The management of recurrent prostate cancer after first-line therapy

Traditionally, men with prostate cancer who had recurrent disease after first-line surgery or first-line radiation therapy had a limited number of treatment options, but we are now seeing a significant expansion in the range of options available (although limited data are as yet available to support the effectiveness of nearly all these options).

Newer options for second-line (“salvage”) treatment of men with a rising PSA after first-line therapy now appear to include at least some and perhaps all of the following:

  • External beam radiation therapy (EBRT) of various types in men initially treated with brachytherapy, cryotherapy, and high-intensity focused ultrasound (HIFU)
  • Brachytherapy in men initially treated with surgery,  EBRT, and HIFU
  • HIFU in men initially treated with surgery, brachytherapy, and EBRT
  • Cryotherapy in men treated with surgery, brachytherapy, and EBRT

To these we can of course add the more traditional options of

  • A second HIFU treatment after first-line HIFU
  • Salvage surgery after EBRT, brachytherapy, cryotherapy, and HIFU
  • Salvage EBRT after surgery and HIFU
  • Androgen deprivation therapy (ADT or hormonal therapy), which is never curative on its own, after just about anything.

We have no intention of trying to provide a detailed review of the pros and cons of all of the available options. For starters, we doubt that sufficiently good data are available to be able to offer a really useful review of all of the options. Rather, our goal is to merely make men aware that these options do, in fact, exist, although the information on quality of patient outcomes needs to be very carefully considered in coming to any conclusions about the relative merits of each individual option.

We have, for example, commented within the past few months on data from an experienced HIFU team about their outcomes using second-line HIFU in men with a rising PSA after first-line EBRT.

We have also noted two other recent papers/presentations that also seem to be of some interest.

Gomez-Veiga et al. have discussed experience of using salvage brachytherapy in men with biochemical progression after EBRT and after surgery. According to this review:

  • 5-year biochemical progression-free survival (bPFS) rates following salvage brachytherapy in men after EBRT are of the order of 20-87 percent.
  • One study has reported a 10-year bPFS rate of 54 percent from the use of salvage brachytherapy after first-line EBRT.
  • In men receiving salvage brachytherapy for radical prostatectomy failure, reported bPFS rates range from 25.8 percent at a median follow-up of of 29 months to 70 percent at a median follow-up of 20 months.
  • A recent Spanish study of the use of salvage brachytherapy in a series of 42 patients with failure following radical prostatectomy shows
    • A 5-year bPFS rate of 88.6 percent
    • A prostate cancer-specific survival rate of 97 percent
    • Relatively low complication rates

Gomez-Veiga et al. state that “Optimization of salvage brachytherapy is under way and involves accurate placement of seeds, dose optimization and optimal patient selection.” There would appear to be little doubt that — for some carefully selected patients — salvage brachytherapy may be an appropiate option, but we need a great deal more data to rellly validate this option.

In a presentation at the European Association for Urology meeting just the other day (as reported on the Medscape web site), Barentz gave a report on a very small number of men treated with multiparametric MRI-guided cryotherapy as a salvage treatment after failure of EBRT.

Dr. Barentz is clearly enthused by the potential of multiparametric MRI-guided cryotherapy, not only as a salvage therapy for radiation failure but also as a first-line form of treatment. However, the number of patients treated to date with salvage MRI-guided cryotherapy is small (n = 9); the follow-up is very short (5 men have been followed for just 3 months so far); and (again) we are going to need to see a lot more data before one could look seriously at this type of cryotherapy as becoming a “standard” form of treatment that might be used in the salvage setting (or as a first-line therapy).

A statement made by Dr. Barentz is somewhat concerning to us. According to the Medscape report, Dr, Barentz is quoted as follows:

Whenever you have a negative TRUS biopsy, you need to conduct [a multiparametric] MRI and then a more targeted biopsy. The study shows that by using MR-guided biopsy, you find tumors that would have otherwise been undetected in 41% of patients.

Here in the United States, every year, hundreds of thousands of men have negative TRUS-guided biopsies in the search for prostate cancer. In our opinion it would be less than wise to start arguing that every single one of those men ought to have an MRI-guided, targeted biopsy. Many of them would be found to have prostate cancer that is either clinically indolent or potentially clinically insignificant. For men who have a negative TRUS-guided biopsy and a PSA that continues to rise, the argument may well be different, but we think Dr. Barentz’s enthusiasm for his new technique may have led to something of an overstatement … or maybe his quotation was taken out of context.

5 Responses

  1. Is he describing the MR process for his recurrent patients, and not the newly identified?

  2. It would seem to me, with understanding of the value of wide-beam radiation in addressing lymph nodes in salvage EBRT cases, if a patient is Gleason 7 or above, that not using the regional approach that EBRT offers is relying on the hope that only the prostate bed is the source of biochemical failure. It would only make sense to use EBRT. We do know that HIFU, cryotherapy, and seeds will not address any lymph nodes don’t we (at least not significantly)?

  3. John:

    He appears to be describing its use in both categories of patients, but he is only giving data for men with recurrent disease.

  4. Regarding Dr. Barentz comments …

    The following are important methods of ensuring that the anterior as well as the top of the prostate gland are appropriately biopsied, particularly when a biopsy fails to identify prostate cancer despite DRE findings or elevated PSA.

    Hidden tumors located on the top and anterior of the prostate can evade traditional diagnostic procedures, including ultrasound guided needle biopsy. The following two PubMed abstracts address the risk for hidden tumors within the anterior of the prostate:

    A separate article entitled “Hidden prostate cancer tumours evade treatment,” appeared in October 2009.

    Other MRI-based procedures known as VividLook and DynaTRIM also provide methods of sophisticated tumor location.

    From the foregoing, close attention to testing and monitoring diagnostics is of absolute importance by both the physician as well as by the patient. The importance to the patient is in ensuring that his physician is paying close attention by scheduling necessary testing and monitoring. And for those men whose PSA is elevating despite usual biopsy procedures failing to identify the presence of tumor development, it would be prudent to seek out a physician and facility that provides one of the procedures identified in the previous few paragraphs.

  5. Dear Chuck:

    No one is suggesting that there aren’t relatively unusual patients who require special attention in order to ensure that clinically significant prostate cancer is appropriately diagnosed.

    However, I would respectfully suggest that the idea that every patient undergo an MRI-guided form of biopsy (as apparently proposed by Dr. Barentz) if they have a negative initial TRUS-guided biopsy is a guarantee of more over-treatment in the future. This may or may not be what Dr. Barentz intended to say, but it is what he is quoted as saying.

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