Al V. Taira

Performance of transperineal template-guided mapping biopsy in detecting prostate cancer in the initial and repeat biopsy setting

Transrectal ultrasound (TRUS) biopsy can miss 20–30% of clinically significant cancers. We evaluate an alternative approach—transperineal template-guided mapping biopsy (TTMB) in the initial and repeat biopsy setting. From January 2005 through September 2008, 373 consecutive men underwent TTMB (294 men with ⩾1 prior negative biopsy and 79 men as the initial biopsy). The location of each positive biopsy core, number of positive cores, and percent involvement of each core was recorded. Cancer detection rate for the initial biopsy was 75.9%. For men with 1, 2, and ⩾3 prior negative biopsies detection rates were 55.5%, 41.7%, and 34.4%, respectively. In all, 55.5% of the cancers identified were Gleason ⩾7. The majority of the cancers were multifocal. There was no significant change in the number of positive cores or Gleason score as the number of prior biopsies increased. The anterior and apical aspects of the prostate were among the most common cancer locations. TTMB provides a high rate of cancer detection as initial and repeat biopsy. TTMB was particularly effective at diagnosing anterior and apical cancer. TTMB may have particular application for men considering active surveillance, with prior negative TRUS biopsies, and those considering subtotal gland or other minimally invasive treatments.

Long-Term Outcome for Clinically Localized Prostate Cancer Treated With Permanent Interstitial Brachytherapy

PURPOSEnTo present the largest series of prostate cancer brachytherapy patients treated with modern brachytherapy techniques and postimplant day 0 dosimetric evaluation.nnnMETHODS AND MATERIALSnBetween April 1995 and July 2006, 1,656 consecutive patients were treated with permanent interstitial brachytherapy. Risk group stratification was carried out according to the Mt. Sinai guidelines. Median follow-up was 7.0 years. The median day 0 minimum dose covering at least 90% of the target volume was 118.8% of the prescription dose. Cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters.nnnRESULTSnAt 12 years, biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) for the entire cohort was 95.6%, 98.2%, and 72.6%, respectively. For low-, intermediate-, and high-risk patients, bPFS was 98.6%, 96.5%, and 90.5%; CSS was 99.8%, 99.3%, and 95.2%; and OS was 77.5%, 71.1%, and 69.2%, respectively. For biochemically controlled patients, the median posttreatment prostate-specific antigen (PSA) concentration was 0.02 ng/ml. bPFS was most closely related to percent positive biopsy specimens and risk group, while Gleason score was the strongest predictor of CSS. OS was best predicted by patient age, hypertension, diabetes, and tobacco use. At 12 years, biochemical failure and cause-specific mortality were 1.8% and 0.2%, 5.1% and 2.1%, and 10.4% and 7.1% for Gleason scores 5 to 6 and 7 and ≥8, respectively.nnnCONCLUSIONSnExcellent long-term outcomes are achievable with high-quality brachytherapy for low-, intermediate-, and high-risk patients. These results compare favorably to alternative treatment modalities including radical prostatectomy.

Natural History of Clinically Staged Low- and Intermediate-Risk Prostate Cancer Treated With Monotherapeutic Permanent Interstitial Brachytherapy

PURPOSEnTo evaluate the natural history of clinically staged low- and intermediate-risk prostate cancer treated with permanent interstitial seed implants as monotherapy.nnnMETHODS AND MATERIALSnBetween April 1995 and May 2005, 463 patients with clinically localized prostate cancer underwent brachytherapy as the sole definitive treatment. Men who received supplemental external beam radiotherapy or androgen deprivation therapy were excluded. Dosimetric implant quality was determined based on the minimum dose that covered 90% of the target volume and the volume of the prostate gland receiving 100% of the prescribed dose. Multiple parameters were evaluated as predictors of treatment outcomes.nnnRESULTSnThe 12-year biochemical progression-free survival (bPFS), cause-specific survival, and overall survival rates for the entire cohort were 97.1%, 99.7%, and 75.4%, respectively. Only pretreatment prostate-specific antigen level, percent positive biopsy cores, and minimum dose that covered 90% of the target volume were significant predictors of biochemical recurrence. The bPFS, cause-specific survival, and overall survival rates were 97.4%, 99.6%, and 76.2%, respectively, for low-risk patients and 96.4%, 100%, and 74.0%, respectively, for intermediate-risk patients. The bPFS rate was 98.8% for low-risk patients with high-quality implants versus 92.1% for those with less adequate implants (p < 0.01), and it was 98.3% for intermediate-risk patients with high-quality implants versus 86.4% for those with less adequate implants (p < 0.01).nnnCONCLUSIONSnHigh-quality brachytherapy implants as monotherapy can provide excellent outcomes for men with clinically staged low- and intermediate-risk prostate cancer. For these men, a high-quality implant can achieve results comparable to high-quality surgery in the most favorable pathologically staged patient subgroups.

Erectile function durability following permanent prostate brachytherapy.

PURPOSEnTo evaluate long-term changes in erectile function following prostate brachytherapy.nnnMETHODS AND MATERIALSnThis study included 226 patients with prostate cancer and preimplant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) who underwent brachytherapy in two prospective randomized trials between February 2001 and January 2003. Median follow-up was 6.4 years. Pre- and postbrachytherapy potency was defined as IIEF-6 > or = 13 without pharmacologic or mechanical support. The relationship among clinical, treatment, and dosimetric parameters and erectile function was examined.nnnRESULTSnThe 7-year actuarial rate of potency preservation was 55.6% with median postimplant IIEF of 22 in potent patients. Potent patients were statistically younger (p = 0.014), had a higher preimplant IIEF (p < 0.001), were less likely to be diabetic (p = 0.002), and were more likely to report nocturnal erections (p = 0.008). Potency preservation in men with baseline IIEF scores of 29-30, 24-28, 18-23, and 13-17 were 75.5% vs. 73.6%, 51.7% vs. 44.8%, 48.0% vs. 40.0%, and 23.5% vs. 23.5% in 2004 vs. 2008. In multivariate Cox regression analysis, preimplant IIEF, hypertension, diabetes, prostate size, and brachytherapy dose to proximal penis strongly predicted for potency preservation. Impact of proximal penile dose was most pronounced for men with IIEF of 18-23 and aged 60-69. A significant minority of men who developed postimplant impotence ultimately regained erectile function.nnnCONCLUSIONnPotency preservation and median IIEF scores following brachytherapy are durable. Thoughtful dose sparing of proximal penile structures and early penile rehabilitation may further improve these results.

Pretreatment Serum Testosterone and Androgen Deprivation: Effect on Disease Recurrence and Overall Survival in Prostate Cancer Patients Treated With Brachytherapy

PURPOSEnLow testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy.nnnMETHODS AND MATERIALSnFrom October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined for each deceased patient.nnnRESULTSnSix-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075).nnnCONCLUSIONSnLow pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.

Long-term outcomes of prostate cancer patients with Gleason pattern 5 treated with combined brachytherapy and external beam radiotherapy.

PURPOSEnRecent reports have suggested relatively poor prognosis for prostate cancer patients with Gleason pattern 5 treated with dose-escalated external beam radiotherapy (XRT) and androgen deprivation therapy (ADT). We present the largest series of men with high-risk, Gleason pattern 5 prostate cancer treated with permanent interstitial brachytherapy and XRT.nnnMETHODS AND MATERIALSnBetween April 1995 and December 2008, 329 consecutive patients with National Comprehensive Cancer Network high-risk disease were treated with permanent interstitial brachytherapy. Most received XRT and ADT. Median followup was 7.2 years. The cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters.nnnRESULTSnAt 10 years, biochemical progression-free survival, cause-specific survival (CSS), and overall survival for the group of high-risk patients as a whole was 91.1%, 95.5%, and 72.5%, respectively. There was no difference in biochemical progression-free survival between men with and without Gleason pattern 5 (89.7% vs. 91.8%; p=0.56). However, men with Gleason pattern 5 had lower prostate cancer CSS (90.3% vs. 98.1%; p=0.011). There was no difference in overall survival comparing men with and without Gleason pattern 5 disease (67.7% vs. 75.4%; p=0.14).nnnCONCLUSIONSnMen with high-risk, Gleason pattern 5 histology treated with brachytherapy and XRT have excellent long-term outcomes, which compare favorably to dose-escalated XRT/ADT series without brachytherapy. Nonetheless, Gleason pattern 5 results in lower CSS than high-risk disease without Gleason patternxa05.

Relationship between prostate cancer mortality and number of unfavourable risk factors in men treated with definitive brachytherapy

Study Type – Therapy (case series)u2028Level of Evidenceu20034

Factors impacting all-cause mortality in prostate cancer brachytherapy patients with or without androgen deprivation therapy

PURPOSEnCertain subsets of patients have an increased risk of all-cause mortality when androgen deprivation therapy (ADT) is used with definitive radiotherapy. We evaluated the relationship between pretreatment serum testosterone, age, and comorbidities on survival after prostate brachytherapy in men treated with and without ADT.nnnMETHODS AND MATERIALSnFrom October 2001 to September 2005, 803 patients underwent brachytherapy and 720 had a pretreatment serum testosterone. Comorbidities were prospectively recorded for each patient (body mass index>30, hypertension, diabetes, current smoker). Median followup was 5.0 years. 34.2% of the patients received ADT. Focus was on subset of men who might be expected to have more significant side effects associated with ADT.nnnRESULTSnADT did not significantly impact overall survival (OS) in men <65 years, >65 years, with one or no comorbidities, with more than one comorbidity, or with normal/high testosterone level. ADT use in men with low testosterone level was associated with decreased OS (83.6% vs. 93.1%, p=0.01). The adverse impact of ADT in men with low testosterone level was restricted to men with low testosterone level and more than one comorbidity (OS of 71.3% vs. 92.8%, p<0.01), with death from cardiovascular diseases accounting for almost all of the excess mortality. The subset of men with multiple comorbidities and normal/high testosterone level did not experience adverse OS with ADT.nnnCONCLUSIONSnLow pretreatment testosterone level may be a marker for men at increased risk of premature death with ADT. The combination of low pretreatment serum testosterone level and multiple preexisting comorbidities is associated with decreased OS when ADT is incorporated into treatment.