Examining and Comparing the Temporal Changes and Results of Cosmetic, Quality of Life and Patient Satisfaction Achieved With Immediate and Delayed-immediate Implant-based Breast Reconstruction Procedures and Contralateral Symmetrization Techniques

Introduction The indication of total breast removal is primarily the part of a correct oncological therapy, but secondly the removal of the full parenchyma can be prophylactic among high risk patients with positive genetic testing. Unlike in the US, in Europe it is not yet common to perform prophylactic breast surgery on the contralateral side among average risk patients with unilateral breast cancer.

In modern breast surgery, mastectomy means the removal of the entire glandular tissue. Surgery can be done in the absence of contraindication (eg, skin infiltration, mastitis carcinomatosis), by preserving the nipple-areola complex (NAC) and the skin layer above the parenchyma (nipple-sparing mastectomy, NSM) by removal of the whole or a part of the NAC (skin-sparing mastectomy, SSM) or by removal of the nipple but with the preservation of the areola (areola-sparing mastectomy, ASM).

It is important to emphasize that similarly to the classic simplex mastectomy in the cases of SSM, ASM and NSM techniques provided by an experienced and qualified breast surgeon, the complete oncological removal of the mammary gland is done.

The essence of advanced mastectomy techniques is that they ensure the combination of radical oncological resection and immediate (immediate breast reconstruction, IBR) or delayed-immediate breast reconstructive surgery (delayed immediate breast reconstruction, D-IBR) (insertion of a tissue expander during the first operation, then as a second step replace it with a silicone implant). It avoids all the burden and negative effects of distant flap surgery, like donor scars, loss of movements etc.

One or two-step post-mastectomy breast reconstructive surgeries are mainly implant-based techniques and less commonly autologous tissue techniques like distant pedicle flaps or free flaps. The tissue expander or silicone implant is placed primarily in a submuscular position but also can be inserted in a subcutaneous position in front of the large pectoral muscle.

The coverage of the lower pole or even the entire surface of the implant may be strengthened with biological (so-called acellular dermal matrix) or synthetic materials (Ultrapro mesh) to reduce the pressure load of the implant on the preserved skin, the consequent skin perforation and so the loss of the implant.

The international literature of immediate or delayed-immediate postmastectomy breast reconstructive techniques is extensive and the correlation between these procedures and the oncological treatments (such as adjuvant radiotherapy) are well known. According to the currently available evidence, reconstructive techniques do not adversely affect oncological outcome, so these breast surgical techniques are nowadays considered standard procedures in advanced breast cancer surgery.

The immediate or delayed-immediate implant-based reconstruction of the affected breast following skin-sparing mastectomy techniques requires almost in all cases symmetrization of the contralateral breast. Symmetrization surgery involves mastopexy, volume reduction or silicone implant augmentation, or furthermore skin-sparing mastectomy with an implant-based reconstruction corresponding to the tumorous side. Symmetrization can be performed in one step with the tumorous breast surgery or more often at a deferred time.

Postmastectomy breast reconstruction surgeries are well-known as an effective rehabilitation procedures, with significant psycho-oncological benefits to patients with low complication rates and high patient satisfaction. Postmastectomy breast reconstructive surgery however require more sophisticated surgical techniques, special expertise, longer surgical time and significantly higher costs than simplex mastectomies.

The cosmetic results and patient satisfaction achieved with the immediate postmastectomy reconstructive techniques with the use of symmetrisation, are widely studied, and high, mainly in the early postoperative period.

However, the long-term results of the more and more popular and widespread usage of skin-sparing mastectomies, immediate reconstructions and symmetrization surgery and the related patient satisfaction rates have so far not or only barely been in the focus of clinical trials, so the available scientific data is severely limited. The long-term disease-free survival with multidisciplinary treatments in early stage breast cancer could raise up to 85% of patients, so knowing the long-term changes of patient satisfaction, cosmetic result and symmetry of stressful and expensive immediate or delayed-immediate postmastectomy breast reconstruction surgeries is top priority.

Aim of the study

This is a response-adaptive (RAR) prospective randomized study with a long-term follow-up and the aim of this clinical study is to measure with qualitative and quantitative indicators the changes in cosmetic results, quality of life and patient satisfaction after breast reconstructive surgery with silicone implant (following SSM, ASM or NSM mastectomy) and symmetrization (mastopexy and/or silicone implant and/or Ultrapro mesh sling technique) over time.

According to the hypothesis of the study, the results of implant-based breast reconstruction and symmetrization following advanced postmastectomy techniques significantly decrease over time and later results limited patient satisfaction rate.

This is mainly due to the fact that over time, the natural breast differs from the reconstructed breast with silicone implant. Because of the different biological properties (gravity results ptosis on breast with mastopexy, significant volume increasement of the breast with mastopexy due to endocrine therapy, gradually progressive capsular contracture on the tumorous side, nipple flattening, nipple tattoo fading etc.) the two sides change differently resulting in significant asymmetry and consequently could lead to decreased patient satisfaction.

The high degree of asymmetry over time (which can be similar to the difference between the result of a simple mastectomy and natural breast (control group)), may indicates additional surgeries or usage of medical devices, putting a financial burden on the patient and the health system. On the other hand, the symmetry can be achieve with bilateral skin-sparing mastectomies and implant-based immediate or delayed-immediate reconstructions is clearly better and change less with time. The mastectomy of the contralateral disease-free side is considered as an unreasonable burden for moderate risk patients.

The information such as the need for multiple surgeries, change in symmetry over time etc., should be an important part of the professional decision-making mechanism and the surgeon should inform the patient during the primer surgery. Nowadays due to the lack of evidence-based knowledge, it is not part of the patient's information and surgical planning internationally. Planning breast units, attention, capacity and financial resources must also be provided to meet the long-term needs of patients who underwent postmastectomy breast reconstruction. Simple mastectomy with an external prosthesis can be an alternative for patients with intolerable degree of asymmetry or on the contrary, the results may justify the need for bilateral mastectomy and reconstruction even in the absence of high oncological risk and for purely symmetrical and cosmetic reasons.

Patients and method Participation in the study is voluntary. In this response-adaptive (RAR) prospective randomized study, the used standardized surgical techniques are considered to be routine procedures in the literature and iat department as well. The oncological and reconstructive surgeries do not represent new surgical procedures for patients either in their technique nor in the indication, this prospective trial guarantee quantitative and qualitative data collection only. Applied oncological therapies are unaffected by the study and still follows the decisions of the Institute's preoperative and postoperative multidisciplinary breast cancer committee. The study does not change the complex oncological treatment in any way compared to the institute's protocol.

Response-adaptive classification in this study means that the choice of the optimal surgical technique for the patient is not affected by the clinical trial. The selection of the surgical technique is based on the decision-making models that is used for a long time, and made individually for the patient's oncological disease (eg. nipple removal), breast size and degree of ptosis (NSM vs. SSM), which is the same way as patients are treated out-of-study. The principles of selecting symmetrizational techniques are presented in the introduction. In addition, reinforcement with Ultrapro mesh is used during mastopexy when the degree of the breast ptosis is at least Grade 3 or size D according to Regnault's classification or the patient has significant pseudoptosis, so the fibrous system and the skin of the breast have a very loose structure.

Therefore, in a scientific sense, this study does not involve treatments other than routine treatment protocols.

Preoperative examinations:

* Physical examination * Triplet examination of the breast * Chest X-ray * Axillary ultrasound with aspiration cytology if needed * Required additional imaging based on the oncological staging (targeted x-ray, CT, MRI, PET) * Routine hematological and blood test analysis * Measurements of jugulum-nipple width, nipple midline width, and nipple inframammary-fold width * Regnault Classification of breasts' ptosis * Photo documentation (standard 5 directions and ap with raised arms) and the application of the BCCT.core program (regarding data protection regulations) * Filling out the BREAST-Q questionnaire

Recorded data:

Age, body mass, height, BMI, pre-/postoperative cup sizes, presence of preoperative breast assymetry and its severity (BCCT.core software data), past history, medication, smoking habits, oncological data, cTNM, pTN, pathological data, molecular genetic subtype, neoadjuvant and adjuvant therapy, type of axillary treatment, locoregional cancer recurrance, metastasis.

Age, weight, body mass, BMI, skin type typisation (normal, atypical, seborrheals, dehidrated, hyperhydrated (oedamatic)), preoperative cup size, presence of preoperative breast assymetry and its severity (BCCT.core software data), past history, medication, smoking habits, oncological data, cTNM, pTN, pathological data, molecular genetic subtype, type of mastectomy (SM, SSM,ASM, NSM), type of primary reconstruction, neoadjuvant and adjuvant therapy, type of axillary treatment, type of delayed reconstruction, type and time of symmetrisation according to primary surgery, type of the primer surgery, bra cup size after the reconstruction and symmetrisation then measuring it yearly, the size of used silicone implant(s).

Postoperative complications were classified following Clavien-Dindo Classification.

Grade I complication (light inflammations, non-surgical haematoma or suffusion, seroma formation, partial skin/NAC loss, limited fat necrosis, SSI and lymphoedema) does not require medication or surgical treatment. Grade II complication is a Grade I complication that requires medication or surgical interaction (antibiotic therapy, resuture due SSI and multiple puncture due chronic seroma). Grade III complication requires invasive surgical action (haematoma evacuation, chronic inflammation which requires reoperation, severe fat necrosis, full skin/ NAC necrosis and wound dehiscense). Grade IV complication means temporary organ failure. Grade V complication is one that leads to death.

The following data are collected in this trial: preoperative jugulum-nipple width, nipple-midline width, nipple-IMF width, vertical and horizontal width of the areola, Regnault Classification of the breast ptosis then repeating the above measurements during the follow-up (every 6 months) with parallel photo documentation, using BCCT.core program

• Objective cosmetic results [Time frame: up to 5 years]