Improving care for prostate cancer patients was a dominant theme at this year's ASTRO Annual Meeting, and was also specifically the subject of the Presidential Symposium (“Prostate Cancer: Patient-Focused Advances”). There were significant developments with regard to the establishment of clinical practice guidelines, the choice of appropriate treatment modalities, and the refinement of treatment recommendations for men with prostate cancer.
Two studies were presented that help to refine treatment recommendations for men with intermediate-risk prostate cancer. The first (Abstract 1, Pisansky) presented the 10-year results of RTOG 9910. This was a phase III trial comparing eight weeks of neoadjuvant total androgen blockade (TAB) vs. 28 weeks of concurrent TAB with radiation therapy to 70 Gy for men with intermediate-risk prostate cancer.
At a median follow-up of 10 years, there was no significant difference in the endpoints of biochemical relapse-free survival, disease-specific survival, distant metastasis-free survival, local failure, or overall survival—all of which, with the exception of biochemical relapse-free survival, were excellent.
The authors emphasized the importance of the currently active RTOG 0815 trial, which will help to clarify the role of TAB with dose escalation for this cohort of men, as well as the need for improvements in biochemical and toxicity endpoints.
The results of a secondary analysis of intermediate-risk prostate cancer patients on RTOG 9202 were also presented, querying the necessity of two years of adjuvant androgen deprivation in this cohort (Abstract 61, Mirhadi). To this end, the 10-year outcomes for the 71 intermediate-risk patients who received four months of androgen deprivation were compared with those of the 59 patients in the long- course arm. The results showed no difference with regard to prostate-specific antigen (PSA) failure, survival, or disease recurrence between the two arms, leading the authors to the conclusion that intermediate-risk patients did not require long-course androgen-deprivation therapy.
Reflecting the emerging theme of improving and standardizing treatment recommendations across allied specialties, the ASTRO/AUA consensus guidelines for the recommendation of radiation therapy for post-prostatectomy patients were presented. These guidelines were achieved through evidence-based and consensus review of 324 research articles in English-language publications from 1990 to 2012, and focused on a detailed analysis of efficacy, toxicity, and quality-of-life endpoints for patients with detectable and undetectable PSA levels after prostatectomy.
The consensus group arrived at nine recommendations:
1. Patients being considered for management of localized prostate cancer with radical prostatectomy should be informed of the potential for adverse pathologic findings that portend a higher risk of cancer recurrence;
2. Patients with adverse pathologic findings, including seminal vesicle invasion, positive margins, and extraprostatic extension should be informed that adjuvant radiation therapy, compared with radical prostatectomy only, reduces the risk of biochemical PSA recurrence;
3. Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at the time of prostatectomy, because of demonstrated reductions in biochemical recurrence, local recurrence, and clinical progression;
4. Patients should be informed that the development of a PSA recurrence after surgery is associated with a higher risk of development of metastatic prostate cancer or death from the disease;
5. Clinicians should define biochemical recurrence as a detectable or rising PSA value after surgery that is ≥0.2 ng/ml with a second confirmatory level ≥0.2 ng/ml;
6. A restaging evaluation in the patient with a PSA recurrence may be considered;
7. Physicians should offer salvage radiation therapy to patients with PSA or local recurrence after radical prostatectomy in whom there is no evidence of distant metastatic disease;
8. Patients should be informed that the effectiveness of radiation therapy for PSA recurrence is greatest when given for lower levels of PSA; and
9. Patients should be informed of the possible short-term and long-term urinary, bowel, and sexual side effects of radiation therapy, as well as the potential benefits of controlling disease recurrence.
Two Prostate Cancer Recommendations in ‘Choosing Wisely’ List
ASTRO also released its list for the ABIM Foundation's “Choosing Wisely” campaign, and included in those five recommendations were two related to prostate cancer treatment: (1) “Don't initiate management of low-risk prostate cancer without discussing active surveillance;” and (2) “Don't routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry”— given the cost of proton therapy and in light of the lack of clear evidence that proton beam therapy for prostate cancer offers any clinical advantage over other forms of definitive radiation therapy.
Finally, an interesting study was presented to further stratify and characterize intermediate-risk patients using genetic analyses. The study demonstrated a negative association between genomic instability in common fragile sites and treatment outcome for men with intermediate-risk prostate cancer.
In the study, the presence of genomic instability was a significant independent prognostic factor of outcome in patients treated with radiotherapy. Men matched based on PSA, Gleason score, and stage with tumors that did not demonstrate genomic instability had a 90 percent biochemical relapse-free survival versus 64 percent in those who did.
Although the results need to be validated with additional studies, the test, and others like it, could help identify those men at higher risk for failure and allow for tailored intensification of their treatment.