Since the introduction of PSA as a screening tool for prostate cancer, most cases (about 80%) of prostate cancer are diagnosed when it is still confined to the gland. However, about 15% of patients are diagnosed with metastatic disease in the lymph nodes around the prostate (i.e. locoregional metastases, or stage cN1.) One study found that the stage at diagnosis is important, since there is a 90-99% 5-year survival for organ-confined disease but only a 60-80% 5-year survival for patients with locoregional metastases.
What the Research Says About Treating Prostate Cancer After it’s already Spread
While it is fairly clear that clinically-significant organ-confined disease should be treated with a targeted therapy (radical prostatectomy, radiation therapy, or focal therapy), there has been debate about the utility of targeted therapy in cases where the cancer has already escaped into the adjacent lymph nodes. Some physicians manage these patients with systemic therapy alone (usually androgen deprivation therapy or “ADT”) while others will combine it with a targeted therapy.
A recently published meta-analysis in the journal European Urology Oncology sought to compare the outcomes of the two treatment strategies. Researchers included 8 retrospective studies with a total of 8522 patients with stage cN1 prostate cancer. 5717 patients received local therapy; 1723 patients underwent radical prostatectomy + ADT and 3994 received radiation therapy + ADT. 2805 patients were treated with ADT alone or observed. Patients who received local therapy had significantly longer overall survival (OS) than those who did not receive it for all timepoints from 2 to 10 years. There was no statistically-significant difference in overall survival of radiotherapy versus radical prostatectomy at 2 or 4 years.
At first glance, these results might seem counterintuitive. When patients die of prostate cancer, it is often because of complications from distant metastases, paraneoplastic phenomena, or metabolic derangements caused by androgen deprivation therapy, rather than growth of the tumor in the prostate itself. Treating the cancer within the prostate itself might lower the risk of malignant urinary obstruction and subsequent renal failure, which occurs in about 10% of patients with metastatic disease, but it wouldn’t do anything to the cells which have already escaped.
The most likely explanation for the benefit in overall survival is the marked reduction in the overall number of cancer cells within the body. Each cancer cell can divide into two cells, and each of those cells can divide into two cells and so on. By decreasing the overall number of cells, you may not be “curing” the patient, but you are mathematically resetting the clock. In addition, each cell division allows for the tumor to acquire somatic genetic mutations which could make it more aggressive. By reducing the number of cells which can undergo division, you are decreasing the potential for mutagenesis.
Prostate Laser Center’s Opinion on Study’s Findings
The reduction in PSA caused by treatment may also play a role in increasing survival. While we think about PSA as a biomarker that can indicate the presence of prostate cancer, its role in the body is as an enzyme. When produced by the glandular tissue of the prostate, it is secreted into the semen and helps to keep it in a liquid state. However, in the presence of prostate cancer, it has been demonstrated in both in vitro and in vivo studies that PSA signals the growth of cancer cells. By reducing the PSA produced by both cancerous and noncancerous cells, local treatments including focal laser ablation may decrease the growth signaling, and slow progression of disease in the remaining cancer cells.
The findings of this meta-analysis are very promising. In our practice, we rarely consider patients with locoregional disease ineligible for focal laser ablation or TULSA-PRO. However, this study raises an important question: if targeted whole-gland therapies + ADT confer a survival benefit in these patients, could a near-total treatment with a focal therapy (which has fewer side effects than prostatectomy or radiation) + ADT achieve similar results? We are not suggesting such a management strategy outside of a clinical trial; however, a survival benefit seems at least mechanistically plausible and an exciting topic for future research.
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NOTE: The information provided on this website is general medical information and does not establish a physician-patient relationship. Please discuss your particular situation with a qualified medical professional.