Do you have any Alternatives to
Radical Surgery or Radiation Therapy
for Prostate Cancer?
Yes you do!
ACTIVE SURVEILLANCE and
FOCAL ABLATION...read on!
1. Active Surveillance
Active surveillance for prostate cancer: Overview and update - Abstract
Published on 12 February 2013
Overtreatment of many conditions diagnosed by screening has become increasingly recognized as a contemporary malady associated with modern medicine's efforts at earlier detection.
The diagnosis of low-grade prostate cancer clearly qualifies as an example of potential overdiagnosis and overtreatment. Active surveillance for low-risk prostate cancer is an attempt to reduce the overtreatment of the disease. The approach involves initial expectant management rather than immediate therapy. Curative treatment is deferred while the patient is monitored and offered for evidence of risk reclassification to a more aggressive form of the disease. The basis for this approach is substantial evidence confirming the long natural history of most prostate cancers. The objective is to balance the risks of overtreatment and associated adverse quality of life effects, against the risk of progression of disease and a missed opportunity for curative therapy. Low-risk prostate cancer is more accurately viewed as one of several risk factors for the patient harboring higher-grade disease, rather than a life-threatening condition. This approach is similar to that taken historically for so-called precancerous conditions, such as PIN or ASAP, where patients were managed with close follow-up but without radical intervention unless clear evidence of more aggressive disease is identified. Active surveillance is increasingly viewed as the management of choice for patients with very low-risk (low-grade, low-volume prostate cancer) and low-risk (low-grade but higher volume) disease.
Klotz L. Are you the author?
Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave MG 408, Toronto, M4N 3M5, Ontario, Canada.Laurence.firstname.lastname@example.org
Reference: Curr Treat Options Oncol. 2013 Jan 15. Epub ahead of print.
The economics of active surveillance for prostate cancer - Abstract
Published on 03 April 2013
PURPOSE OF REVIEW: To review the economics of managing low-risk prostate cancer with active surveillance compared with other standard therapies.
RECENT FINDINGS: The expenses of caring for men with prostate cancer vary depending on treatment modality chosen and appear to be escalating. Costs are generally lowest with traditional watchful waiting and highest with radiation therapy. Compared with immediate treatment, active surveillance can result in a net per-patient savings of $12?194 at 5 years and $4329 at 10 years. Active surveillance demonstrates lower 5-year costs over other initial treatments as long as fewer than 70% exit active surveillance in any given year and at least 12% of men remain on active surveillance at year 5. Yearly surveillance biopsy reduces the average simulated cost savings at 10 years by $4951 per patient.
SUMMARY: Active surveillance represents a cost-effective strategy for managing low-risk prostate cancer, as the majority of men remain without additional treatment over time. Prostate biopsy is the highest expenditure associated with active surveillance, and increasing the frequency of prostate biopsy will reduce the cost-effectiveness of this approach.
Dall'era MA. Are you the author?
Department of Urology, University of California, Sacramento, California, USA.
Reference: Curr Opin Urol. 2013 Feb 27. Epub ahead of print.
Prostate cancer mortality following active surveillance versus immediate radical prostatectomy - Abstract
Published on 18 October 2013
PROPOSE: Active surveillance has been endorsed for low-risk prostate cancer, but information about long-term outcomes and comparative effectiveness of active surveillance is lacking.
The purpose of this study is to project prostate cancer mortality under active surveillance followed by radical prostatectomy versus under immediate radical prostatectomy.
EXPERIMENTAL DESIGN: A simulation model was developed to combine information on time from diagnosis to treatment under active surveillance and associated disease progression from a Johns Hopkins active surveillance cohort (n = 769), time from radical prostatectomy to recurrence from cases in the CaPSURE database with T-stage ≤ T2a (n = 3,470), and time from recurrence to prostate cancer death from a T-stage ≤ T2a Johns Hopkins cohort of patients whose disease recurred after radical prostatectomy (n = 963). Results were projected for a hypothetical cohort aged 40 to 90 years with low-risk prostate cancer (T-stage ≤ T2a, Gleason score ≤ 6, and prostate-specific antigen level ≤ 10 ng/mL).
RESULTS: The model projected that 2.8% of men on active surveillance and 1.6% of men with immediate radical prostatectomy would die of their disease in 20 years. Corresponding lifetime estimates were 3.4% for active surveillance and 2.0% for immediate radical prostatectomy. The average projected increase in life expectancy associated with immediate radical prostatectomy was 1.8 months. On average, the model projected that men on active surveillance would remain free of treatment for an additional 6.4 years relative to men treated immediately.
CONCLUSIONS: Active surveillance is likely to produce a very modest decline in prostate cancer-specific survival among men diagnosed with low-risk prostate cancer but could lead to significant benefits in terms of quality of life.
2. Focal Cryotherapy
Cryotherapy is the freezing of tumor cells leading to their destruction. This can be applied in a very precise fashion using ultrasonically guided probes into the prostate gland.
Massimo Valerio*1–3, Mark Emberton1,
2, Eric Barret4,
Daniel Eberli5, Scott E
Eggener6, Behfar Ehdaie7, Patrice Jichlinski3, John F
Hashim U Ahmed1, 2 1Division of Surgery
and Interventional Science, University College London,
Focal therapy in prostate cancer aims to
treat only the part of the gland harboring
clinically significant disease while preserving the
rest of the tissue.
This approach may substantially reduce treatment
related toxicity without compromising disease control. Short- to medium-term functional and
oncological results in prospective interventional studies
are promising, but comparative effectiveness research against
standard of care is required to incorporate focal therapy among standard options. In
this review, we discuss the actual stage of assessment and results of
sources of energy commonly used to deliver focal therapy.
We also provide our viewpoint on how the field will
evolve in the near future.
Prostate cancer is the most frequent
solid tumor among men. The use of formal and
informal screening practices in many Western countries in the last three
decades has led to an increase in its incidence by around 50% . Since only a
modest decrease in the mortality rate has been observed during this increase,
the use of invasive diagnostics for formal screening and radical treatments is
being questioned by clinicians, scientists, policy makers and ultimately
by patients and governments [2–4].
Recently, a number of randomized con- trolled trials
(RCTs) have better clarified the benefit of screening and treatment in prostate
cancer. First, the prostate, lung, colon and ovaries screening trial in the USA
showed no evidence of an overall survival benefit and was criticized for
significant PSA screening rates (45%) prior to randomization and contamination
(i.e., PSA testing) in the control arm . Nonetheless, it
seemed to show survival benefit limited to men with few comorbidities . Second, the
European Randomized Study of Screening for Prostate Cancer, a European
multicenter study allocating men to either screening or standard practice, has
shown a 21% decreased risk of death from prostate cancer for men
undergoing screening, at least after 11 years follow-up. Third, the
Prostate Cancer Intervention Versus Observation Trial, an American
multicenter study comparing the survival of men with prostate cancer
assigned to radical prostatectomy or to watchful waiting, has shown that
after a median follow-up of 10 years, the benefit in favor of surgery was
restrained to men with intermediate risk dis- ease and possibly to few
other well-selected categories . This
is supported by the Scandi- navian Prostate Cancer Group-4 study, which
recruited men diagnosed clinically without PSA testing and therefore a
high-risk population, which showed survival benefits in treating with
In summary, though there are some conflicting results, the
preponderance of evidence regarding the benefits of screening for prostate
cancer has shown a survival benefit but the advantage is limited to selected
men, primarily with intermediate or high-risk characteristics. The concern
remains, however, that this advantage comes at the risk of overdiagnosis and
overtreatment with concomitant harms to men who may not have clinically
significant disease . The dilemma of
patients and clinicians advising patients is even more profound, given the
significant proportion of men having toxicity after current radical radiation
therapy and radical prostatectomy. Indeed, although there is no definitive
evidence of superiority of one therapy compared with the other and
the photodynamic therapy (PDT), laser
interstitial thermotherapy (LITT) and irreversible electroporation toxicity profile is
different, the incidence of genitourinary and rectal toxicity is high and
roughly comparable in terms of severity for both treatments as
well as downstream further healthcare interventions and use of healthcare
resources . Further,
technological improvements in the delivery of radical prostatectomy,
for instance, seem not to have made a significant impact on long-term
functional outcomes .
To balance the unfavorable risk/benefit ratio of current
standard treatments, new approaches and novel technologies are being explored.
Hitherto, prostate cancer therapy has been traditionally directed towards the
whole gland rather than to the area of the gland harboring cancer. It is one of
the outliers in terms of cancer therapy with most other solid organ cancers
having therapy directed to the tumor and not primarily to the whole organ in
the majority of cases. For the prostate, a consequence of whole-gland treatment
is that surrounding structures are at risk of damage with consequent urinary,
erectile and bowel side effects. However, new evidence has
highlighted that only the index lesion – largest by volume
and/or grade – typically drives the natural history of the disease
despite prostate cancer being multifocal in most men [14–16]. Thus, a
new approach delivering treatment only to the area of the gland affected by
significant disease might be a reasonable approach and the best way to preserve
function while retaining the benefits of cancer control. This approach
has been called ‘focal therapy’ [17,
In this review, we will discuss the current outcomes, the
stage of the evaluation and how the field is likely to develop in the available
sources of energy employed for delivering focal therapy: cryotherapy,
high-intensity focused ultrasound (HIFU),
How do we assess health technology?
Before discussing the results and the future of
focal therapy, it seems useful to analyze how new health technologies should be
properly evaluated in order to provide meaningful results with a feasible
methodology. Health technology assessment refers to the evaluation of
procedures undertaken by health providers measured with respect to
effectiveness, cost or impact . The Medical Research Council has released specific recommenda-tions to
assist researchers committed to health technology assessment . Similarly, the
Balliol collaboration has clarified the progressive steps in which novel
surgical procedures should be properly investigated; briefly, the four
development stages, which in drug assessment are known as phases, are represented
in the acronym IDEAL (Idea, Development, Evaluation and Assessment and
Long-term results) that also gives the name to this framework .
Each letter of the IDEAL acronym represents one
stage with stage II being divided into two substages, IIa (Development) and IIb
(Evaluation). Each of the four stages has a specific purpose, primary outcome,
outcome measure and methodology. Using the IDEAL framework, we have evaluated
the body of evidence available in order to define the stage of health assessment
for each source of energy.
The state of the art Focal cryotherapy
Using extreme cold temperatures, cryoablation provokes
cell death by various mechanisms: permanent damage to the external
cell membrane, cytolysis, ice crystal formation, ischemic necrosis and
apoptosis. Although this source of energy is known to be very effective against
prostate cancer, it was not before significant technological developments were
made that this source of energy became very attractive in prostate cancer.
Mainly, third-generation cryotherapy devices are able to use gas-based systems in
order to provide rapid freeze and thaw cycles. Also, manufacturers have been
able to develop multiprobe systems while decreasing the size of each cryoprobe,
so the precision of ablation could be enhanced. Finally, the toxicity has
significantly decreased because of the use of safety measures such as a
continuous urethral warmer during the treatment, and the systematic employment
of thermocouples for verifying the temperature both in critical surrounding
structures and in the treatment area .
Focal cryotherapy to an area of the prostate is
delivered under transrectal ultrasound (TRUS) guidance using cryoneedles
inserted via the perineum using a brachytherapy grid or by a free-hand
fashion (FIGURE 1).
Further, thermocouples are positioned in the same way, normally in the
treatment area, in the Denonvillier’s fascia, and in other key areas,
Rhabdosphincter and the neurovascular bundles at discretion
of the surgeon. A urethra–cystoscopy is warranted before beginning the
treatment in order to verify the position of the needles; finally, a continuous
urethral warmer to protect the urethra is inserted and maintained during the
whole procedure. In addition to the standardized technique, in 2008, the
American Urological Association has released a best practice statement to
underline the optimal procedural requirements to deliver effective cryotherapy.
The Panel recommended a double freeze–thaw cycle, the use of rapid freezing
up to -40?C with slow, almost passive, thaw .
Most of the outcomes of focal cryotherapy as first-line
treatment is derived from the COLD-registry, which is an online database  supported by
a private manufacturer, and independently managed by a research company
(Watermark, Indianapolis, IN, USA) and a medical advisory board. The registry
has no restricted eligibility for patients who are selected by their surgeon,
following local guidelines with the approval of the Institutional Review Board.
In the latest report from the COLD-registry, 1160 men were
treated with focal cryoablation . In
terms of cancer control, the 3-year biochemical disease-free survival
(BDFS) was at 75.7%, the positive biopsy rate 26.3%, considering
only the patients who underwent biopsy because of biochemical failure, or
at 3.7%, if the whole cohort of patients is considered the denominator. In
terms of functional outcomes, urinary incontinence was found in 1.6%
of men, whereas 41.9% men had new erectile dysfunction, and rectourethral
fistula occurred in only 0.1% of the cases. Despite the efforts of the
researchers and the large sample size, the COLD registry has some
significant flaws, such as the absence of entry criteria, of
on-site quality control and traceability of data, as well as
lack of patient-reported outcome measures (PROMs).
Other small series have reported on
outcomes after focal cryotherapy, but no series so far had a comparative group,
and none had strict design in terms of outcome measures [26–28]. In
one case series, 73 men were treated by hemiablation and underwent systematic
biopsy within the first year. Only one patient had residual disease in the
treated lobe, whereas 11 men had cancer identified on the untreated side.
Interestingly, in a matched-pair analysis with men undergoing radical
prostatectomy, there was no difference in the cancer control outcome, as
defined by the transition to salvage treatment . In
this same series, 100% and 86% were continent and potent, respectively, after
The first prospective stage II trial
of focal therapy using cryoablation has recently been reported. Unlike all prior reports of focal cryoablationwhere
a treatment template incorporated the identified index lesion
along with a margin surrounding normal tissue, in this prospective study,
Zarqawi et al. aimed to eradicate all clinically detected
Sixty-two men with low-risk disease (Gleason £ 3+4
with less than 50% positive core and four or fewer zones involved with cancer
excluding the periurethral zone) were included. Patients underwent 3D template
mapping biopsy in order to qualify for treatment. Targeted focal cryotherapy
was per- formed using variable length cryoneedles positioned in all zones that
showed at least one positive core on 3D mapping biopsy. No cancer was found in
50 of the 62 men (81%) undergoing biopsy after 1 year. Importantly, there was
no significant change in erectile function, as measured by validated
questionnaires, and no urinary incontinence or severe adverse events were
reported following treatment.