Active surveillance – a great alternative to curative therapies
The ‘active surveillance’ protocol has become an alternative to curative therapy for prostate cancer that is unlikely to be biologically or clinically significant. However, Dr Riccardo Valdagni, Director, Radiation Oncology, European School of Oncology says men who choose to be monitored under ‘active surveillance’ need to be thoroughly informed of their disease and the observational program
Prostate cancer is the most common malignancy among men, with estimated 1.446.483 new case and 715.257 deaths in 2012. The number of diagnoses has increased since the introduction of PSA as a routine exam in the early Nineties. The good thing is that up to 50% of the new prostate cancers detected can be considered clinically insignificant or indolent. This is a relatively new concept in oncology and means that these very well localised, small and non aggressive tumors, which are diagnosed with a biopsy following PSA rises, would not cause symptoms and/or cause death during one’s life.
Despite this non aggressive behaviour, most of these tumors are still treated with curative standard therapies, i.e. prostatectomy, external radiotherapy and brachytherapy, equally effective treatment options, burdened though by potentially severe side effects. At the same time, we should consider the other side of the coin: there is no way to entirely distinguish upfront, before as well as after the biopsy, non aggressive, clinically insignificant, indolent tumors from aggressive, potentially lethal cancers that need to be treated immediately.
In this context of overdiagnosis (cases of early prostate cancer diagnosed following a suspicious PSA, in absence of symptoms) and over treatment (cases of prostate cancer treated despite their non aggressive and potentially non lethal behaviour) active surveillance should be routinely proposed in alternative to radical treatment to very selected men with favourable disease characteristics (in general, PSA < 10 ng/mL, limited disease burden, Gleason score 3+3).
Active surveillance is an observational program which monitors the disease by PSA (usually every 3 months), digital rectal examination (usually every 3-6 months) and follow up biopsy (the frequency of the procedures differs according to protocols, with the first rebiopsy usually after 12 months since diagnosis). An extra biopsy could be prescribed if the PSA Doubling Time, which evaluates the PSA trend over time, is less than 10 years and causes worries. Another exam that has recently gained a new emerging role is the multiparametric Magnetic Resonance Imaging, a very sophisticated procedure which is able to identify areas of more aggressive disease and thus be helpful in addressing and targeting biopsy.
Considering the slow evolution of low and very low risk prostate tumors and the possibility of maintaining the chances of curability if treatment becomes necessary, active surveillance permits to avoid or delay treatment and therapy induced side effects until the eventual change of the tumor initial characteristics. It is therefore clear that follow up plays a crucial role since it enables us to monitor the tumor behaviour and potentially detect the more aggressive forms, which may benefit from treatment. It is for this reason that active surveillance protocols need to have well defined criteria for inclusion, follow up and discontinuation. This helps in the selection and monitoring of patients, ready to switch to treatment if the tumor behavior changes.
Reasons to discontinue the active surveillance program are usually related to the reclassification of the disease at the rebiopsy. Data coming from the pathologic results shows the upsizing, that is the increase in the number of positive cores over the limit stated in the protocol, and the upgrading, which is the change of the Gleason score, i.e higher than 3+3. Reclassification at biopsy more often happens in the first two years of active surveillance. If this is the case, it most likely does not mean the initially diagnosed tumor is evolved in a more aggressive form, rather the second biopsy enabled to better sample the prostate. Until a few years ago another cause to discontinue active surveillance was PSA Doubling Time if less than 3 years. Since active surveillance studies showed that PSA Doubling Time is not reliable enough to predict an aggressive tumor, it is now considered a warning to be paid attention to, which might induce the prescription of an extra biopsy or a multiparametric Magnetic Resonance Imaging when available, rather than the immediate discontinuation of the active surveillance program.
Although active surveillance is included as an option for low and very low risk prostate cancer in the most important international guidelines, further research is urgently needed to better understand the nature of the tumor and trying to take benefit from non-invasive indicators of its progression or reclassification. Research is currently focused on finding genetic signatures of positive biopsy and adjacent normal tissue and on studying biomolecular markers possibly present in urine and blood (the so called liquid biopsy). Until then, even if AS is part of the most important international guidelines, we believe that active surveillance should be proposed within protocols authorized by the institutional Ethical Committee.
What is more, men with prostate cancer who choose to be monitored in active surveillance protocols need to be thoroughly informed of their disease and the observational program. It is important that these patients understand that active surveillance is proposed as an alternative to curative therapies and should be considered in the same way as a treatment.
Men need to accept and be compliant to the follow up program, which includes periodic biopsies, a procedure with potential side effects they have to be made aware of. After being well informed on active surveillance, men with prostate cancer should sign an informed consent and thus share with their clinicians the responsibility of being on surveillance.