PSA nadir predicts biochemical recurrence after external beam radiation therapy combined to high dose rate brachytherapy in the treatment of prostate cancer.

INTRODUCTION: Prostate cancer (PCa) is the second most prevalent neoplasm among men in the world. Its treatment has a wide spectrum of alternatives and variables, ranging from active surveillance through radio and/or brachytherapy, to surgery. OBJECTIVE: The present work aimed to identify the predictive factors for biochemical recurrence and to evaluate the toxicity of the treatment using the association of external beam radiation therapy (EBRT) with high dose rate brachytherapy (HDR-BT) applied in the treatment of patients with prostate cancer. METHODS: Longitudinal retrospective study, using a prospectively collected database between 2005 and 2014 of 186 consecutive patients records with a diagnosis of low, intermediate, or high-risk prostate cancer treated with EBRT combined with HDR-BT, in a single medical institution located in the city of Campinas, SP, Brazil (Radium Institute). PSA increase over 2 ng/ml above the nadir PSA was considered as biochemical recurrence, following the definition of the Phoenix Consensus. Continuous and clinically relevant categorical variables (age, initial PSA, delivered dose in EBRT, number of implants, number of positive cores in transrectal biopsy, use of hormone blockade, Gleason score, TNM staging, post treatment PSA and PSA Nadir) were evaluated with absolute (n) and percentage (%) values using multiple logistic regression and validated our previously described optimal PSA nadir as predictor of biochemical recurrence. RESULTS: Post treatment PSA was the only independent predictor of biochemical recurrence, P<0.0001. The lower the PSA nadir the lower the biochemical recurrence risk (P=0.0009). PSA nadir >1 was the best cutoff (P=0.018) determinant of biochemical recurrence. The incidence of grade 3 late toxicity to the genitourinary tract was 0.6%, and there were no cases of severe complications to the gastrointestinal tract. CONCLUSION: External Beam Radiation Therapy conjugated to Brachytherapy in the treatment of Prostate Cancer has demonstrated low biochemical recurrence rates, mainly when PSA nadir <1, with low toxicity into both GU and GI tracts.

T cells CD4+/CD8+ local immune modulation by prostate cancer hemi-cryoablation.

PURPOSE: Tumors escape from the immune system by decreasing CD8+ and increasing CD4+ T cells' activity, druggable targets. Thermal ablation might activate tumor-specific T cells by raising the presentation of tumor-specific antigens and hindering tumor negative immune regulation. Our aim was to assess T cell infiltrate pre- and post-cryoablation in a prospective observational study. METHODS: A total of 240 sextant prostate biopsies cores (12 cores/patient) were collected from 10 unilateral prostate cancer patients (T1c, PSA density < 0.15 ng/dL, Gleason grade group 1, ≤ 2 cancer biopsy cores, and < 50% cancer core involvement) at diagnosis and 12 months after hemi-cryoablation. Cancer-positive (Diag+) and cancer-negative (Diag-) lobes at diagnosis and the same areas 12 months after hemi-cryoablation (Cryo+ and Cryo-, respectively) were explored by immunohistochemistry for infiltrating CD4+ and CD8+ T cells (in 45 random fields per prostate lobe, 400× magnification). The quantitative analysis of cells/mm2 and CD4+/CD8+ ratio were performed and compared among Diag+, Diag-, Cryo+, and Cryo- using ImageJ software. RESULTS: There was a significant increase in tumor-infiltrating CD8+ T cells/mm2 in the Cryo+ tissue (mean, SD 0.31, 0.30) compared to Diag+ (0.18, 0.15), p = 0.015; confirmed in prostate acini (hot spots), p = 0.029, in which infiltrating CD4+/CD8+ T cells' ratio decreased after hemi-cryoablation, p = 0.006. Infiltrating CD4+ T cells/mm2 presented a trend to decrease in Cryo+ (0.26, 0.27) compared to Diag+ (0.38, 0.32). CONCLUSIONS: This is the first study to show local immune modulation after prostate cancer cryoablation, characterized by decreasing CD4+/CD8+ T cells' ratio, potential for clinical impact by unleashing the T-cell response to cancer. Future studies are necessary to explore different energies and longer follow-up clinical endpoints.

Prognostic factors for late urinary toxicity grade 2-3 after conformal radiation therapy on patients with prostate cancer.

OBJECTIVE: Identify prognostic factors associated to late urinary toxicity in patients with prostate cancer submitted to radical conformal radiotherapy (3DCRT). MATERIALS AND METHODS: From July 1997 to January 2002, 285 patients with localized prostate cancer were consecutively treated with 3DCRT and retrospectively analyzed. Thirty seven (13%) patients were submitted to transurethral prostate resection previously to 3DCRT. The median dose delivered to the prostate was 7920 cGy (7020-8460). Patient and treatment characteristics were analyzed and correlated to late urinary toxicity grade 2-3, especially whether certain radiation doses applied to certain bladder volumes, when visualized through computerized tomography (CT) planning, correlated with the observed actuarial incidences of late urinary complications, using bladder volume as a continuous variable. RESULTS: On a median follow-up of 53.6 months (3.6-95.3), the 5-year actuarial free from late urinary toxicity grade 2-3 survival was 91.1%. Seven and fifteen patients presented late urinary toxicity grades 2 and 3, respectively. Prior transurethral resection of prostate and radiation dose over 70 Gy on 30% of initial bladder volume were independent prognostic factors for late urinary toxicity grade 2-3. CONCLUSIONS: This study suggests that restricting radiation doses to 70 Gy or less on 30% of bladder volume, visualized through CT planning, may reduce late urinary complications. It furthermore suggests that patients with prior transurethral resection of prostate may indicate a group of patients with a greater risk for late urinary toxicity grade 2-3 after 3DCRT.

Prognostic factors for late urinary toxicity grade 2-3 after conformal radiation therapy on patients with prostate cancer

OBJECTIVE: Identify prognostic factors associated to late urinary toxicity in patients with prostate cancer submitted to radical conformal radiotherapy (3DCRT) MATERIALS AND METHODS: From July 1997 to January 2002, 285 patients with localized prostate cancer were consecutively treated with 3DCRT and retrospectively analyzed. Thirty seven (13 percent) patients were submitted to transurethral prostate resection previously to 3DCRT. The median dose delivered to the prostate was 7920 cGy (7020-8460). Patient and treatment characteristics were analyzed and correlated to late urinary toxicity grade 2-3, especially whether certain radiation doses applied to certain bladder volumes, when visualized through computerized tomography (CT) planning, correlated with the observed actuarial incidences of late urinary complications, using bladder volume as a continuous variable RESULTS: On a median follow-up of 53.6 months (3.6-95.3), the 5-year actuarial free from late urinary toxicity grade 2-3 survival was 91.1 percent. Seven and fifteen patients presented late urinary toxicity grades 2 and 3, respectively. Prior transurethral resection of prostate and radiation dose over 70 Gy on 30 percent of initial bladder volume were independent prognostic factors for late urinary toxicity grade 2-3 CONCLUSIONS: This study suggests that restricting radiation doses to 70 Gy or less on 30 percent of bladder volume, visualized through CT planning, may reduce late urinary complications. It furthermore suggests that patients with prior transurethral resection of prostate may indicate a group of patients with a greater risk for late urinary toxicity grade 2-3 after 3DCRT.

Salvage conformal radiotherapy for biochemical recurrent prostate cancer after radical prostatectomy.

OBJECTIVE: Assess the results of salvage conformal radiotherapy in patients with biochemical failure after radical prostatectomy and identify prognostic factors for biochemical recurrence and toxicity of the treatment. MATERIALS AND METHODS: From June 1998 to November 2001, 35 patients were submitted to conformal radiotherapy for PSA > or = 0.2 ng/mL in progression after radical prostatectomy and were retrospectively analyzed. The mean dose of radiation in prostatic bed was of 77.4 Gy (68-81). Variables related to the treatment and to tumor were assessed to identify prognostic factors for biochemical recurrence after salvage radiotherapy. RESULTS: The median follow-up was of 55 months (17-83). The actuarial survival rates free of biochemical recurrence and free of metastasis at a distance of 5 years were 79.7% e 84.7%, respectively. The actuarial global survival rate in 5 years was 96.1%. The actuarial survival rate free of biochemical recurrence in 5 years was 83.3% with PSA pre-radiotherapy < or = 1, 100% when > 1 and < or = 2, and 57.1% when > 2 (p = 0.023). Dose > 70 Gy in 30% of the bladder volume implied in more acute urinary toxicity (p = 0.035). The mean time for the development of late urinary toxicity was 21 months (12-51). Dose > 55 Gy in 50%bladder volume implied in more late urinary toxicity (p = 0.018). A patient presented late rectal toxicity of 2nd grade. CONCLUSIONS: Conformal radiotherapy showed to be effective for the control of biochemical recurrence after radical prostatectomy. Patients with pre-therapy PSA < or = 2 ng/mL have more biochemical control.

Salvage conformal radiotherapy for biochemical recurrent prostate cancer after radical prostatectomy

OBJECTIVE: Assess the results of salvage conformal radiotherapy in patients with biochemical failure after radical prostatectomy and identify prognostic factors for biochemical recurrence and toxicity of the treatment. MATERIALS AND METHODS: From June 1998 to November 2001, 35 patients were submitted to conformal radiotherapy for PSA > 0.2 ng/mL in progression after radical prostatectomy and were retrospectively analyzed. The mean dose of radiation in prostatic bed was of 77.4 Gy (68-81). Variables related to the treatment and to tumor were assessed to identify prognostic factors for biochemical recurrence after salvage radiotherapy. RESULTS: The median follow-up was of 55 months (17-83). The actuarial survival rates free of biochemical recurrence and free of metastasis at a distance of 5 years were 79.7 percent e 84.7 percent, respectively. The actuarial global survival rate in 5 years was 96.1 percent.The actuarial survival rate free of biochemical recurrence in 5 years was 83.3 percent with PSA pre-radiotherapy < 1, 100 percent when > 1 and < 2, and 57.1 percent when > 2 (p = 0.023). Dose > 70 Gy in 30 percent of the bladder volume implied in more acute urinary toxicity (p = 0.035). The mean time for the development of late urinary toxicity was 21 months (12-51). Dose > 55 Gy in 50 percent bladder volume implied in more late urinary toxicity (p = 0.018). A patient presented late rectal toxicity of 2nd grade. CONCLUSIONS: Conformal radiotherapy showed to be effective for the control of biochemical recurrence after radical prostatectomy. Patients with pre-therapy PSA < 2 ng/mL have more biochemical control.

Análise da radioterapia com dois tipos de aplicadores ginecológicos no carcinoma do colo do útero: estádio clínico IIb / Analysis of radiotherapy with two types of gynecologic applicators in the carcinoma of the cervix: clinical stage IIb

Estudou-se uma populaçao de 114 pacientes portadoras de carcinoma do colo do útero, est dio clínico IIb, classificaçao pela Federaçao Internacional de Ginecologia e Obstetrícia (FIGO), submetidas a tratamento exclusivo com radioterapia. O diagnóstico foi sempre realizado por biópsia, e o estadiamento clínico compreendeu a utilizaçao dos métodos descritos na classificaçao da FIGO. A idade média da populaçao estudada foi de 54 anos. O tratamento radioterapico foi feito por radioterapia externa e braquiterapia ginecológica. Na radioterapia externa usaram-se dois tipos de equipamentos de megavoltagem: o acelerador linear e a telecobaltoterapia. Na braquiterapia ginecológica, dois tipos de aplicadores foram utilizados: um com o sistema de Fletcher-Suit-Delclos e o outro com o sistema de Henschke. O grupo de Fletcher compreendendo 66 pacientes e o grupo de Henschke, 48 pacientes. A média de idade do grupo de Fletcher foi de 54,5 anos e a do grupo de Henschke de 53,5 anos. Nos dois grupos, foi usada como terapêutica prévia a radioterapia externa pélvica com megavoltagem, enquanto que as sessoes de braquiterapia vieram posteriormente. A sobrevida total em cinco anos, no grupo de Fletcher, foi de 68 por cento e no grupo de Henschke de 44 por cento resultado significativo para o grupo de Fletcher (p = 0,0143179). As complicaçoes foram semelhantes nos dois grupos, donde se conclui que os dois métodos sao reproduzíveis em nosso meio e as pacientes do grupo de Fletcher tiveram um melhor resultado.