Men with advanced prostate cancer treated with radical prostatectomy and adjuvant radiotherapy have a lower risk of cancer-specific death and improved overall survival compared to men treated with radiotherapy plus androgen deprivation therapy, according to our recent observational study.
The ten-year prostate cancer–specific survival rate for men undergoing radical prostatectomy plus radiotherapy was 89 percent compared to 74 percent in the group undergoing radiotherapy plus androgen deprivation therapy. Overall ten-year survival rates were 64 and 48 percent, respectively. (1)
Surgical treatment for high-risk prostate cancer is not conventionally used: The procedure can be technically challenging and may carry an increased risk of positive margins, biochemical recurrence of prostate specific antigen (PSA), or distant relapse. As a result, trends have shifted away from radical prostatectomy toward higher use of radiotherapy and androgen deprivation therapy. But little comparative data from randomized trials exist to compare outcomes for these two substantially different approaches. (1)
Our findings add substantial evidence for a surgical approach in the debate about the optimal treatment options for men with high-risk prostate cancer. Moreover, the findings show that this subset of patients can achieve durable long-term cancer-specific survival and overall survival with multimodal treatment, as opposed to monotherapy.
High-Risk Prostate Cancer
At least 10 percent of men will have locally or regionally advanced prostate cancer at the time of diagnosis that puts them at a high risk of death from their disease.(2),(3), (4)
The clinical practice guidelines on prostate cancer — from the National Comprehensive Cancer Network (NCCN) (5) and the European Association of Urology–European Society for Radiotherapy and Oncology–International Society of Geriatric Oncology (6) — support multimodal treatment (including radical prostatectomy followed by radiotherapy, and radiotherapy plus androgen deprivation therapy) as appropriate approaches.
Study Results
We examined Surveillance, Epidemiology, and End Results (SEER) Program Medicare data from 1992 to 2009 for 13,856 men 65 years and older with locally advanced (T3-T4N0M0) or regionally advanced (T3-T4N1M0) prostate cancer. The data were sourced from 17 cancer registries, representing 28 percent of the American population. (1)
We observed several key findings. First, the evidence indicated nonadherence to the NCCN and EURO guidelines, which recommend multimodal treatment for men with high-risk prostate cancer for half of the cases studied. We found that 50 percent of men (n=6,970) received a single intervention, and 20 percent (n=2,766) did not receive any treatment within six months of diagnosis. For men who did receive treatment, radiotherapy plus androgen deprivation therapy was most commonly delivered (n=3,272, 24 percent), followed by radical prostatectomy plus radiotherapy (n=848, 6 percent). Not surprisingly, patient age, comorbidities, and cancer stage were associated with treatment received: Younger men with fewer comorbidities and cancers with extracapsular extension (T3aN0M0) or seminal vesicle invasion (T3bN0M0) without regional lymph node involvement were more likely to receive radical prostatectomy plus radiotherapy rather than radiotherapy plus androgen deprivation therapy. (1)
Second, men who received primary radical prostatectomy followed by radiotherapy were significantly less likely to die from their disease and had improved overall survival than men who received radiotherapy plus androgen deprivation therapy. Notably, these findings were independent of primary tumor stage, nodal stage, or Gleason score, although survival was best among men without lymph node metastases. The adjusted ten-year prostate cancer–specific survival rates for men with T3a/bN0M0 disease, T3a/bN1M0 disease, and T4N0M0 disease were 89, 76, and 72 percent, respectively, for those who received radical prostatectomy plus radiotherapy, and 74, 59, and 60 percent, respectively, for those who received radiotherapy plus androgen deprivation therapy. These observations were all within a 95 percent confidence interval. (1)
Note that we reported our findings excluding PSA data, as the quality of PSA data captured in SEER has come into question recently. (7) We performed sensitivity analyses and found that including or excluding PSA data did not significantly alter our findings. (1)
Third, men who received radical prostatectomy plus radiotherapy versus radiotherapy plus androgen deprivation therapy had higher rates of urinary incontinence (49 versus 19 percent, p<0.001), erectile dysfunction (28 versus 20 percent, p=0.0212), and bladder neck contractures and urethral strictures (38 versus 18 percent, p<0.001), respectively. We did not observe any significant differences between groups in rates of hematuria, radiation cystitis, rectal bleeding, radiation proctitis, urinary or gastrointestinal fistulas, acute myocardial infarction, sudden cardiac death, osteoporosis, or fractures. (1)
Observational Study Limitations
Since this analysis was observational and patients were not randomized to treatment approaches, the findings are directional. SEER data is designed for billing purposes, so crucial information that may influence the results, such as radiation dosage or whether patients received nerve-sparing surgery, is not precisely captured. Using Medicare claims to measure adverse events is a crude estimate, since codes may not be specific enough to capture diagnoses or procedures related to complications. (1)
Finally, it is important to note that since 2009, the last year for data capture in this observational study, there have been many advances in prostate cancer surgery and radiotherapy approaches that have served to improve outcomes further while reducing adverse events, such as erectile dysfunction and urinary incontinence.
Advancing Prostate Cancer Care
At Memorial Sloan Kettering, we tailor multimodal approaches to the individual features of each patient’s cancer. Radical prostatectomy is a complex procedure that requires a high level of technical precision. We provide state-of-the-art surgical techniques, including minimally invasive robotic and nerve-sparing surgery. Over the past few decades, we have dramatically reduced surgical complications by incorporating imaging test results in surgical plans to ensure the avoidance of other structures and the minimization of the risk of incontinence and erectile dysfunction. Our multidisciplinary prostate cancer team includes radiation oncologists who provide the latest radiotherapy approaches, including image-guided and intensity-modulated radiation therapy, stereotactic radiosurgery, proton therapy, and brachytherapy.
The field of prostate cancer care is evolving rapidly. We continue to explore new ways to improve outcomes and safety and effectiveness through clinical trials, in which we are testing new drugs and drug combinations, surgery and radiation therapy techniques, diagnostic approaches, and strategies for improving quality of life for men undergoing treatment for prostate cancer.
Acknowledgment: This research was conducted in collaboration with colleagues at Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Weill Cornell Medicine, the Sidney Kimmel Cancer Center, Thomas Jefferson University, Sidney Kimmel Medical College, and Jefferson College of Population Health. It was supported by the New Jersey Health Foundation and the National Cancer Institute.
Disclosure: Peter Scardino sits on a clinical advisory board for OPKO Health outside the submitted study; he also holds a patent issued by OPKO.
