D
    • 67 percent for men in Group E
    • 53 percent for men in Group F
  • Men who received localized therapy (i.e., those in Groups A + B + C +E) had better overall survival rates than men who received no localized therapy (i.e., those in Groups D + F), inclusive of men ≥70 years of age and men with ≥ 2 positive lymph nodes.
  • Among the men with pN+ disease there was no apparent evidence of differences in survival between the men in Groups A, B, or C

The authors conclude that:

In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer.

Now one does always need to be cautious about over-interpretation of data from this type of retrospective analysis, and we have only seen the abstract of this paper as opposed to the full text. It is assumed that all men who received no localized therapy did receive some form on androgen deprivation therapy (ADT), either immediately or once there was clear evidence of metastatic disease. However, it is not clear what percentage of the patients received ADT at the time of initial or adjuvant EBRT.

Having said that, it does seem very clear from these data that, for men with N+ disease at the time of diagnosis, some form of immediate localized therapy will improve long-term survival as compared to simple systemic therapy. For the men who did receive such localized therapy (i.e., those in Groups A, B, C, and E), 10-year overall survival was achieved by about 74 percent of the group compared to about 37 percent of those (in Groups D and F) who did not.

The full text of this paper would presumably provide more information related to such factors as

  • The median ages of the patients (and the age range) within the groups and across all groups
  • The use of ADT as adjuvant, initial, and salvage treatment
  • The percentage of patients in each group who went on to receive ADT after initial therapy but who did not actually die of prostate cancer

All such information would be relevant to understanding the relative merits of the different types of treatment in this cohort of nearly 3,800 patients.

It would also be interesting to see comparable data from the period from 2005 to 2010 for the same group of patients to learn whether men with similar diagnoses in the two different 5-year time frames had different rates of overall and prostate cancer-specific survival at 10 years of follow-up.

7 Responses

  1. The problem is that two studies (Abdollah and Rusthoven) found a benefit to salvage RT in men with pN+ status, while one study (Kaplan) found no benefit. (This was briefly mentioned in setting “C” in an earlier commentary This will be determined by RTOG 0534 for the case where positive LNs are suspected, but not identified (setting “D” in the above article).

    Among patients seeking first-line treatment for cN+ the data are less equivocal, as discussed in the above-cited article (setting “A”). Still, as always, there are many open questions.

  2. I believe that there is enough evidence that men with clinical N0 disease who are pN+ at surgery should have their surgery completed. Aborting surgery does a disservice to these men and shortens their life. Retrospective though the evidence may be (Messing notwithstanding) good surgical practice should change more quickly to this newer standard.

  3. Hmmm … Well I think that is probably a fair comment for men with just a few +ve nodes. However, there are still relatively rare cases, even today, of men with unexpectedly high numbers of positive lymph nodes for whom completion of the surgery would come with risk for high levels of lymnphedema and related side effects, so I suspect that surgeons need some leeway to be able to make good medical judgement in such cases.

  4. Hmmm … Well I think that is probably a fair comment for men with just a few +ve nodes. However, there are still relatively rare cases, even today, of men with unexpectedly high numbers of positive lymph nodes for whom completion of the surgery would come with risk for high levels of lymnphedema and related side effects, so I suspect that surgeons need some leeway to be able to make good medical judgement in such cases.

  5. Strong Probability of Selection Bias Seriously Impacting These Results

    Thank you for posting this, as it is certainly food for thought.

    Selection bias is likely to be responsible for the much lower 10-year overall and prostate cancer survival figures for group F, as well as for the lower survival figures at 10 years for groups D and E compared to the combined figures for groups A, B, and C. That was definitely true for me, facing my own life-threatening case back in 1999. I, knowing little about the disease beyond the raw odds in materials from the American Cancer Society, chose surgery, which would have almost certainly been ineffective and burdensome. Fortunately, I was rejected by Johns Hopkins, though Hopkins did accept me for radiation. Again fortunately, while preparing for radiation I concluded that the chances for success with then-existing technology there were low, as Hopkins had advised, while ADT in expert hands offered some hope. It is likely that patients with life-threatening cases were steered away from surgery by many doctors, and even from radiation. Because of the more challenging and potentially lethal case characteristics, more of these patients were not alive at 10 years.

    Another factor at work is that radiation therapy — both EBRT and brachytherapy — was clearly substandard at many institutions during much of the 1995-2005 period. The big problems with EBRT were inadequate dosing and targeting the cancer while sufficiently lowering doses to healthy tissues. The big problem for brachy was cold spots that were not detected and effectively retreated. Radiation and associated technologies (such as imaging, androgen deprivation therapy, etc.) have improved enormously since the time period in the study, so much so that this study is mainly of historical interest as far as radiation and ADT are concerned. (Sophisticated ADT was then available, but, then as now, many doctors are not savvy in its use. I am convinced that a great proportion of my peers on ADT have received a sub-optimal form of that therapy.)

    As to the benefit of local therapy for N+ disease, Dr. Horst Zincke of the Mayo Clinic researched this for years, with some of his papers indicating a benefit. He was known for combining surgery with ADT.

    All this said, I believe that the following statement by Sitemaster is probably true: “… Having said that, it does seem very clear from these data that, for men with N+ disease at the time of diagnosis, some form of immediate localized therapy will improve long-term survival as compared to simple systemic therapy.” I believe that is more true in the present, with much improved forms of radiation and ADT available, as well as effective surgery, especially now for all therapies that we know how to spot nodes and other metastases that are cancerous at the vast majority of likely sites, not just those in nodes that are easily accessible to the surgeon, or visible on imaging that can catch only large mets, as in the past. Moreover, we are now in position to attack those mets in many instances.

  6. Trying to Better Understand Who Survives Prostate Cancer Today

    I’m interested in this line of thought because I’m trying to figure out how much node-positive disease pulls down relative survival at 10 years, which is 99% per current data from the American Cancer Society (ACS). I suspect the answer is that there are proportionately few node-positive cases these days, just as there are proportionately very few men diagnosed with metastatic disease. Here’s what’s on my mind.

    I suspect that those of us who staff tables about prostate cancer at health fairs often present the current “relative” survival statistics for prostate cancer from the American Cancer Society (ACS):

    — almost 100% at 5 years
    — 99% at 10 years
    — 94% at 15 years
    — and, for men diagnosed with distant metastases, only 28% at 5 years (which sure underscores an advantage for screening!)

    So how do these numbers relate to the considerably lower numbers in this study? One large difference is that the ACS numbers are for “relative” survival, which means how many men survive compared to their age peers who do not have the disease. For instance, that non-relative (absolute) percentage surviving at 15 years is a lot lower than 94% if you do not divide it by the number of age peers then surviving. Put another way, a lot of our age peers will not have survived by then either.

    Another difference is that the figures in the study above are for the period 1995-2005, while the ACS figures are much more current. The ACS advises, “Keep in mind that just as 5-year survival rates are based on patients diagnosed and first treated more than 5 years ago, 10-year survival rates are based on patients diagnosed more than 10 years ago (and 15-year survival rates are based on patients diagnosed at least 15 years ago).” Therefore, while the ACS number for 10-year survival is for men treated at the most recent from 2015 minus 10 years, which is 2005, to not earlier than 2001 (which would be the year before 15 years back), this study clearly involved many men treated in the earlier period from 1995 to 2000. (That’s clear because the entire study period spanned 1995 to 2000.)

    A third difference is that the 5-, 10-, and 15-year survival figures for all patients include those with metastatic disease at diagnosis, while the figures in the study exclude men with metastatic disease (“M0”). One inference from the ACS data is that very few men today are diagnosed with metastatic disease, as, otherwise, the 5-year survival number would not be nearly 100%. (In other words, those with metastatic disease at diagnosis, with their 28% relative survival at 5 years, would pull down that 100% figure if they were numerous, so they cannot be numerous.

    Any thoughts?

  7. Dear Jim:

    (1) I think that you are just confusing people. All this paper is saying is that if you get diagnosed with N+M0 disease, you are probably wise to have some form of immediate localized therapy (possibly along with adjuvant treatment as well). This is something you appear to agree with.

    (2) In the past week alone I have dealt with two patients newly and initially diagnosed with metastatic disease; another man diagnosed with what is almost certainly N+ and potentially micrometastatic disease, and two others diagnosed with Gleason 8-10 disease who are at significant risk for pN+ disease. I think you are vastly underestimating the numbers of men who still get diagnosed today with N+ and M1 disease. Just because the numbers of men getting diagnosed each year with low-risk disease has gone up massively in the past 25 years doesn’t for one moment mean that the numbers of men getting diagnosed with N+ and M1 disease have dropped to anything approaching negligible levels.

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