A. Mahadevan

Quality of Life and Satisfaction with Outcome among Prostate-Cancer Survivors

BACKGROUND We sought to identify determinants of health-related quality of life after primary treatment of prostate cancer and to measure the effects of such determinants on satisfaction with the outcome of treatment in patients and their spouses or partners. METHODS We prospectively measured outcomes reported by 1201 patients and 625 spouses or partners at multiple centers before and after radical prostatectomy, brachytherapy, or external-beam radiotherapy. We evaluated factors that were associated with changes in quality of life within study groups and determined the effects on satisfaction with the treatment outcome. RESULTS Adjuvant hormone therapy was associated with worse outcomes across multiple quality-of-life domains among patients receiving brachytherapy or radiotherapy. Patients in the brachytherapy group reported having long-lasting urinary irritation, bowel and sexual symptoms, and transient problems with vitality or hormonal function. Adverse effects of prostatectomy on sexual function were mitigated by nerve-sparing procedures. After prostatectomy, urinary incontinence was observed, but urinary irritation and obstruction improved, particularly in patients with large prostates. No treatment-related deaths occurred; serious adverse events were rare. Treatment-related symptoms were exacerbated by obesity, a large prostate size, a high prostate-specific antigen score, and older age. Black patients reported lower satisfaction with the degree of overall treatment outcomes. Changes in quality of life were significantly associated with the degree of outcome satisfaction among patients and their spouses or partners. CONCLUSIONS Each prostate-cancer treatment was associated with a distinct pattern of change in quality-of-life domains related to urinary, sexual, bowel, and hormonal function. These changes influenced satisfaction with treatment outcomes among patients and their spouses or partners.

Prediction of Intrafraction Prostate Motion: Accuracy of Pre- and Post-Treatment Imaging and Intermittent Imaging

PURPOSE To evaluate whether pre- and post-treatment imaging (immediately before and after a radiation therapy treatment fraction) and intermittent imaging (at intervals during a treatment fraction) are accurate predictors of prostate motion during the delivery of radiation. METHODS AND MATERIALS The Calypso 4D Localization System was used to continuously track the prostate during radiation delivery in 35 prostate cancer patients, for a total of 1,157 fractions (28-45 per patient). Predictions of prostate motion away from isocenter were modeled for a pre- and post-treatment imaging schedule and for multiple intermittent intrafraction imaging schedules and compared with the actual continuous tracking data. The endpoint was drift of the prostate beyond a certain radial displacement for a duration of more than 30 s, 1 min, and 2 min. Results were used to evaluate the sensitivity and specificity of these models as an evaluation of intrafraction prostate motion. RESULTS The sensitivity of pre- and post-treatment imaging in determining 30 s of intrafraction prostate motion greater than 3, 5, or 7 mm for all fractions was low, with values of 53%, 49%, and 39%, respectively. The specificity of pre- and post-treatment imaging was high for all displacements. The sensitivity of intermittent imaging improved with increasing sampling rate. CONCLUSIONS These results suggest that pre- and post-treatment imaging is not a sensitive method of assessing intrafraction prostate motion, and that intermittent imaging is sufficiently sensitive only at a high sampling rate. These findings support the value of continuous, real-time tracking in prostate cancer radiation therapy.

Outcomes for intermediate risk prostate cancer: Are there advantages for surgery, external radiation, or brachytherapy?

The treatment of localized prostate cancer remains controversial because of the lack of conclusive well-controlled or randomized studies comparing outcome of various forms of radiotherapy (RT) to radical prostatectomy (RP). We review recent results from an institutional database and prospective quality of life study comparing cancer-related and quality of live (QOL) outcomes among different treatment modalities for intermediate risk prostate cancer. The results suggest similar short-term survival but domain-specific effects on QOL after treatment with radical prostatectomy, brachytherapy, or external beam radiotherapy.

Comparison of Biochemical Relapse-Free Survival Between Primary Gleason Score 3 and Primary Gleason Score 4 for Biopsy Gleason Score 7 Prostate Cancer

PURPOSE To determine whether the primary grade (PG) of biopsy Gleason score (GS) 7 prostate cancer (CaP) was predictive for biochemical relapse-free survival (bRFS). Most of the present data regarding the PG of GS7 CaP refer to surgical specimens. Our goal was to determine whether the biopsy GS used at the time of medical decision making predicted for the biochemical outcome. METHODS AND MATERIALS We reviewed the data from 705 patients with biopsy GS7 CaP, from a prospectively maintained database, who had been treated at our institution between September 1996 and March 2005 with radical prostatectomy (n = 310), external beam radiotherapy (n = 268), or prostate radioactive seed implantation (n = 127). The bRFS rates were estimated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used for univariate and multivariate analyses examining these factors in relation to bRFS: PG of biopsy GS, initial prostate-specific antigen level, clinical T stage, use of androgen deprivation, risk group (high or intermediate), and treatment modality. RESULTS The 5-year bRFS rate was 78% and 71% (p = 0.0108) for biopsy GS7 PG3 CaP and biopsy GS7 PG4 CaP, respectively. Comparing PG3 and PG4 within treatment modalities, only prostate implantation patients had a significant difference in the 5-year bRFS rate, 88% vs. 76%, respectively (p = 0.0231). On multivariate analysis, the PG of biopsy GS remained an independent predictor of bRFS, with PG3 having better bRFS than PG4 (relative risk, 0.655; 95% confidence interval, 0.472-0.909; p = 0.0113). CONCLUSION Biopsy GS7 PG4 CaP carries a worse bRFS than biopsy GS7 PG3 CaP.

Renal radiosurgery: initial clinical experience with histological evaluation.

The purpose of this study was to determine whether radiosurgical technology can be safely applied to renal tumors. Patients received radiosurgical treatment of renal lesions. At 8 weeks after radiosurgical treatment, patients underwent a partial or radical nephrectomy and histologic evaluation. The patients received a radiation dose of 4 Gy per fraction for 4 fractions. Patients were followed, and radiation-induced toxicities were noted. Three patients were treated for a minimum of 1 year of follow-up. All patients completed the treatments, tolerating each of the 4 fractions with no adverse events. No acute toxicities or changes in renal function were noted. None of the patients had any evidence of acute radiation injury or toxicity noted at the time of surgery or within the subsequent 12 months after the radiosurgical treatment. The last patient treated was found to have a cavity with no microscopic evidence of viable tumor after radiosurgical treatment; pathology was consistent with necrotic renal cell carcinoma, papillary type. The other 2 tumors demonstrated pathologic evidence of viable renal cell carcinoma (grade I and grade II). Tumor size remained relatively unchanged for 8 weeks after the radiosurgical treatment in all patients. The authors are extremely encouraged and cautiously optimistic with the initial results. Radiosurgery for renal tumors appears to be safe at this initial dose level.

Aggressiveness of Familial Prostate Cancer

PURPOSE To report on the aggressiveness of sporadic versus familial prostate cancer. PATIENTS AND METHODS The study sample consisted of 4,112 stage T1-3 prostate cancer patients. The outcome of interest was biochemical relapse-free survival (bRFS). The analysis was performed for two distinct time periods, 1986 to 1992 (year < or = 1992) and 1993 to 2002 (year > or = 1993), to encompass both the early and late prostate-specific antigen (PSA) eras. RESULTS A positive family history (FH positive) was reported in 16%. The 10-year bRFS rates for patients with negative family history (FH negative) versus FH positive were 59% and 63%, respectively (P = .90). However, in the year < or = 1992 period, the 10-year bRFS rates for FH negative versus FH positive were 45% and 34%, respectively (P = .015). In the year > or = 1993 period, the 10-year bRFS rates for FH negative versus FH positive were 61% and 67%, respectively (P = .54). Multivariate analysis failed to reveal family history as an independent predictor of relapse (P = .42). However, in the subset of patients in each era, family history was an independent predictor of relapse only for those treated in the year < or = 1992 period (P = .038). CONCLUSION Family history was an independent predictor of biochemical failure only early in the PSA era, and men with an FH positive presented with more favorable disease later in the PSA era. This suggests that with stage migration and improved therapy, the impact of family history on prognosis has become minimal. However, underlying genetic factors affecting prostate cancer behavior in individuals with familial prostate cancer may still be important in determining individual prognosis.

Early intervention with phosphodiesterase-5 inhibitors after prostate brachytherapy improves subsequent erectile function.

Study Type – Therapy (case series)
Level of Evidence 4

Realtime Organ Tracking for Endoscopic Augmented Reality Visualization Using Miniature Wireless Magnetic Tracker

Organ motion is one of the problems on augmented reality (AR) visualization for endoscopic surgical navigation system. However, the conventional optical and magnetic trackers are not suitable for tracking of internal organ motion. Recently, a wireless magnetic tracker, which is called the Calypso 4-D localization system has been developed. Since the sensor of the Calypso system is miniature and implantable, position of the internal organ can be measured directly. This paper describes AR system using the Calypso system and preliminary experiments to evaluate the AR system. We evaluated distortion error caused by the surgical instruments and misalignment error of superimposition. Results of the experiments shows potential feasibility and usefulness of AR visualization of moving organ using the Calypso system.

Causes of Mortality After Dose-Escalated Radiation Therapy and Androgen Deprivation for High-Risk Prostate Cancer

PURPOSE Men with high-risk prostate cancer have other competing causes of mortality; however, current risk stratification schema do not account for comorbidities. We aim to identify the causes of death and factors predictive for mortality in this population. METHODS AND MATERIALS A total of 660 patients with high-risk prostate cancer were treated with definitive high-dose external beam radiation therapy (≥ 74 Gy) and androgen deprivation (AD) between 1996 and 2009 at a single institution. Cox proportional hazards regression analysis was conducted to determine factors predictive of survival. RESULTS The median radiation dose was 78 Gy, median duration of AD was 6 months, and median follow-up was 74 months. The 10-year overall survival (OS) was 60.6%. Prostate cancer was the leading single cause of death, with 10-year mortality of 14.1% (95% CI 10.7-17.6), compared with other cancers (8.4%, 95% CI 5.7-11.1), cardiovascular disease (7.3%, 95% CI 4.7-9.9), and all other causes (10.4%, 95% CI 7.2-13.6). On multivariate analysis, older age (HR 1.55, P=.002) and Charlson comorbidity index score (CS) ≥ 1 (HR 2.20, P<.0001) were significant factors predictive of OS, whereas Gleason score, T stage, prostate-specific antigen, duration of AD, radiation dose, smoking history, and body mass index were not. Men younger than 70 years of age with CS = 0 were more likely to die of prostate cancer than any other cause, whereas older men or those with CS ≥ 1 more commonly suffered non-prostate cancer death. The cumulative incidences of prostate cancer-specific mortality were similar regardless of age or comorbidities (P=.60). CONCLUSIONS Men with high-risk prostate cancer are more likely to die of causes other than prostate cancer, except for the subgroup of men younger than 70 years of age without comorbidities. Only older age and presence of comorbidities significantly predicted for OS, whereas prostate cancer- and treatment-related factors did not.

Role of Radiation Therapy in Advanced Renal Cell Carcinoma

Renal cell cancer is an increasingly common tumor involving mostly adults. Surgical excision is the treatment of choice and recently surgical innovation has resulted in excellent outcomes for nephron sparing surgery. Energy based ablative procedures are being increasingly explored as an alternative to surgery to minimize morbidity. Radiation therapy has had relatively little role in the management of patients with renal cell cancer. Advances in the imaging, treatment planning and treatment delivery has made radiation treatments safer now than ever before. In advanced renal cell cancer, radiation therapy can play a role in the management of extensive disease in patient’s with poor overall condition, adjuvant to surgical or other ablative procedures and in patients with metastatic disease.